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The University of Toledo The University of Toledo Digital Repository Theses and Dissertations 2013 Investigation of the steric and electronic properties of 3-iminophosphine ligands in chelated palladium allyl complexes for use in the regioselective hydroamination of allenes Nicholas Charles Zingales The University of Toledo Follow this and additional works at: http://utdr.utoledo.edu/theses-dissertations Recommended Citation Zingales, Nicholas Charles, "Investigation of the steric and electronic properties of 3-iminophosphine ligands in chelated palladium allyl complexes for use in the regioselective hydroamination of allenes" (2013). Theses and Dissertations. 248. http://utdr.utoledo.edu/theses-dissertations/248 This Thesis is brought to you for free and open access by The University of Toledo Digital Repository. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of The University of Toledo Digital Repository. For more information, please see the repository's About page. A Thesis entitled Investigation of the Steric and Electronic Properties of 3-Iminophosphine Ligands in Chelated Palladium Allyl Complexes for Use in the Regioselective Hydroamination of Allenes by Nicholas Charles Zingales Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Chemistry ____________________________________ Dr. Joseph A.R. Schmidt, Committee Chair ____________________________________ Dr. Mark R. Mason, Committee Member ____________________________________ Dr. Jianglong Zhu, Committee Member ____________________________________ Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo May 2013 Copyright 2013, Nicholas Charles Zingales This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An abstract of Investigation of the Steric and Electronic Properties of 3-Iminophosphine Ligands in Chelated Palladium Allyl Complexes for Use in the Regioselective Hydroamination of Allenes by Nicholas Charles Zingales Submitted to the Graduate Faculty as partial fulfillment of the requirements for the Master of Science Degree in Chemistry The University of Toledo December 2012 A series of (3-iminophosphine)allylpalladium triflate complexes varying in both steric and electronic features was isolated and characterized. The propensity of the complexes in this series to regioselectively catalyze the hydroamination of 3-methyl-1,2butadiene with aryl amines to form solely the kinetic product at room temperature was studied by observing conversion to products via NMR spectroscopy. An understanding of the importance of these 3-iminophosphine ligand features guides the rational design of future catalysts. The 3-iminophosphine ligand composed of di-tert-butyl phosphine, cyclobutene backbone, and tert-butyl imine provided the most active palladium catalyst for this hydroamination when compared to the other complexes in the collection. Larger alicyclic backbone sizes decrease catalytic activity, as does steric hindrance at the imine substituent group. Tertiary aliphatic groups on the phosphorus are necessary for effective catalysis, as primary and secondary aliphatics and aromatic groups also decrease the catalytic activity. Highly basic imine moieties were also shown to decrease catalytic activity. iii Acknowledgments I would like to start of by acknowledging my parents and brother. Without your love and support over the past couple of decades, I don’t think I’d be half the person that I am today. The past three years here while obtaining this degree have helped me to realize all of that. To my folks, I couldn’t have asked for a better upbringing; you taught me as much as you could and then some. Whenever I need advice you are and always have been the first people I think to go to. To Tony, I couldn’t think of a better person to share a room with for those 19 years growing up at home. You work harder than every person I know, including myself, and for this I hope that you succeed in whatever career you end up with at the end of this year. Thank you to all the members of my lab group, especially John, for helping me get through all of the hurtles of my masters, whether it be choosing the best methodology for a reaction or formatting a citation for the tenth time. Thank you to my advisor, Joe, for getting the best out of me that he could and for all the things that he taught me over the last few years. I would also like to thank the University of Toledo for giving me the opportunity to pursue my education here, along with my alma mater John Carroll University for all that its teachers and students taught me over the course of my undergraduate education. Finally I would like to thank the National Science Foundation for funding this research under CHE-0841611. iv Table of Contents Abstract iii Acknowledgments iv Contents v List of Tables vii List of Figures viii List of Schemes ix Chapter 1 A Brief Introduction to Late Transition Metal Catalyzed Hydroamination with an Emphasis on 3-Iminophosphine-Based Palladium Complexes Chapter 2 1.1 The Hydroamination Reaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Proposed Catalytic Mechanisms of Hydroamination . . . . . . . . . . . 2 1.3 Late Transition Metal-Catalyzed Hydroamination . . . . . . . . . . . . . 4 1.4 3-Iminophosphine Based Palladium Hydroamination Catalysts . . 9 Investigation of Steric and Electronic Features of 3Iminophosphine-Based Palladium Hydroamination Catalysts 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 v 2.4 Experimental Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 2.4.1 General Methods and Instrumentation . . . . . . . . . . . . . . . 32 2.4.2 General Procedure for the Catalytic Hydroamination 34 Screening of Compounds 1Pd-10Pd . . . . . . . . . . . . . . . . . . . . 2.4.3 Synthesis and Characterization of Reaction Products . . . 34 2.5 Crystallography of 1Pd, 8Pd, and 9Pd . . . . . . . . . . . . . . . . . . . . . . 47 Chapter 3 Further Modification of the 3-Iminophosphine-Based Palladium Catalyst 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3.2 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 3.4 Experimental Section . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59 3.4.1 General Methods and Instrumentation . . . . . . . . . . . . . . . 59 3.4.2 General Procedure for the Catalytic Hydroamination Screening of Compounds 11Pd-14Pd . . . . . . . . . . . . . . . . . . . 61 3.4.3 Synthesis and Characterization of Reaction Products . . . 62 3.5 Crystallography of 4AgCl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 71 References vi List of Tables 2.1 Comparison between selected 31P and 1H NMR resonances of [(3IP)Pd(allyl)]OTf complexes and their respective free 3IP ligands . . . . . . . 21 2.2 Conversion to product A for the [(3IP)Pd(allyl)]OTf catalyzed hydroamination of 1,1-dimethylallene with aryl amines (complexes 1Pd10Pd) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.3 Crystallographic data for compounds 1Pd, 8Pd, and 9Pd . . . . . . . . . . . . . . . 50 3.1 Comparison between selected 31P and 1H NMR resonances of [(3IP)Pd(allyl)]OTf complexes and their respective free 3IP ligands . . . . . . . 56 3.2 Conversion to product A for the [(3IP)Pd(allyl)]OTf catalyzed hydroamination of 1,1-dimethylallene with aryl amines (complexes 11Pd- 3.3 14Pd) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 Crystallographic data for compound 4AgCl . . . . . . . . . . . . . . . . . . . . . . . . . . 70 vii List of Figures 2-1 3-Iminophosphine (3IP) ligands 1-10 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2-2 ORTEP diagram of 1Pd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2-3 ORTEP diagram of 8Pd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 2-4 ORTEP diagram of 9Pd . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 2-5 ORTEP diagrams of cis and trans isomers of 9Pd . . . . . . . . . . . . . . . . . . . 27 3-1 3-Iminophosphine (3IP) ligands 11-14 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 3-2 ORTEP of 4AgCl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 viii List of Schemes 1-1 Metal catalyzed hydroamination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 1-2 Late-transition metal catalyzed hydroamination of substituted allenes . . . . 6 1-3 [(3-Iminophosphine)Pd(allyl)]OTf catalyzed hydroamination . . . . . . . . . . 10 1-4 Proposed catalytic cycle for the (3IP)allylpalladium triflate catalyzed hydroamination of 1,1-dimethylallene with primary amines . . . . . . . . . . . . 2-1 11 General synthesis of [(3IP)Pd(allyl)]OTf complexes . . . . . . . . . . . . . . . . . . 19 ix Chapter 1 A Brief Introduction to Late Transition Metal Catalyzed Hydroamination with an Emphasis on 3-Iminophosphine-Based Palladium Complexes 1.1 The Hydroamination Reaction Hydroamination is an advantageous method for the preparation of primary, secondary, and tertiary amines due to its 100% atom economy1 and the wide range of regio-, stereo-, and enantioselective metal complexes that are available to catalyze this transformation.2-10 Hydroamination is the addition of an N-H bond of ammonia or of a primary or secondary amine across an unsaturated C-C bond of an alkene, alkyne, or allene. The reaction can take place either intermolecularly at a high entropic demand using affordable and readily obtained substrates or intramolecularly with low entropic demand, but requiring less accessible starting materials. Although hydroamination is slightly exothermic, the direct [2+2] cycloaddition of an N-H bond across a C-C unsaturated bond is orbitally forbidden under thermal conditions, making a catalytic route for this process a virtual necessity.2 1 The pervasive nature of carbon-nitrogen bonds in pharmaceuticals and natural products lends credence to the investigation of new methods of carbon-nitrogen bond formation. Diversification of the hydroamination reaction’s substrate scope will provide key tools for organic chemists to make C-N bond containing products with greater ease and variety, allowing for the use of less reagents, time, and energy, therefore effecting a cost savings in these processes. Similar reactions, such as allylic amination, form small molecule byproducts that decrease their atom economy compared to that of hydroamination.11 Due to their robustness in the presence of oxygen and moisture, as well as their unique reactivity to catalyze the formation of certain products more readily than other metal centers, late transition metal (TM) catalysts have become a significant focus in the field. This product selectivity granted by late transition metal centered catalysts is most likely due to their unique mechanistic nature compared to early and lanthanide metal centered complexes. 1.2 Proposed Catalytic Mechanisms of Hydroamination Late transition metal catalyzed hydroamination has two general postulated mechanisms. One involves the nucleophilic attack of an amine upon the double bond of an η2-alkene or an η3-allyl coordinated to a metal center. The Lewis acidic metal draws electron density away from the double bond, increasing the susceptibility of the bound species to nucleophilic attack (Scheme 1-1 A).2,12,13 The other mechanism involves the coordination of the unsaturated C-C moiety and its insertion into a metal hydride bond, followed by oxidative addition of the amine to the metal center. The newly formed amido 2 and alkyl ligands then undergo reductive elimination, releasing the hydroamination product and reforming the active catalyst (Scheme 1-1 B).2,14,15 Early transition metal hydroamination catalysts typically exist as metal-imido complexes that allow for the [2+2] cycloaddition of an unsaturated C-C bond to an M-N bond to form an azametallacyclobutane ring.2,16,17 After insertion, protolytic cleavage of the M-C bond occurs via one equivalent of amine, followed by a second protolytic cleavage, this time of the M-N bond, releasing the product and reforming the metal-imido catalyst (Scheme 1-1 C). The catalytic mechanism of early transition metal complexes restricts the substrate scope of many early metal centered complexes to primary amines, as secondary amines cannot form the metal-imido intermediate. An alternative mechanism is available for the transformation of secondary amines via early transition metal centered catalysts, though complexes utilizing it are far less common than those that go through the azametallacyclobutane intermediate. Formation of the azametallocyclobutane ring also has a strong effect on the regiochemistry of the nitrogen moiety’s addition; when hydroaminating allenes the nitrogen typically adds to the center carbon of the allene to form an enamine that subsequently rearranges to form an imine,16,18 whereas late transition metal catalysts are able to add the nitrogen to the terminal carbons to maintain the amine and allyl functionalities.3,19-22 Rare-earth metal catalyzed hydroamination is typically limited to the intramolecular variety, but exceptions to this trend are known.2,23 The proposed pathway for this transformation involves the insertion of an unsaturated C-C bond into a metalamido bond, with subsequent protolytic cleavage of the hydroamination product via an equivalent of amine to reform the active catalyst (Scheme 1-1 D).24 3 R" R R' N MLn R' R H2NR" LnM=NR" R R' R" NHR" MLn R' N NHR" C R Scheme 1-1 Metal catalyzed hydroamination. Late transition metal catalyzed hydroamination: Nucleophilic attack A. Late transition metal catalyzed hydroamination: M-H bond insertion B. Early transition metal catalyzed hydroamination: [2+2] Cycloaddition C. Rare-Earth metal catalyzed hydroamination: M-N bond insertion D. Protolytic cleavage of the M-C bond follows to release the hydroamination product, with coordination of the newly formed amido ligand to reform the active catalyst (Scheme 1-1 D). Group (II) and group (XIII) hydroamination catalysts are proposed to proceed through an analogous mechanism to that of the rare-earth metal centered complexes.25,26 1.3 Late Transition Metal-Catalyzed Hydroamination There are numerous late transition metal centered systems for both inter- and intramolecular hydroamination,2,27,28 and because of the favorable properties of these complexes, they will be the focus of further discussion. This group of metals has shown extremely versatile reactivity for catalyzing the hydroamination of a variety of unsaturated C-C bonds including 4 alkenes,14,15,29-40 alkynes,28,41-56 and dienes5,7,12,14,21,22,27,30,32,33,57-71 with a variety of nitrogen containing compounds. Expansion of the substrate scope of the hydroamination reaction is the main driving force of the continued research into the development of new catalysts. Despite a continually developing library of complexes that each catalyze the reaction with a very specific set of substrates, there still remains a need for a general methodology for hydroamination catalysis. Activated dienes (such as conjugated 1,3-dienes and allenes) and alkynes are more readily hydroaminated than alkenes and unactivated dienes, which is reflected in the number of precatalysts published for the catalysis of each of these respective transformations. At first glance, the greater electron density of the sp hybridized carbon of an alkyne may make it seem to be less likely to interact with the electron rich nitrogen moiety during hydroamination than the sp2 hybridized carbon of an alkene, but this is clearly not the case. The negative change in enthalpy (ΔH) is the thermodynamic driving force in all intermolecular hydroamination reactions while retaining an important role in the intramolecular variety of the transformation as well. This change in enthalpy is dependent upon the difference in the heat of formation of the hydroamination products and its reactants, and is greater in magnitude for the transformation of an alkyne to a substituted alkene or imine than it is for the conversion of an alkene to an alkyl amine.72,73 The negative entropy value for intermolecular hydroamination, along with this negative ΔH value (denoting an exothermic reaction), necessitates the use of lower temperatures for effective hydroamination reactions.74 Due to their conjugation and the resonance stabilization of hydroamination intermediates, 1,3-dienes and vinylarenes undergo hydroamination much more readily 5 than other dienes, whose unconjugated pi systems react much more similarly to normal alkenes.2 Nájera,65 Yeh,7 and Toste64 have all recently reported advances in the hydroamination of 1,3-dienes. Nájera showed that a variety of Lewis and Brønsted acids could catalyze intramolecular hydroamination of amines tethered to 1,3-dienes in good to excellent yields with good E:Z stereoselectivity. Yeh used a (Ph 3 P)AuCl catalyst to intramolecularly hydroaminate cyclic 1,3-dienes, while Toste noted improved intramolecular hydroamination enantioselectivity using the chiral alcohol menthol as an additive. Allene hydroamination has grown greatly in popularity over the past few years. Although the intramolecular hydroamination of allenes has been studied briefly,59,60,62,7578 with a focus on enantioselective conversion to products, examples of intermolecular allene hydroamination are more prevalent and include those published by Bertrand,5,21,57 Widenhoefer,20,79,80 Yamamoto,22,58 Toste,12 and Schafer,18,81 as well as our own group.3 Late transition metal catalyzed intermolecular hydroamination of substituted allenes yields two possible regioisomers. Addition of the amino moiety to the substituted carbon terminus of a mono-substituted allene yields a new chiral carbon center and a vinylterminated product, which is typically the kinetic product of these reactions (Scheme 12). Scheme 1-2 Late-transition metal catalyzed hydroamination of substituted allenes. 6 Addition of the amine at the less-substituted carbon atom yields an internal alkene, commonly the thermodynamic product (Scheme 1-2). Regioselective hydroamination of substituted allenes to form the thermodynamic product is much more common and has been accomplished previously with aryl amines and a gold catalyst,20,58 secondary alkylamines and gold21,22 or platinum79 catalysts, ammonia and a gold catalyst,57 and hydrazine with a gold catalyst.5 Also notable is Toste’s mechanistic study involving the hydroamination of a symmetrical allene with methyl carbazate, which demonstrated activation of the allene as the rate-limiting step and implied that there was no coordinated amine in the catalytic mechanism.12 Regioselective intermolecular hydroamination of substituted allenes to form the kinetic (branched) product, though much rarer, has been accomplished via a gold(I) N-heterocyclic carbene complex4 and a rhodium(I) cyclooctadiene chloro dimer.19 Substrate scope was limited to the addition of an Nunsubstituted carbamate in the first example, but the second example was capable of hydroaminating mono-substituted allenes with an array of substituted anilines to the more substituted side of the allene with good enantiomeric excess.4 Alkynes used in hydroamination are typically of the terminal variety,2 affording the Markovnikov selectivity product in good yields with a broad range of amines, including aryl amines,43,44,48-50,82 sulfonamides,45 and alkylamines.44 Hydroamination of internal alkynes, though less common in practice, has regioselectivity that is usually governed by sterics, with the nitrogen moiety adding to the least sterically hindered sp carbon.2,47 Recent exceptions to this trend include work from Zhu, who demonstrated the addition of aniline to the phenyl side of methyl phenylpropiolate,41 while Corma has produced a mixture of Markovnikov and anti-Markovnikov products utilizing both 7 alkylamines and aryl amines, with product selectivity depending upon electronic rather than steric effects.44 Alkenes with high angular strain, such as bicyclic systems like norbornene, react more readily than unstrained pi systems, as the addition of the N-H bond and breakage of the strained double bond create a more relaxed system in the reaction products. Recent examples of norbornene as a substrate for late transition metal catalyzed hydroamination include work done by Tilley83 and Hartwig,15,32 utilizing platinum and iridium catalysts, respectively. Earlier examples of this reaction include those from Brunet84 and Beller,85 each using rhodium to catalyze the reaction. Unstrained alkenes, such as ethylene, have a much less significant thermodynamic driving force towards products when their pi bonds are broken compared to alkynes or bicyclic alkene systems. Very few examples of ethylene hydroamination are present in the literature,2 with the work of Poli and coworkers as a notable exception.86 Poli found that aniline could be added to ethylene with increased product conversions than those previously reported by others34,87 by utilizing aqueous bromide ion to promote the PtBr 2 catalyzed reaction. It was proposed that the bromide anion displaces amine from coordination sites on the metal center, giving the amine more opportunity to attack the ethylene as a nucleophile.34 There are no examples to date that display adequate conversions to hydroaminated ethylene products; amine substrates tend to displace the weakly coordinating ethylene ligand, severely hindering catalysis in all cases.2 Substituted alkenes have found more utility in hydroamination than ethylene, with examples of regio-, stereo-, and enantioselective complexes being used to catalyze their reaction.2,8,34 Cyclic and monosubstituted alkenes are more facilely transformed than 8 heavily substituted, sterically hindered alkenes.2,30,33,34,37 Intramolecular hydroamination of aminoalkenes is more common than the intermolecular transformation and has been shown to provide synthetic routes to a variety of nitrogen containing heterocycles.2 The type of amine used during hydroamination has a significant effect on the success of the reaction. The steric and electronic properties of the amine used determine its readiness to add across the carbon-carbon multiple bond. Highly basic amines, while being predicted to act as good nucleophiles for attack on the unsaturated C-C bond, also tend to irreversibly coordinate to the metal center, competing for precious coordination sites necessary for alkene substrate binding and activation. This almost always results in the “death” of the catalyst, making highly basic amines some of the most difficult substrates to use in hydroamination.2 Amines of less basicity are unlikely to poison the catalyst, but are also less likely to attack as nucleophiles or to coordinate to the metal center in order to participate in further chemical transformations, such as intramolecular proton transfer. Sterically hindered amines govern regioselectivity in many cases, such as with the hydroamination of internal alkenes and alkynes, adding the nitrogen moiety to the least sterically hindered carbon. Steric hindrance can also prevent reaction with many substrates and complexes due to inaccessibility to either coordination sites on the metal center or to the unsaturated carbons under nucleophilic attack. 1.4 3-Iminophosphine-Based Palladium Hydroamination Catalysts To extend upon research in this field and to develop a broader hydroamination substrate scope, the Schmidt Group has contributed multiple 3-iminophosphine (3IP) 9 palladium allyl triflate complexes capable of catalyzing a diverse range of hydroamination reactions (Scheme 1-3). HNRR' HNRR' Ph 2Pd 2Pd NRR' Ph NR' or Ph (R = H) (R = H) HNRR' C HNRR' C H2NR NRR' 5Pd NRR' 5Pd NRR' 4Pd HRN Scheme 1-3 [(3-Iminophosphine)Pd(allyl)]OTf catalyzed hydroamination. The first generation complex, [(2-diphenylphosphinocyclopentene-1-(tert- butyl)imine)Pd(allyl)]OTf (2Pd), was shown to hydroaminate cyclohexadiene and phenyl acetylene with amines of varying pK b values in moderate to good yields.88 These hydroamination products and their yields were not exceptional, but this was the first time that a 3-iminophosphine complex was employed in the catalysis of hydroamination, proving that these new complexes were indeed worthy of further research pursuits. The correlation between amine basicity and hydroamination product yield combined with the 10 lack of acid assisted catalysis also allowed the postulation of an alternative catalytic mechanism to the common unsaturated bond activation and nucleophilic attack of amine pathway proposed by others.2,88 The mechanism proposed by the Schmidt group is summarized in Scheme 1-4 below. Scheme 1-4 Proposed catalytic cycle for the (3IP)allylpalladium triflate catalyzed hydroamination of 1,1-dimethylallene with primary amines. After reductive elimination of the first turnover product of allene (from hydroamination of the allyl ligand), the active catalyst is thought to be a palladium(II) hydride. At this point the allene or diene coordinates to the metal center where it can readily insert into the palladium-hydride bond. The insertion reaction is followed be either an associative or dissociative amine coordination/imine decoordination step. This most likely happens after diene insertion in order to release ring strain of the chelate ring. The imine moiety of the ligand is now rendered more basic, while the amino ligand is now rendered more acidic, allowing the imine lone pair to abstract a proton from the amino ligand, formally 11 changing it into an amido ligand. The amido ligand and the allyl group can then reductively eliminate to form a palladium(0) intermediate that is quickly oxidized back to palladium(II) by protonation from the iminium group, reforming the palladium hydride intermediate and restarting the catalytic cycle. Exploring these 3IP complexes further led to the development of [(2diphenylphosphinocyclohexene-1-(2,6-xylyl)imine)Pd(allyl)]OTf (5Pd). Two key ligand components were varied compared to our first-generation 3IP palladium catalyst, exchanging the tert-butyl imine group for a 2,6-xylyl moiety and the cyclopentene backbone ring for the slightly larger cyclohexene ring. It was hypothesized that the sterically larger xylyl moiety would lead to faster imine decoordination, leading to easier coordination of amine and thus more productive turnover frequency. This second generation complex was found to hydroaminate 1,2- and 1,3-dienes with secondary amines readily. It produced solely the thermodynamic (linear) product when hydroaminating the unsymmetrical 1,1-dimethylallene. It did this much more readily than the first generation 3IP catalyst was capable, hydroaminating 1,1-dimethylallene with morpholine at room temperature in over 98% conversion, whereas the first generation catalyst was only capable of a mixture of kinetic (branched) and thermodynamic products totaling 89% conversion. This was a marked improvement for our catalyst system, which ultimately led to the synthesis of our third generation 3-iminophosphine palladium complex. Our third generation catalyst, [(2-di-tert-butylphosphinocyclopentene-1-(tertbutyl)imine)Pd(allyl)]OTf (4Pd), showed even higher activity for the hydroamination of allenes at room temperature with regioselectivity unobserved for previous complexes 12 synthesized by our group. This complex hydroaminated 1,1-dimethylallene with a sterically and electronically diverse set of anilines to form solely the kinetic (branched) product at room temperature, a catalytic behavior that has yet to be reported by any group but our own with a palladium centered catalyst system. Electron rich anilines were converted to hydroamination products in the greatest conversions, whereas halogenated anilines required mild heating (70 oC) to achieve catalysis. Sterically hindered (orthosubstituted) anilines were not amenable to this reaction. These results further supported the notion that coordination of the amine/decoordination of the imine is an important step in the catalytic cycle. Witnessing extremely varied catalytic behavior from what one would imagine to be the same catalytic system with seemingly inconsequential changes to the ligand, an array of these 3-iminophosphine complexes that varied systematically in their ligand structural features was synthesized, characterized, and screened for their hydroamination catalytic activity. This investigation constitutes the primary investigation discussed in this thesis. 13 Chapter 2 Investigation of Steric and Electronic Features of 3-Iminophosphine-Based Palladium Hydroamination Catalysts 2.1 Introduction Hydroamination is an advantageous method for the preparation of primary, secondary, and tertiary amines due to its 100% atom economy1 and the wide range of regio-, stereo-, and enantioselective metal complexes that are available to catalyze this transformation.2-10 The hydroamination process is characterized by the addition of an NH bond of ammonia or of a primary or secondary amine across an unsaturated C-C bond of an alkene, alkyne, or allene. The reaction can take place either intermolecularly at a high entropic demand using affordable and readily obtained substrates or intramolecularly with low entropic demand, but requiring less accessible starting materials. Although hydroamination is slightly exothermic, the direct [2+2] cycloaddition of an N-H across a C-C unsaturated bond is orbitally forbidden under thermal conditions, making a catalytic route for this process a virtual necessity.2 14 The hydroamination of allenes allows for the synthesis of allylic amines, which can be further transformed using a wide variety of reactions including hydroboration,89 hydroformylation,90 alkene metathesis,91 and heterocycle synthesis.2 Allylic amines also play a major role in the synthesis of pharmaceutical and natural products.92 Early transition metal complexes have been shown to catalyze allene hydroamination with addition of the nitrogen group to the central carbon of the allene and subsequent tautomerization of the resulting enamine to form an imine in the case of primary amine substrates, whereas late transition metal catalysts are known to hydroaminate allenes with addition of the nitrogen moiety to one of the terminal carbons, resulting in retention of the allyl group.2 Intramolecular hydroamination of allenes leads to nitrogen-containing heterocycles. Although intramolecular hydroamination of allenes has been studied briefly,59,60,62,63,75-78 with a focus on enantioselective conversion to products, examples of intermolecular allene hydroamination are more prevalent and include those published by Bertrand,5,21,57 Widenhoefer,20,79,80 Yamamoto,22,58 Toste,12 and Schafer,18,81 as well as our own group.3,71 Late transition metal catalyzed intermolecular hydroamination of substituted allenes yields two possible regioisomers. Addition of the amino moiety to the substituted carbon terminus of a mono-substituted allene yields a new chiral carbon center and a vinyl-terminated product, which is typically the kinetic product of these reactions (Scheme 1-2). Addition of the amine at the less-substituted carbon atom yields an internal alkene, commonly the thermodynamic product (Scheme 1-2). Regioselective hydroamination of substituted allenes to form the thermodynamic product is much more common and has been accomplished previously with aryl amines and a gold catalyst,20,58 secondary alkylamines and gold21,22 or platinum79 catalysts, ammonia and a gold 15 catalyst,57 and hydrazine with a gold catalyst.5 Also notable is Toste’s mechanistic study involving the hydroamination of a symmetrical allene with methyl carbazate, which demonstrated activation of the allene as the rate-limiting step and implied that there was no coordinated amine in the catalytic mechanism.12 Regioselective intermolecular hydroamination of substituted allenes to form the kinetic (branched) product, though much rarer, has been accomplished via a gold(I) N-heterocyclic carbene complex, although substrate scope was limited to the addition of an N-unsubstituted carbamate,4 as well as with a rhodium(I) Josiphos complex that was able to add a series of anilines enantioselectively to the more substituted side of the allene.19 The development of new catalysts capable of producing the branched product in these reactions would be considerably advantageous in order to expand upon this limited substrate scope and to allow a much larger variety of allylic amines to be synthesized via hydroamination. Also of interest is the development of more cost-effective metal catalysts, as gold, platinum, and rhodium are among the most expensive of the transition metals. Synthesized previously in our group were 3-iminophosphine (3IP) ligands 2,88 4,3 and 571 (Figure 2-1), as well as their respective [(3IP)Pd(allyl)]OTf complexes 2Pd,88 4Pd,3 and 5Pd.71 2Pd was shown to hydroaminate phenylacetylene and 1,3cyclohexadiene in moderate yields,88 whereas 5Pd was shown to hydroaminate 3-methyl1,2-butadiene (1,1-dimethylallene) and 2,3-dimethyl-1,3-butadiene with secondary alkylamines regioselectively to form the thermodynamic (linear) products in moderate to excellent yields.71 The most significant advance in the development of these catalysts came with the discovery of 4Pd, which was found to regiospecifically hydroaminate 1,1dimethylallene using a variety of aryl amines (anilines) to form solely the kinetic 16 (branched) products in good to excellent yields.3 Because the observed catalysis of these three different ligand frameworks varied dramatically, it was hypothesized that the specific steric and electronic features of the ligand were responsible for the greatly varying catalytic activity. Unfortunately, in the development of our hydroamination catalysts (2Pd, 4Pd, and 5Pd), the ligand framework was not altered in a systematic fashion, but rather involved changes to two ligand components with each new catalyst explored. Figure 2-1 3-Iminophosphine (3IP) ligands 1-10. Thus, the catalytic data generated with our three previously published [(3IP)Pd(allyl)]OTf complexes was insufficient in determining which alterations to ligand design were critical in order to optimize catalytic activity. As a means to address this deficiency, synthesized herein is an array of eight [(3IP)Pd(allyl)]OTf complexes with systematic variance of the steric and electronic features of the 3IP ligands. Each palladium complex was screened for catalytic activity in the hydroamination of 1,1 17 dimethylallene with a selection of seven aryl amines spanning a wide range of steric and electronic parameters. Also reported herein is the synthesis of two additional ligands and their respective [(3IP)Pd(allyl)]OTf complexes whose designs were based upon the results of the catalytic screening of the original array of eight complexes. 2.2 Results and Discussion The effectiveness of 3-iminophosphine (3IP) allylpalladium triflate complexes as catalysts for the hydroamination of 1,3-dienes, allenes, and alkynes with primary and secondary amines has been shown previously.71 These results implied that the steric and electronic properties of the 3IP supporting ligands have a significant effect on the rates observed in hydroamination catalysis. These ligand properties can be governed via substitution of three tunable domains: the size of the alicyclic backbone and the substituent groups of the imine and phosphine moieties. For example, cyclic ketones that vary in ring size can be reacted with the Vilsmeier-Haack reagent, various amines can be used for the Schiff base condensation, and phosphination can be completed with different di-substituted lithium phosphides in the synthesis of these ligands (Scheme 2-1). Our previous reports detail the synthesis and isolation of ligands 2,88 4,3 and 5,71 as well as their respective allyl palladium triflate complexes 2Pd,88 4Pd,3 and 5Pd.71 Unfortunately, the ligands described in our previous reports varied two tunable domains with each catalyst improvement. The synthesis of complexes with systematic variation of the three tunable domains would allow for correlation of catalytic activity with each domain involved in ligand construction. 18 Scheme 2-1 General synthesis of [(3IP)Pd(allyl)]OTf complexes. (n = 1-4, R’ = tBu or 2,6-dimethylphenyl, R” = tBu or Ph) (i) 2 eq. DMF, 1.6 eq. POCl 3 , 0 oC, 4 hours then 55 oC, 14 hours; 0 oC, NaHCO 3 ; (ii) 1.3 eq. H 2 NR’, pentane, 4 Å molecular sieves, 0 oC; (iii) 1.6 eq. LiPR” 2 , Et 2 O, 3 hours, RT. Thus, in the current contribution, we set out to produce a complete series of 3IP ligands utilizing both backbone ring sizes (cyclopentenyl and cyclohexenyl), imines (tert-butyl and 2,6-xylyl), and phosphines (tert-butyl and phenyl) to determine the impact of each unit on catalytic activity (1-8, Figure 2-1). Then, by use of the palladium complexes of these eight ligands in catalysis, we hoped that an empirical understanding of the effectiveness of these ligand components would allow for the rational design of improved hydroamination catalysts. Compounds 1, 3, and 6 were synthesized using procedures analogous to those for 3-iminophosphines 2,88 4,3 and 5,71 respectively, while ligands 7, 8, 9, and 10 required 19 significant modifications to the experimental methodology (Scheme 2-1). The main change involved the dropwise addition of a dilute solution of lithium di-tertbutylphosphide in diethyl ether to a rapidly stirred solution of the selected chloroimine in diethyl ether at ambient temperature. The attempted use of our previous synthetic procedures consistently resulted in multiple unidentifiable phosphorus containing products that were inseparable from both the target ligand and the final palladium complex. Overall, the syntheses of ligands 7-10 were especially sensitive, requiring the purest of starting materials. Chloroaldehyde of high purity was produced via neat reaction of the cyclic ketone with the Vilsmeier-Haack reagent (Scheme 2-1), under a nitrogen atmosphere using degassed reagents. After reacting for 14 h at 55 oC, the resulting solution was made basic and extracted with pentane, in contrast to diethyl ether as cited previously.88 This improved methodology, analogous to that of Paquette,93 is vital for achieving reaction completion and ensuring chloroaldehyde purity, as well as improving product stability at both low and ambient temperatures. Prior to its use, lithium di-tertbutylphosphide was recrystallized from diethyl ether and rinsed with pentane to minimize highly reactive impurities that were found to complicate phosphination of the various chloroimines, leading to multiple unidentifiable phosphorus containing products. Ligand coordination and ion exchange reactions yielding the final [(3IP)Pd(allyl)]OTf complexes proceeded analogously to Beck and Schmidt3 (Scheme 2-1) with only slight workup modifications. Specifically, the intermediate 3IP allylpalladium chloride complex was rinsed of excess ligand before treatment with silver triflate because we have found that byproduct silver chloride is readily coordinated by excess 3IP ligand. Furthermore, toluene was excluded from the anion exchange step, as its presence seems to destabilize 20 the palladium complex, resulting in presumed palladium(0) byproducts that were not soluble in the readily available solvents. All of the ligands and palladium complexes described in this chapter are diamagnetic, and so an analysis of their NMR spectroscopic features proves quite insightful. As one would anticipate, substantial differences were noted between 1H, 13C, and 31 P NMR spectra of the free 3-iminophosphine ligands and those of the [(3IP)Pd(allyl)]OTf complexes. Further differences were evident when comparing ligands and their respective complexes with di-tert-butylphosphino moieties to those possessing diphenylphosphino moieties. Downfield shifts in the 31 P NMR signals were observed upon coordination of the ligand to the palladium, with a further downfield shift upon chloride abstraction (Table 2.1). Table 2.1 Comparison between selected 31P and 1H NMR resonances of [(3IP)Pd(allyl)]OTf complexes and their respective free 3IP ligands (all values in ppm). 3IPb Δ31P δ 3IPPda 3IPb Δ1H δ 3IPPda 31 1 1 Pδ Pδ R'N=CH H δ R'N=CH H δ 13.11 -23.20 36.31 7.88 8.64 -0.76 1 16.90 -24.70 41.60 7.94 8.72 -0.78 2 59.48 13.24 46.24 7.84 8.82 -0.98 3 61.80 13.20 48.60 8.06 8.88 -0.82 4 25.20 -12.60 37.80 7.70 9.05 -1.35 5 31.78 -12.70 44.48 7.65 9.09 -1.44 6 71.63 20.05 51.58 7.65 9.32 -1.67 7 75.37 19.98 55.39 7.85 9.37 -1.52 8 80.64 24.81 55.83 8.07 9.37 -1.30 9 55.18 11.36 43.82 7.94 8.27 -0.33 10 a b 3IPPd refers to [(3IP)Pd(allyl)]OTf complex. 3IP refers to uncoordinated ligand. 31 The absolute change in ppm for the 31P NMR signal between free ligands and the target [(3IP)Pd(allyl)]OTf complexes (Δ31Pδ) varied greatly depending on the ligand used. Δ31Pδ was always larger for complexes with larger backbone size while holding 21 phosphine and imine substituents constant. Also, in every case complexes with di-tertbutylphosphino moieties had larger Δ31Pδ values than the corresponding complexes with diphenylphosphino moieties. Furthermore, all 31 P NMR resonances for complexes and ligands with di-tert-butylphosphino moieties were located further downfield than those of the corresponding diphenylphosphino moieties. Keeping imine and phosphine moieties constant, all complexes with larger backbone sizes displayed signals that were also located further downfield than those with smaller backbone sizes. These 31 P NMR spectroscopic trends imply that the phosphorus of the ligand is more tightly bound to the metal for the larger backbone rings and for the di-tert-butylphosphino complexes. All 1H NMR resonances for the imine C-H of the palladium complexes rested at or slightly below 8 ppm, an upfield shift from that of the free ligands, which were typically found around 9 ppm. Ligand 10 displayed a significantly upfield imine proton resonance compared to the rest of the free ligands. It also showed the smallest change in 1H NMR resonance (Δ1Hδ) upon coordination to form complex 10Pd, with a mere -0.33 ppm shift (the negative number denoting an upfield shift from ligand to triflated complex). The other species shifted from -0.76 to -1.67 ppm upon formation of the triflate complexes. In general, the upfield shift in the imine proton resonance can be attributed to reduction in the carbon-nitrogen double bond character upon coordination of the imine lone pair to palladium. A smaller than normal upfield shift correlates to a smaller loss of double bond character consistent with weaker imine nitrogen coordination to palladium. Thus, it seems that ligand 10 binds less strongly to the metal center through its imine nitrogen atom than the other ligands in this series. The trends in the 13 C NMR spectra parallel those of the 1H NMR spectra, as there are significant changes in the chemical shift of the 22 imine carbon between free and coordinated ligands. The terminal carbons of the allyl ligands (cis and trans to phosphorus) were readily differentiated based upon both the magnitude of the J P-C coupling constant, and their relative chemical shift values. The trans carbon was typically located downfield from the cis carbon and displayed a J P-C coupling constant an order of magnitude larger. Many of the palladium allyl triflate complexes (1Pd, 2Pd,88 4Pd,3 5Pd,71 8Pd, and 9Pd) were structurally characterized via X-ray crystallography. In all cases, X-ray quality single crystals were grown from pentane-layered THF solutions at -25 oC. Each complex had an outer-sphere triflate anion with palladium’s coordination sphere occupied by the chelating 3-iminophosphine ligand and a single 3η-allyl group, producing a distorted square planar geometry. Structures of 1Pd (Figure 2-2) and 5Pd,71 differing only in the size of the alicyclic backbone, both exhibited disorder in their allyl ligands to the extent that no discernable comparison could be made between their bite angles. The series of three complexes with tert-butyl groups on both nitrogen and phosphorus, but with variation of the backbone size from five to seven carbon atoms, varied less dramatically in bite angle and seemed more dependent on the position of the allyl group relative to that of the alicyclic backbone. Viewing the molecule along the P-Pd-N plane, an allyl group pointing in the direction of the backbone is denoted as cis while one pointing in the opposite direction is denoted as trans. Complex 4Pd exists as the trans isomer, 8Pd exists as the cis isomer (Figure 2-3), and 9Pd has both the cis and trans isomers in its asymmetric unit (Figures 2-4 and 2-5). 23 Figure 2-2. ORTEP (50% thermal ellipsoids) of 1Pd. Triflate anion and hydrogen atoms have been omitted for clarity. Selected bond lengths (in Å): Pd1-P1 = 2.2680(8), Pd1-N1 = 2.101(2), Pd1-C27 = 2.104(3), Pd1-C29 = 2.236(3), P1-C6 = 1.799(3), C1-C2 = 1.458(4), C2-C6 = 1.346(4), N1-C1 = 1.275(4). Bond angles (in deg): P1-Pd1-N1 = 95.11(7), C27-Pd1-C29 = 67.5(1), N1-Pd1-C27 = 168.7(1), N1Pd1-C29 = 101.3(1), P1-Pd1-C27 = 96.15(9), P1-Pd1-C29 = 163.59(9), Pd1-P1-C6 = 110.7(1), P1-C6-C2 = 125.6(2), C1-C2-C6 = 130.5(3), N1-C1-C2 = 128.2(3), Pd1N1-C1 = 129.4(2). 24 Figure 2-3. ORTEP (50% thermal ellipsoids) of 8Pd. Triflate anion, disordered tertbutyl carbons, and hydrogen atoms have been omitted for clarity. Selected bond lengths (in Å): Pd1-P1 = 2.332(2), Pd1-N1 = 2.116(6), Pd1-C12 = 2.208(8), Pd1C14 = 2.146(7), P1-C1 = 1.844(7), C1-C6 = 1.35(1), C6-C7 = 1.49(1), N1-C7 = 1.26(1). Bond angles (in deg): P1-Pd1-N1 = 89.8(2), C12-Pd1-C14 = 66.1(4), N1Pd1-C12 = 100.7(3), N1-Pd1-C14 = 165.3(3), P1-Pd1-C12 = 165.4(2), P1-Pd1-C14 = 104.4(2), Pd1-P1-C1 = 101.7(2), P1-C1-C6 = 122.1(6), C1-C6-C7 = 126.5(7), N1C7-C6 = 129.8(7), Pd1-N1-C7 = 121.6(5). 25 Figure 2-4 ORTEP diagram (50% thermal ellipsoids) of trans-9Pd (top view). Triflate anion and hydrogen atoms have been omitted for clarity. Selected bond lengths (in Å): Pd1-P1 = 2.331(1), Pd1-N1 = 2.098(4), Pd1-C21 = 2.162(5), Pd1C23 = 2.257(5), P1-C3 = 1.845(5), C1-C2 = 1.472(6), C2-C3 = 1.361(6), N1-C1 = 1.288(6). Bond angles (in deg): P1-Pd1-N1 = 92.1(1), C21-Pd1-C23 = 66.4(2), N1Pd1-C21 = 166.8(2), N1-Pd1-C23 = 101.5(2), P1-Pd1-C21 = 100.9(1), P1-Pd1-C23 = 162.5(1), Pd1-P1-C3 = 109.1(2), P1-C3-C2 = 122.4(4), C1-C2-C3 = 126.2(4), N1C1-C2 = 131.7(4), Pd1-N1-C1 = 123.2(3). 26 N2 Pd2 P2 P1 Pd1 N1 Figure 2-5 ORTEP diagrams (50% thermal ellipsoids) of cis (top) and trans (bottom) isomers of 9Pd (side views). Triflate anion, hydrogen atoms, and tert-butyl groups have been omitted for clarity. 27 Those with the trans relationship had more strained bite angles, i.e. 4Pd at 92.52(6)o and trans-9Pd at 92.1(1)o, while the cis complexes 8Pd and cis-9Pd had bite angles of 89.8(2)o and 90.1(1)o, respectively. Again, the cyclopentenyl complex (4Pd) deviated the most from the ideal 90o bite angle. Complex 2Pd, which is a hybrid of the two series, has a bite angle of 92.9(5)o, very close to that of 4Pd, most likely due to its similar trans configuration. This may also indicate that the imine’s substituent group is more significant in determining the angle than those of the phosphine. All Pd-N distances varied little, whereas Pd-P distances were generally shorter for diphenylphosphino moieties (~2.27 Å) than for di-tert-butylphosphino moieties (~2.33 Å), which likely reflects the larger steric bulk of the tert-butyl groups. Similar disubstituted bidentate phosphine palladium complexes show similar Pd-P bond distance patterns.94,95 In our most recent report, compound 4Pd was shown to readily catalyze the hydroamination of 1,1-dimethylallene with primary aryl amines (anilines) to form exclusively the kinetic (terminal alkene) products at room temperature (Product A; Table 2).3 Sterically hindered anilines prevented hydroamination in all cases, while halogenated anilines required heating to a temperature of 70 oC in order to achieve appreciable conversion to product. In an effort to more fully understand this reactivity, to improve upon the catalytic performance of 4Pd, and to test our previously reported complexes 2Pd88 and 5Pd71 in allene hydroamination, the complete array of ligands 1-8 and their respective complexes 1Pd-8Pd was synthesized. All eight palladium complexes were then tested in the hydroamination of 1,1-dimethylallene with a selection of seven anilines displaying diverse steric and electronic properties (Table 2.2). 28 The results generated by screening these eight palladium complexes were generally disappointing, as most of these complexes showed no catalytic turnover for the hydroamination of 1,1-dimethylallene with anilines. From this array, only our previously reported 4Pd was found to catalyze this hydroamination effectively. Complex 2Pd also catalyzed the reaction, albeit with extremely poor conversions compared to that of 4Pd. Complexes 2Pd and 4Pd are very similar, differing only in the substituent groups of their phosphine moieties. The phosphine tert-butyl groups of 4Pd seem to play a vital role in its catalytic activity, as substituting them with phenyl groups in 2Pd virtually eliminated catalytic activity. Table 2.2 Conversion to product A for the [(3IP)Pd(allyl)]OTf catalyzed hydroamination of 1,1-dimethylallene with aryl amines (complexes 1Pd-10Pd). Conversion was monitored via 1H NMR spectroscopy. Aniline 1Pd 2Pd 3Pd 4Pd 5Pd 6Pd 7Pd 8Pd 9Pd 10Pd -- -- -- 60% -- -- -- -- -- 91% -- -- -- -- -- -- -- 6% -- 92% -- -- -- -- >95% -- -- -- -- >95% -- -- -- -- 90% -- -- 6% -- 72% 2-Me -----Aniline 3-Me -13% ->95% -Aniline 4-Me -16% ->95% -Aniline 4-tBu -17% -88% -Aniline 4-F -9% -65%* -Aniline 3-OMe -12% -62% -Aniline * indicates reaction at 70oC. “--” indicates <5%. 29 Changing the tert-butyl group of the imine moiety into the quite sterically-hindered 2,6dimethylphenyl group resulted in complete loss of catalytic activity in all four complexes containing that substituent (1Pd, 3Pd, 5Pd, 7Pd). Furthermore, increasing the backbone ring size to a cyclohexene ring also destroyed catalytic activity across the series of complexes (see 5Pd-8Pd). Overall, as is so often noted in catalyst design, a very specific set of features (found in 4Pd) were crucial to achieve catalysis, with minor changes having a devastating impact on catalytic activity. Despite the fact that no improved catalysts were discovered upon screening the array of 1Pd-8Pd, we were convinced that this method would yield an improved catalyst and so further investigation into ligand design was undertaken. The results observed for complexes 1Pd-8Pd necessitated that further ligand designs incorporate tert-butyl groups on both the phosphine and imine moieties of the 3IP ligands. Believing that the conformational stability of the cyclohexene ring was the downfall of 8Pd when compared to the less stable cyclopentene ring of 4Pd, ligand 9 and complex 9Pd (each bearing a cycloheptenyl ring) were synthesized. Unfortunately, the conformational effects of the cycloheptene ring of 9Pd did not grant any greater catalytic performance than that of the cyclohexene ring. Thus, we explored the opposite approach, utilizing the smaller and highly strained cyclobutenyl ring, leading to the synthesis of 10 and 10Pd. The smaller alicyclic ring size of 10Pd significantly enhanced catalytic activity, producing the same regiospecific product as 4Pd, but at higher conversions for virtually every substrate and at lower temperature for those that had required heating with 4Pd. Most notably, 10Pd catalyzed the reaction of 4-fluoroaniline with 1,1-dimethylallene at room temperature to give 90% conversion, as compared to the 65% conversion at 70 oC when using 4Pd. 30 Also, the reaction of unsubstituted aniline was also significantly improved, converting 91% of substrate to product, a 31% increase over that previously reported.3 Due to the superior performance of 10Pd compared to all of the other 3IP complexes investigated thus far, it is clear that the size of the alicyclic ring is a critical component in the design of [(3IP)Pd(allyl)]OTf catalysts, with the cyclobutenyl backbone proving to be preferred over larger ring sizes. 2.3 Conclusions A collection of ten [(3IP)Pd(allyl)]OTf complexes was investigated in the catalytic hydroamination of 1,1-dimethylallene with electronically and sterically diverse aryl amines. There is a strong correlation between the three tunable ligand structural domains and the catalytic activity of these complexes. The ligand composed of di-tertbutyl phosphine, cyclobutenyl backbone, and tert-butyl imine domains led to the most active palladium catalyst when compared to the other ligands in this collection. Better electron donating substituents on the phosphine and imine moieties grant greater catalytic ability to these complexes while larger alicyclic backbone ring sizes almost completely eliminate catalytic activity. Excellent regiospecific hydroamination of 1,1-dimethylallene is now attainable for all but the most sterically hindered anilines. Further refinement of the 3IP ligand set, including investigation into the effects of phosphine and imine moieties of even greater electron donating character is ongoing. Additionally, use of these palladium complexes in other catalytic transformations, as well as one-pot multistep syntheses, continues to be under investigation in our laboratory. 31 2.4 Experimental Section 2.4.1 General Methods and Instrumentation Alicyclic α,β-unsaturated β-chloroaldehydes and β-chloroimines were synthesized under ambient atmospheric conditions. All other manipulations were performed under an inert N 2 atmosphere using standard Schlenk and drybox techniques. Solvents were predried prior to use; methylene chloride was passed through two columns of 4 Å molecular sieves and degassed with nitrogen. Pentane, diethyl ether, and toluene were passed through columns of activated alumina and 4 Å molecular sieves and degassed with nitrogen. Tetrahydrofuran was distilled from sodium metal and degassed with nitrogen. n-Butyllithium (1.6 M in hexanes), (allyl)palladium(II) chloride dimer, diphenylchlorophosphine, ditert-butylchlorophosphine, lithium aluminum hydride, and silver triflate were purchased from Strem and used without further purification. Phosphorus oxychloride, tert-butylamine, 2,6-dimethyl aniline, and cyclopentanone were purchased from Acros and used without further purification. Cyclohexanone, 1,1dimethylallene and cycloheptanone were purchased from Alfa Aesar and used without further purification. Cyclobutanone was purchased from Sigma Aldrich and used without further purification. Dimethylformamide was purchased from BDH and stored over 4 Å molecular sieves. Anilines were purchased from Sigma-Aldrich or another commercial source and dried over calcium hydride, either neat (liquid anilines) or as solutions in methylene chloride (solid anilines). Liquid anilines were freeze-pump-thawed three times and vacuum distilled. Solutions of solid anilines in methylene chloride were freezepump-thawed three times, filtered, and the methylene chloride removed via reduced pressure. CDCl 3 was purchased from Cambridge Isotope Laboratories, vacuum 32 transferred from CaH 2 , and stored over 4 Å molecular sieves. Benzene-d 6 was also purchased from Cambridge Isotope Laboratories, vacuum transferred from sodium metal, and stored over 4 Å molecular sieves. Silica gel (Porosity: 60 Å, Particle size: 40-63 μm) was purchased from Sorbent Technologies and used as received. 1H and 13 C NMR data were obtained on a 600 MHz Inova or 400 MHz VXRS NMR spectrometer at ambient temperature at 599.9 MHz for 1H NMR and 150.8 MHz for 13C NMR and 399.95 MHz for 1H NMR and 100.56 MHz for 13 C NMR, respectively. All 31 P NMR spectra were collected on a 400 MHz VXRS NMR spectrometer at ambient temperature at 161.90 MHz. All spectra were taken using C 6 D 6 or CDCl 3 as the NMR solvent. 1H NMR shifts are given relative to the residual solvent resonances at 7.16 and 7.26 ppm, respectively, and 13C NMR shifts are given relative to the residual solvent peak of CDCl 3 (77.36 ppm). 31 P NMR spectra were externally referenced to 0.00 ppm with 5% H 3 PO 4 in D 2 O. IR samples were prepared as Nujol mulls and taken between KBr plates on a Perkin-Elmer XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point (Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at the Ohio Crystallographic Consortium, housed at The University of Toledo. Elemental analyses were determined by Atlantic Microlab, Inc., Norcross, GA or Galbraith Laboratories, Inc., Knoxville, TN. High resolution mass spectrometry using electrospray ionization was performed at the University of Illinois Mass Spectrometry Laboratory, Urbana, IL. 33 2.4.2 General Procedure for the Catalytic Hydroamination Screening of Compounds 1Pd-10Pd All manipulations were performed under an N 2 atmosphere. 3-Methyl-1,2butadiene (68 mg, 1 mmol) was added to a mixture of amine (0.5 mmol), [(3IP)Pd(allyl)]OTf complex (5 mol%), and deuterated benzene (0.8 ml). Conversion to products was monitored via 1H NMR spectroscopy. Hydroamination products formed were reported previously.3 2.4.3 Synthesis and Characterization of Reaction Products The following compounds were synthesized as previously reported: LiPPh 2 ,88 LiPtBu 2 ,3 2-chlorocyclopentenecarboxaldehyde,88 2-chlorocyclohexenecarboxaldehyde,71 2- chlorocyclohexene-1-(2,6-xylyl)imine,71 2-chlorocyclopentene-1-(tert-butyl)imine,88 2diphenylphosphinocyclopentene-1-(tert-butyl)imine (2),88 2-di-tert- butylphosphinocyclopentene-1-(tert-butyl)imine (4),3 2-diphenylphosphinocyclohexene1-(2,6-xylyl)imine (5),71 butyl)imine)Pd(allyl)]OTf (2Pd),88 butyl)imine)Pd(allyl)]OTf (4Pd),3 [(2-diphenylphosphinocyclopentene-1-(tert[(2-di-tert-butylphosphinocyclopentene-1-(tertand [(2-diphenylphosphinocyclohexene-1-(2,6- xylyl)imine)Pd(allyl)]OTf (5Pd).71 Alicyclic α,β-Unsaturated β-Chloroaldehydes The following was performed with degassed reagents and solvents, and an atmosphere of nitrogen was maintained over the mixture as the reaction proceeded. Dimethylformamide (9.00 g, 123 mmol) was cooled to 0 oC. POCl 3 (15.00 g, 97 mmol) was then added 34 dropwise with rapid stirring. Formation of the Vilsmeier-Haack reagent was allowed to proceed for 4 h, slowly warming to room temperature. The reagent was again cooled to 0 o C before dropwise addition of the respective cyclic ketone (61 mmol). After slowly warming to room temperature, the mixture was heated at 55 oC for 14 h. The crude reaction mixture was quenched over water at 0 oC to produce the chloroaldehyde. The mixture was made basic with an excess of sodium bicarbonate before extracting into pentane (4 × 100 ml). The organic layer was rinsed with water and brine and dried over magnesium sulfate for 20 min. The organic layer had ethyl acetate added up to 2% and was passed through a plug of silica. Solvent was evaporated to yield the final product as a lightly colored liquid. Alicyclic α,β-Unsaturated β-Chloroimines tert-Butyl imines To pentane (20 ml) was added activated 4 Å molecular sieves. This was cooled to 0 oC before adding freshly prepared chloroaldehyde and 1.3 equivalents of tert-butylamine. The reaction was allowed to proceed for 14 h, slowly warming to ambient temperature. Magnesium sulfate was added to the reaction mixture and allowed to stir for 20 min before filtering over celite. Diethyl ether and excess tert-butylamine were evaporated, yielding the final product. 2,6-Dimethyl phenyl imines To pentane (20 ml) was added activated 4 Å molecular sieves. This was cooled to 0 oC before adding freshly prepared chloroaldehyde and 1.3 equivalents of 2,6- 35 dimethylaniline. The reaction was stirred for 96 h, slowly warming to ambient temperature. Magnesium sulfate was added to the reaction mixture and allowed to stir for 20 min before filtering over celite. Diethyl ether was evaporated and the product redissolved in pentane. Ethyl acetate was added up to 2% and the product solution was passed through a plug of silica to remove excess aniline. Solvent was evaporated, yielding the final product. 3-Iminophosphine Ligands Unless otherwise noted, all 3-iminophosphine ligands were prepared via the following methodology. To a Schlenk tube with attached addition funnel was added degassed chloroimine (1 equiv) and diethyl ether (15 ml). Lithium di-tert-butylphosphide (1.6 equiv) was dissolved in diethyl ether (30 ml) in a separate flask. The lithium phosphide was transferred to the addition funnel and then added dropwise to the rapidly stirring chloroimine solution at ambient temperature over a time period of 1 h. The reaction was allowed to stir for an additional 2 h before concentration in vacuo to an approximate volume of 10 ml. At this time, pentane (20 ml) was added to help precipitate excess lithium phosphide. The supernatant was separated via cannula filtration, solvent removed in vacuo, and the resulting oil triturated with pentane (2 × 10 ml). The oil was then extracted into pentane (2 × 20 ml) and passed through a celite padded frit. Solvent was again removed in vacuo to yield the final product. 36 (3-Iminophosphine)allylpalladium Triflate Complexes Solutions of both ligand (1.05 equiv) and allylpalladium chloride dimer (0.5 equiv) in dichloromethane (10 ml each) were combined at ambient temperature and allowed to stir for 14 h. Solvent was removed in vacuo, and the crude solid was triturated and rinsed with pentane (10 ml each). The solid was redissolved in methylene chloride (10 ml) and added to a slurry of silver triflate (0.65 equiv) in methylene chloride (10 ml) and stirred in the dark for 14 h. The crude reaction mixture was then passed through a thick pad of celite, and solvent removed in vacuo. The resulting solid was triturated with pentane (10 ml), dissolved in a minimal amount of tetrahydrofuran, layered with pentane, and cooled to -20 oC to promote crystal growth. 2-Chlorocycloheptenecarboxaldehyde: light yellow liquid (6.128 g, 63.18%); 1H NMR (CDCl 3 ): δ 10.11 (s, 1H), 2.83-2.80 (m, 2H), 2.49-2.47 (m, 2H), 1.80-1.76 (m, 2H), 1.71-1.65 (m, 2H), 1.49-1.43 (m, 2H); 13 C{1H- NMR (CDCl 3 ): δ 191.1, 156.6, 138.7, 41.9, 31.8, 25.7, 25.1, 24.9; IR: 3331 (w), 2926 (s), 2854 (s), 2740 (w), 2698 (w), 1737 (s), 1675 (s), 1638 (s), 1607 (s), 1446 (s), 1389 (m), 1373 (m), 1337 (m), 1239 (s), 1218 (s), 1140 (s), 1083 (m), 1062 (s), 1047 (m), 1016 (m), 974 (s), 959 (s), 907 (m), 886 (m), 829 (m), 808 (m), 761 (s), 689 (s) cm-1. 2-Chlorocyclobutenecarboxaldehyde: light yellow liquid (1.39 g, 19.3%); 1H NMR (CDCl 3 ): δ 9.69 (s, 1H), 2.85 (t, 3J H-H = 3.6 Hz, 2H), 2.65 (t, 3J H-H = 3.6 Hz, 2H); 13 C{1H} NMR (CDCl 3 ): δ 183.8, 143.3, 141.5, 35.4, 25.1; IR: 3326 (m), 2978 (s), 2945 (s), 2815 (m), 2717 (w), 1782 (m), 1722 (s), 37 1673 (s), 1607 (s), 1439 (m), 1417 (m), 1373 (s), 1286 (s), 1210 (s), 1112 (s), 965 (s), 878 (m), 791 (w), 769 (m), 731 (s) cm-1. 2-Chlorocyclopentene-1-(2,6-xylyl)imine: orange-red liquid (3.563 g, 95.77%); 1H NMR (CDCl 3 ): δ 8.23 (s, 1H), 7.05 (d, 3J H-H = 7.8 Hz, 2H), 6.94 (t, 3J H-H = 7.8 Hz, 1H), 2.86 (td, 3J H-H = 7.8 Hz, 2J H-H = 2.1 Hz, 1H), 2.85 (td, 3J H-H = 7.8 Hz, 2J H-H = 2.4 Hz, 1H), 2.82 (td, 3J H-H = 7.8 Hz, 2J H-H = 2.1 Hz, 1H), 2.81 (td, 3J H-H = 7.8 Hz, 2J H-H = 2.4 Hz, 1H), 2.12 (s, 6H), 1.96 (pent, 3J H-H = 7.8 Hz, 2H); 13C{1H} NMR (CDCl 3 ): δ 157.6, 151.4, 141.7, 135.8, 128.2, 127.9, 124.0, 39.9, 30.5, 20.9, 18.6; IR: 3062 (w), 3020 (w), 2957 (s), 2915 (s), 2852 (m), 2727 (w), 2360 (w), 2035 (w), 1918 (w), 1839 (w), 1724 (w), 1656 (m), 1625 (s), 1609 (s), 1593 (s), 1467 (s), 1441 (m), 1378 (m), 1347 (m), 1274 (m), 1247 (m), 1190 (s), 1158 (w), 1090 (m), 1033 (w), 985 (w), 938 (m), 912 (w), 844 (m), 760 (s), 723 (m), 671 (w) cm-1. 2-Chlorocyclohexene-1-(tert-butyl)imine: yellow-orange liquid (1.626 g, 81.30%); 1H NMR (CDCl 3 ): δ 8.46 (s, 1H), 2.50-2.46 (m, 2H), 2.42-2.38 (m, 2H), 1.77-1.71 (m, 2H), 1.68-1.62 (m, 2H), 1.21 (s, 9H); 13C{1H} NMR (CDCl 3 ): δ 154.2, 138.7, 131.7, 57.4, 35.2, 29.8, 26.0, 23.7, 21.8; IR: 2964 (s), 2932 (s), 2859 (s), 2356 (w), 2324 (w), 1717 (w), 1691 (w), 1623 (m), 1560 (w), 1455 (w), 1434 (w), 1366 (m), 1266 (w), 1240 (w), 1209 (m), 1172 (w), 1135 (w), 1115 (w), 1099 (w), 1072 (w), 1025 (w), 989 (m), 957 (w), 905 (w), 868 (w), 826 (w), 779 (w), 695 (w) cm-1. 38 2-Chlorocycloheptene-1-(tert-butyl)imine: light yellow liquid (3.640 g, 50.97%); 1H NMR (CDCl 3 ): δ 8.37 (s, 1H), 2.74-2.71 (m, 2H), 2.67-2.64 (m, 2H), 1.77-1.75 (m, 2H), 1.65-1.62 (m, 2H), 1.50-1.47 (m, 2H), 1.21 (s, 9H); 13C{1H} NMR (CDCl 3 ): δ 155.0, 142.8, 137.4, 57.7, 40.7, 32.0, 30.3, 26.9, 26.1, 25.5; IR: 3217 (w), 2968 (s), 2926 (s), 2698 (w), 1737 (w), 1680 (m), 1618 (s), 1446 (s), 1368 (s), 1332 (m), 1280 (m), 1259 (s), 1213 (s), 1140 (m), 1099 (m), 1083 (m), 1062 (m), 1016 (w), 974 (s), 959 (s), 922 (m), 901 (s), 876 (w), 829 (m), 808 (w), 761 (s), 684 (m), 626 (m) cm-1. 2-Chlorocyclobutene-1-(tert-butyl)imine: yellow liquid (0.833 g, 40.7%); 1H NMR (CDCl 3 ): δ 7.94 (s, 1H), 2.74-2.73 (m, 2H), 2.66-2.64 (m, 2H), 1.20 (s, 9H); 13 C{1H} NMR (CDCl 3 ): δ 147.4, 141.2, 130.3, 57.9, 34.7, 29.9, 26.0; IR: 3196 (w), 2967 (s), 2935 (s), 2869 (m), 1787 (w), 1673 (m), 1646 (s), 1607 (m), 1515 (w), 1466 (m), 1422 (w), 1390 (w), 1362 (s), 1335 (m), 1297 (m), 1259 (s), 1205 (s), 1112 (s), 1096 (m), 1020 (m), 976 (s), 954 (m), 894 (m), 878 (m), 802 (m), 785 (m), 731 (m), 573 (s) cm-1. 2-Diphenylphosphinocyclopentene-1-(2,6-xylyl)imine (1): Prepared in a manner analogous to Shaffer et al.88 yellow-orange solid (0.618 g, 61.8%); mp 99-100°C; 1H NMR (CDCl 3 ): δ 8.64 (d, 4J P-H = 3.6 Hz, 1H), 7.38-7.34 (m, 10H), 7.00 (d, 3J H-H = 7.8 Hz, 2H), 6.90 (t, 3J H-H = 7.8 Hz, 1H), 3.03-3.00 (m, 2H), 2.46-2.44 (m, 2H), 2.04 (s, 6H), 1.96 (pseudo pent, 3J H-H = 7.8 Hz, 3J H-H = 7.2 Hz, 2H); 13C{1H} NMR (CDCl 3 ): δ 159.8 (d, 3J P-C = 22.0 Hz), 153.1 (d, 39 2 J P-C = 21.4 Hz), 151.7, 150.2 (d, 1J P-C = 22.6 Hz), 136.5 (d, 1J P-C = 8.7 Hz), 133.4 (d, 2 J P-C = 19.4 Hz), 129.0, 128.8 (d, 3J P-C = 6.9 Hz), 128.2, 127.2, 123.8, 38.1 (d, 3J P-C = 4.4 Hz), 34.0 (d, 2J P-C = 5.4 Hz), 22.7 (d, 3J P-C = 2.0 Hz), 18.5; 31P{1H} NMR (CDCl 3 ): δ 23.20; IR: 2961 (s), 2919 (s), 2857 (s), 2720 (w), 1612 (m), 1586 (w), 1455 (s), 1376 (m), 1298 (w), 1240 (w), 1193 (m), 1156 (w), 1088 (w), 1025 (w), 999 (w), 968 (w), 915 (w), 842 (w), 764 (m), 738 (m), 722 (m), 696 (m) cm-1. HRMS (m/z): [M+H]+ calcd for C 26 H 27 NP 384.1882, HRMS found: 384.1874. 2-Di-tert-butylphosphinocyclopentene-1-(2,6-xylyl)imine (3): Prepared in a manner analogous to that of Beck et al.3 deep red oil (0.910 g, 75.8%); 1H NMR (CDCl 3 ): δ 8.82 (d, 4J P-H = 5.4 Hz, 1H), 7.00 (d, 3 J H-H = 7.8 Hz, 2H), 6.89 (t, 3J H-H = 7.8 Hz, 1H), 2.98-2.95 (m, 2H), 2.88-2.85 (m, 2H), 2.07 (s, 6H), 1.99-1.96 (m, 2H), 1.19 (d, 3J P-H = 11.4 Hz, 18H); 13C{1H} NMR (CDCl 3 ): δ 161.5 (d, 3J P-C = 29.9 Hz), 156.2 (d, 2J P-C = 20.7 Hz), 152.1, 151.9 (d, 1J P-C = 36.5 Hz), 128.1, 127.1, 123.6, 40.1 (d, 2J P-C = 6.5 Hz), 32.9 (d, 3J P-C = 5.7 Hz), 32.6 (d, 1J P-C = 19.9 Hz), 31.1 (d, 2J P-C = 14.3 Hz), 23.9, 18.7; 31P{1H} NMR (CDCl 3 ): δ 13.24; IR: 2945 (s), 2853 (s), 1608 (s), 1466 (s), 1360 (m), 1324 (m), 1254 (m), 1190 (m), 1169 (m), 1084 (m), 1062 (m), 1013 (m), 843 (w), 801 (m), 758 (s), 716 (w) cm-1. HRMS (m/z): [M+H]+ calcd for C 22 H 35 NP 344.2507, HRMS found: 344.2509. 40 2-Diphenylphosphinocyclohexene-1-(tert-butyl)imine (6): Prepared in a manner analogous to that of Kuchenbeiser et al.71 off-white liquid (0.824 g, 82.4%); 1H NMR (CDCl 3 ): δ 9.09 (d, 4J P-H = 3.6 Hz, 1H), 7.387.32 (m, 10H), 2.56-2.53 (m, 2H), 1.90-1.88 (m, 2H), 1.66-1.63 (m, 2H), 1.58-1.56 (m, 2H), 1.13 (s, 9H); 13C{1H} NMR (CDCl 3 ): δ 156.4 (d, 3J P-C = 40.2 Hz), 147.6 (d, 2J P-C = 17.7 Hz), 140.7 (d, 1J P-C = 20.4 Hz), 136.7 (d, 1J P-C = 10.8 Hz), 133.6 (d, 2J P-C = 18.9 Hz), 128.6 (d, 3J P-C = 6.3 Hz), 128.6, 57.7, 30.2 (d, 3J P-C = 3.6 Hz), 30.1, 27.0 (d, 2J P-C = 5.8 Hz), 23.7, 22.3; 31P{1H} NMR (CDCl 3 ): δ -12.70; IR: 3126 (w), 3054 (w), 2962 (s), 2921 (s), 2849 (m), 2664 (w), 2274 (w), 1952 (w), 1885 (w), 1814 (w), 1757 (w), 1618 (s), 1582 (w), 1475 (w), 1448 (w), 1428 (s), 1362 (m), 1326 (w), 1305 (w), 1259 (m), 1202 (s), 1090 (m), 1064 (m), 1023 (m), 961 (w), 900 (w), 843 (w), 802 (m), 740 (s), 694 (s) cm-1. HRMS (m/z): [M+H]+ calcd for C 23 H 29 NP 350.2038, found 350.2043. 2-Di-tert-butylphosphinocyclohexene-1-(2,6-xylyl)imine (7): bright yellow solid (1.100 g, 91.67%); mp 90-91 oC; 1H NMR (CDCl 3 ): δ 9.32 (d, 4J P-H = 9.6 Hz, 1H), 7.01 (d, 3J H-H = 7.2 Hz, 2H), 6.89 (t, 3J H-H = 7.2 Hz, 1H), 2.72-2.70 (m, 2H), 2.66 (br s, 2H), 2.08 (s, 6H), 1.79-1.77 (m, 2H), 1.72-1.69 (m, 2H), 1.21 (d, 3J P-H = 11.4 Hz, 18H); 13C{1H} NMR (CDCl 3 ): δ 164.5 (d, 3J P-C = 48.9 Hz), 151.9, 149.0 (d, 2J P-C = 18.6 Hz), 148.4 (d, 1J P-C = 36.8 Hz), 127.7, 126.9, 123.0, 32.6 (d, 1J P-C = 24.1 Hz), 32.1 (d, 3J P-C = 5.0 Hz), 31.1 (d, 2J P-C = 15.1 Hz), 26.6 (d, 2J P-C = 6.5 Hz), 23.1, 22.2, 18.4; 31 P{1H} NMR (CDCl 3 ): δ 20.05; IR: 2926 (s), 2854 (s), 1612 (w), 1592 (w), 1462 (s), 1379 (m), 1259 (w), 1197 (w), 1171 (w), 1088 (w), 1016 (w), 844 (w), 803 (w), 761 (w), 720 (w) cm-1. HRMS (m/z): [M+H]+ calcd for C 23 H 37 NP 358.2664, found 358.2656. 41 2-Di-tert-butylphosphinocyclohexene-1-(tert-butyl)imine (8): light brown liquid (0.715 g, 71.5%); 1H NMR (CDCl 3 ): δ 9.37 (d, 4J P-H = 10.8 Hz, 1H), 2.58-2.56 (m, 2H), 2.50-2.48 (m, 2H), 1.68-1.59 (m, 4H), 1.20 (d, 3J P-H = 7.2 Hz, 18H), 1.19 (s, 9H); 13C{1H} NMR (CDCl 3 ): δ 159.2 (d, 3J P-C = 47.1 Hz), 149.5 (d, 2J P-C = 18.1 Hz), 144.1 (d, 1J P-C = 35.4 Hz), 57.4 (d, 5J P-C = 1.4 Hz), 32.2 (d, 3J P-C = 5.0 Hz), 31.4 (d, 2 J P-C = 14.9 Hz), 31.0 (d, 1J P-C = 15.2 Hz), 30.4, 27.5 (d, 2J P-C = 5.0 Hz), 23.5, 22.6; 31 P{1H} NMR (CDCl 3 ): δ 19.98; IR: 2926 (s), 2854 (s), 1618 (m), 1462 (s), 1363 (s), 1259 (m), 1202 (m), 1171 (m), 1088 (m), 1016 (m), 964 (w), 901 (w), 803 (m), 720 (w) cm-1. HRMS (m/z): [M+H]+ calcd for C 19 H 37 NP 310.2664, found 310.2659. 2-Di-tert-butylphosphinocycloheptene-1-(tert-butyl)imine (9): yellow oil (0.540 g, 61.6%); 1H NMR (CDCl 3 ): δ 9.37 (d, 4J P-H = 10.8 Hz, 1H), 2.77-2.71 (m, 4H), 1.78-1.75 (m, 2H), 1.62-1.59 (m, 2H), 1.45-1.43 (m, 2H), 1.20 (s, 9H), 1.18 (d, 3 J P-H = 12.0 Hz, 18H); 13 C{1H} NMR (CDCl 3 ): δ 159.4 (d, 3J P-C = 48.6 Hz), 157.3 (d, 2 J P-C = 18.3 Hz), 149.6 (d, 1J P-C = 36.8 Hz), 57.4 (d, 5J P-C = 1.4 Hz), 35.5 (d, 3J P-C = 5.6 Hz), 33.4 (d, 1J P-C = 24.7 Hz), 32.9, 31.4 (d, 2J P-C = 15.2 Hz), 30.5, 29.4 (d, 2J P-C = 6.8 Hz), 28.1, 26.3; 31P{1H} NMR (CDCl 3 ): δ 24.81; IR: 2916 (s), 2854 (s), 1612 (m), 1462 (s), 1363 (s), 1259 (m), 1213 (m), 1171 (m), 1088 (w), 1016 (m), 959 (w), 876 (w), 808 (m) cm-1. HRMS (m/z): [M+H]+ calcd for C 20 H 39 NP 324.2820, found 324.2817. 2-Di-tert-butylphosphinocyclobutene-1-(tert-butyl)imine (10): brown oil (0.365 g, 68.9%); 1H NMR (CDCl 3 ): δ 8.27 (d, 4J P-H = 2.0 Hz, 1H), 2.87-2.86 (m, 4H), 1.20 (s, 9H), 1.19 (d, 3J P-H = 11.6 Hz, 18H); 13C{1H} NMR (CDCl 3 ): δ 159.1 (d, 42 3 J P-C = 21.6 Hz), 151.4 (d, 1J P-C = 39.8 Hz), 151.0 (d, 2J P-C = 5.3 Hz), 57.7, 33.4 (d, 1J P-C = 4.7 Hz), 33.0 (d, 2J P-C = 16.5 Hz), 30.7 (d, 2J P-C = 13.3 Hz), 30.1, 29.4 (d, 3J P-C = 11.4 Hz); 31P{1H} NMR (CDCl 3 ): δ 11.36; IR: 2956 (s), 2869 (m), 1628 (w), 1571 (w), 1529 (w), 1472 (m), 1389 (m), 1363 (m), 1259 (s), 1213 (m), 1192 (m), 1176 (m), 1093 (s), 1021 (s), 865 (m), 803 (s), 663 (m) cm-1. HRMS (m/z): [M+H]+ calcd for C 17 H 33 NP 282.2351. found 282.2351. [(2-Diphenylphosphinocyclopentene-1-(2,6-xylyl)imine)Pd(allyl)]OTf (1Pd): yellow solid (0.154 g, 92.1%); mp 191 oC dec; 1H NMR (CDCl 3 ): δ 7.88 (d, 4J P-H = 2.4 Hz, 1H), 7.58-7.55 (m, 8H), 7.51-7.48 (m, 2H), 7.11-7.05 (m, 3H), 5.81-5.77 (m, 1H), 3.66-3.62 (m, 1H), 3.55-3.50 (m, 1H), 3.49 (d, 3J H-H = 2.4 Hz, 1H), 3.11-3.04 (m, 2H), 2.70 (d, 3J H-H = 12.0 Hz, 1H), 2.65-2.57 (m, 2H), 2.21 (s, 3H), 2.14-2.08 (m, 2H), 2.10 (s, 3H); 13 C{1H} NMR (CDCl 3 ): δ 164.4 (d, 3J P-C = 7.2 Hz), 155.8, 153.0 (d, 2J P-C = 17.2 Hz), 137.8 (d, 1J P-C = 32.6 Hz), 133.2 (d, 4J P-C = 13.6 Hz), 132.8 (d, 4J P-C = 13.1 Hz), 132.4 (d, 2J P-C = 24.3 Hz), 130.2 (d, 3J P-C = 10.7 Hz), 130.17 (d, 3J P-C = 10.9 Hz), 129.2, 129.0, 128.6 (d, 1J P-C = 50.1 Hz), 128.2 (d, 1J P-C = 49.8 Hz), 127.3, 123.9 (d, 2J P-C = 5.9 Hz), 122.4, 120.2, 87.1 (d, 2J P-C = 28.4 Hz), 55.0 (d, 2J P-C = 3.5 Hz), 39.0 (d, 2J P-C = 11.3 Hz), 36.5, 22.4 (d, 3J P-C = 5.4 Hz), 18.9, 18.8; 31P{1H} NMR (CDCl 3 ): δ 13.11; IR: 2926 (s), 2854 (s), 2719 (w), 2677 (w), 1462 (s), 1379 (s), 1301 (w), 1259 (w), 1218 (w), 1145 (w), 1093 (w), 1031 (w), 969 (w), 798 (w), 720 (w), 637 (w) cm-1. Anal. Calcd for C 30 H 31 F 3 NO 3 PPdS: C, 52.99; H, 4.60; N, 2.06. Found: C, 52.99; H, 4.57; N, 2.17. 43 [(2-Di-tert-butylphosphinocyclopentene-1-(2,6-xylyl)imine)Pd(allyl)]OTf (3Pd): dark brown solid (0.736 g, 61.5%); mp 131 oC dec; 1H NMR (CDCl 3 ): δ 7.84 (d, 4J P-H = 1.2 Hz, 1H), 7.14-7.07 (m, 3H), 5.69-5.64 (m, 1H), 4.16 (d, 3J H-H = 6.6 Hz, 1H), 3.583.54 (m, 1H), 3.18-3.15 (m, 2H), 3.10-3.08 (m, 1H), 2.95-2.90 (m, 2H), 2.77 (d, 3J H-H = 12.6 Hz, 1H), 2.20 (s, 3H), 2.12-2.07 (m, 2H), 2.09 (s, 3H), 1.44 (d, 3J P-H = 15.6 Hz, 9H), 1.34 (d, 3J P-H = 15.6 Hz, 9H); 13C{1H} NMR (CDCl 3 ): δ 164.7 (d, 3J P-C = 6.2 Hz), 157.5, 153.3 (d, 2J P-C = 11.9 Hz), 140.2 (d, 1J P-C = 15.8 Hz), 129.2, 128.9, 127.3, 127.1, 126.9, 121.8 (d, 2J P-C = 5.4 Hz), 88.7 (d, 2J P-C = 26.5 Hz), 53.1 (d, 2J P-C = 2.7 Hz), 41.1 (d, 3J P-C = 2.1 Hz), 38.7 (d, 2J P-C = 10.0 Hz), 38.6 (d, 1J P-C = 15.8 Hz), 38.3 (d, 1J P-C = 16.0 Hz), 31.0 (d, 2J P-C = 6.2 Hz), 30.7 (d, 2J P-C = 6.5 Hz), 24.0 (d, 3J P-C = 3.6 Hz), 18.8; 31P{1H} NMR (CDCl 3 ): δ 59.48; IR: 2926 (s), 2854 (s), 2719 (w), 1612 (w), 1566 (w), 1457 (s), 1379 (s), 1270 (w), 1140 (w), 1083 (w), 1026 (w), 720 (w), 637 (m) cm-1. Anal. Calcd for C 26 H 39 F 3 NO 3 PPdS: C, 48.79; H, 6.14; N, 2.19. Found: C, 48.88; H, 6.07; N, 2.33. [(2-Diphenylphosphinocyclohexene-1-(tert-butyl)imine)Pd(allyl)]OTf (6Pd): light brown solid (0.340 g, 85.1%); mp 160 oC dec; 1H NMR (CDCl 3 ): δ 7.65 (d, 4J P-H = 3.6 Hz, 1H), 7.51 (br s, 6H), 7.34-7.33 (m, 4H), 5.77-5.70 (m, 1H), 4.90-4.87 (m, 1H), 3.89-3.85 (m, 1H), 3.39 (s, 1H), 2.96 (d, 3J P-H = 10.8 Hz, 1H), 2.56 (s, 2H), 1.85-1.81 (m, 4H), 1.73-1.64 (m, 2H), 1.14 (s, 9H); 13 C{1H} NMR (CDCl 3 ): δ 163.9 (d, 3J P-C = 11.5 Hz), 148.8 (d, 2J P-C = 12.2 Hz), 133.3, 132.1 (d, 4J P-C = 31.5 Hz), 129.8 (d, 2J P-C = 19.6 Hz), 129.3 (d, 1J P-C = 32.9 Hz), 127.8 (d, 1J P-C = 45.7 Hz), 121.0 (d, 2J PC = 6.5 Hz), 80.7 (d, 2J P-C = 31.1 Hz), 64.3, 56.9 (d, 2J P-C = 4.8 Hz), 31.6 (d, 2J P-C = 9.8 Hz), 30.4, 29.9, 22.5 (d, 3J P-C = 4.5 Hz), 21.5; 31 P{1H} NMR (CDCl 3 ): δ 31.78; IR: 2916 (s), 2854 (s), 44 2719 (m), 2667 (m), 1628 (w), 1586 (w), 1457 (s), 1379 (s), 1259 (s), 1145 (m), 1099 (m), 1026 (m), 974 (m), 912 (m), 798 (m), 720 (m), 637 (m) cm-1. Anal. Calcd for C 27 H 33 F 3 NO 3 PPdS•1/2(C 4 H 8 O): C, 51.07; H, 5.47; N, 2.05. Found: C, 51.14; H, 5.44; N, 2.08. [(2-Di-tert-butylphosphinocyclohexene-1-(2,6-xylyl)imine)Pd(allyl)]OTf (7Pd): dark brown solid (0.483 g, 36.5%); mp 155-160 oC dec; 1H NMR (CDCl 3 ): δ 7.65 (s, 1H), 7.15-7.08 (m, 3H), 5.69-5.64 (m, 1H), 4.13 (d, 3J H-H = 6.6 Hz, 1H), 3.54-3.50 (m, 1H), 3.12-3.09 (m, 1H), 2.89-2.86 (m, 1H), 2.79 (d, 3J H-H = 12.6 Hz, 1H), 2.75-2.72 (m, 1H), 2.65-2.56 (m, 2H), 2.22 (s, 3H), 2.12 (s, 3H), 1.87-1.81 (m, 4H), 1.49 (d, 3J P-H = 15.6 Hz, 9H), 1.39 (d, 3J P-H = 15.0 Hz, 9H); 13C{1H} NMR (CDCl 3 ): δ 169.0 (d, 3J P-C = 8.6 Hz), 158.1, 146.7 (d, 2J P-C = 7.8 Hz), 139.4 (d, 1J P-C = 13.1 Hz), 129.4, 129.0, 127.3, 127.1, 126.8, 122.0 (d, 2J P-C = 5.4 Hz), 88.0 (d, 2J P-C = 26.2 Hz), 55.1 (d, 2J P-C = 3.9 Hz), 39.5 (d, 1J P-C = 13.1 Hz), 38.8 (d, 1J P-C = 13.9 Hz), 35.7 (d, 2J P-C = 8.7 Hz), 32.9 (d, 3J P-C = 2.9 Hz), 31.8 (d, 2J P-C = 6.6 Hz), 31.4 (d, 2J P-C = 6.9 Hz), 21.8 (d, 3J P-C = 2.3 Hz), 21.4 (d, 4J P-C = 1.2 Hz), 18.9; 31P{1H} NMR (CDCl 3 ): δ 71.63; IR: 2916 (s), 2854 (s), 1618 (w), 1560 (w), 1457 (s), 1379 (s), 1270 (s), 1223 (m), 1140 (m), 1031 (m), 912 (w), 798 (w), 720 (w), 637 (m) cm-1. Anal. Calcd for C 27 H 41 F 3 NO 3 PPdS: C, 49.58; H, 6.32; N, 2.14. Found: C, 49.58; H, 6.37; N, 2.16. [(2-Di-tert-butylphosphinocyclohexene-1-(tert-butyl)imine)Pd(allyl)]OTf (8Pd): green-brown solid (0.706 g, 53.0%); mp 105 oC dec; 1H NMR (CDCl 3 ): δ 7.85 (d, 4J P-H = 3.0 Hz, 1H), 5.64-5.57 (m, 1H), 5.08-5.05 (m, 1H), 3.91 (d, 3J H-H = 7.2 Hz, 1H), 3.79- 45 3.76 (m, 1H), 2.82 (d, 3J H-H = 12.0 Hz, 1H), 2.57-2.56 (m, 4H), 1.78-1.67 (m, 4H), 1.45 (s, 9H), 1.45 (d, 3J P-H = 14.4 Hz, 9H), 1.36 (d, 3J P-H = 14.4 Hz, 9H); 13 C{1H} NMR (CDCl 3 ): δ 166.9 (d, 3J P-C = 9.2 Hz), 149.5 (d, 2J P-C = 9.8 Hz), 132.4 (d, 1J P-C = 12.8 Hz), 119.6 (d, 2J P-C = 5.6 Hz), 82.4 (d, 2J P-C = 26.7 Hz), 65.4, 56.6, 38.6 (d, 1J P-C = 10.9 Hz), 38.6 (d, 1J P-C = 11.3 Hz), 34.4 (d, 2J P-C = 9.5 Hz), 32.4 (d, 3J P-C = 2.1 Hz), 31.9 (d, 2J P-C = 6.2 Hz), 31.7 (d, 2J P-C = 6.5 Hz), 30.7, 22.7 (d, 3J P-C = 2.3 Hz), 21.5; 31 P{1H} NMR (CDCl 3 ): δ 75.37; IR: 2926 (s), 2854 (s), 1462 (s), 1379 (m), 1265 (m), 1145 (w), 1031 (w), 798 (w), 720 (w), 637 (m) cm-1. Anal. Calcd for C 23 H 41 F 3 NO 3 PPdS: C, 45.59; H, 6.82; N, 2.31. Found: C, 45.65; H, 6.85; N, 2.51. [(2-Di-tert-butylphosphinocycloheptene-1-(tert-butyl)imine)Pd(allyl)]OTf (9Pd): light yellow solid (0.322 g, 62.0%); mp 149-154 oC dec; 1H NMR (CDCl 3 ): δ 8.07 (d, 4 J P-H = 2.4 Hz, 1H), 5.63-5.57 (m, 1H), 5.22-5.19 (m, 1H), 3.93 (d, 3J H-H = 7.2 Hz, 1H), 3.89-3.85 (m, 1H), 2.98-2.88 (m, 2H), 2.79-2.68 (m, 3H), 1.92-1.88 (m, 1H), 1.86-1.81 (m, 1H), 1.78-1.72 (m, 2H), 1.55-1.48 (m, 2H), 1.45 (s, 9H), 1.43 (d, 3J P-H = 14.4 Hz, 9H), 1.33 (d, 3J P-H = 15.0 Hz, 9H); 13 C{1H} NMR (CDCl 3 ): δ 167.8 (d, 3J P-C = 10.0 Hz), 156.8 (d, 2J P-C = 9.8 Hz), 156.1 (d, 1J P-C = 13.7 Hz), 119.7 (d, 2J P-C = 5.4 Hz), 85.1 (d, 2 J P-C = 26.1 Hz), 65.7, 54.2 (d, 2J P-C = 4.1 Hz), 39.4 (d, 1J P-C = 13.3 Hz), 38.8 (d, 1J P-C = 10.9 Hz), 38.6 (d, 2J P-C = 11.6 Hz), 34.5 (d, 3J P-C = 2.0 Hz), 31.6, 31.61 (d, 2J P-C = 6.2 Hz), 31.3 (d, 2J P-C = 6.8 Hz), 30.9, 27.5 (d, 3J P-C = 2.4 Hz), 25.2 (d, 4J P-C = 2.0 Hz); 31 P{1H} NMR (CDCl 3 ): δ 80.64; IR: 2937 (s), 2854 (s), 1623 (w), 1545 (w), 1462 (s), 1374 (s), 1265 (s), 1223 (m), 1145 (m), 1031 (m), 964 (w), 922 (w), 865 (w), 803 (w), 46 751 (w), 720 (w), 637 (s) cm-1. Anal. Calcd for C 24 H 43 F 3 NO 3 PPdS: C, 46.49; H, 7.00; N, 2.26. Found: C, 46.58; H, 7.00; N, 2.27. [(2-Di-tert-butylphosphinocyclobutene-1-(tert-butyl)imine)Pd(allyl)]OTf (10Pd): Sticky brown solid (0.415 g, 71.4%); 1H NMR (CDCl 3 ): δ 7.94 (d, 4J P-H = 1.8 Hz, 1H), 5.60-5.58 (m, 1H), 5.38-5.35 (m, 1H), 4.19-4.16 (m, 1H), 3.99 (d, 3J H-H = 6.6 Hz, 1H), 3.13-3.02 (m, 4H), 2.54 (d, 3J H-H = 12.0 Hz, 1H), 1.42 (d, 3J P-H = 15.0 Hz, 9H), 1.42 (s, 9H), 1.26 (d, 3J P-H = 15.0 Hz, 9H); 13C{1H} NMR (CDCl 3 ): δ 160.3 (d, 1J P-C = 10.7 Hz), 157.5 (d, 3J P-C = 3.9 Hz), 140.5 (d, 2J P-C = 8.6 Hz), 118.5 (d, 2J P-C = 5.3 Hz), 92.3 (d, 2J PC = 25.6 Hz), 65.1, 45.2, 39.9 (d, 1J P-C = 14.6 Hz), 37.6 (d, 1J P-C = 19.2 Hz), 35.3 (d, 3J P-C = 5.3 Hz), 32.1 (d, 2J P-C = 16.6 Hz), 30.6 (d, 2J P-C = 5.7 Hz), 30.5, 30.3 (d, 2J P-C = 4.5 Hz); 31P{1H} NMR (CDCl 3 ): δ 55.18; IR: 2916 (s), 2854 (s), 2719 (m), 2293 (w), 1602 (w), 1457 (s), 1374 (s), 1259 (s), 1151 (m), 1088 (m), 1026 (s), 933 (m), 876 (w), 803 (m), 720 (m), 632 (m) cm-1. Anal. Calcd for C 21 H 37 F 3 NO 3 PPdS: C, 43.64; H, 6.45, N, 2.42. Found: C, 43.00; H, 6.26; N, 2.21. 2.5 Crystallography of 1Pd, 8Pd, and 9Pd A summary of crystal data and collection parameters for crystal structures of 1Pd, 8Pd, and 9Pd are provided in Table 2.3. Detailed descriptions of data collection, as well as data solution, are provided below. ORTEP diagrams were generated with the Diamond 3 software package.96 For each sample, a suitable crystal was mounted on a glass fiber or polymer loop using Paratone-N hydrocarbon oil. The crystal was transferred to a Siemens SMART97 or Apex 2 diffractometer with a CCD area detector, centered in the X-ray 47 beam, and cooled to 140 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω scans, and the data were integrated by the program SAINT.98 The final unit cell parameters were determined by a least-squares refinement of the reflections with I > 2σ(I). Data analysis using Siemens XPREP and the successful solution and refinement of the structure determined the space group.99 Empirical absorption corrections were applied using the program SADABS.100 Equivalent reflections were averaged, and the structures were solved by direct methods using the SHELXTL software package.101 Unless otherwise noted, all non-hydrogen atoms were refined anisotropically. 1Pd: X-ray quality crystals were grown from a pentane layered THF solution at 25 °C. There were two molecules of 1Pd in the asymmetric unit. One triflate anion was disordered over two positions in a nearly 1:1 ratio. The central carbons of both allyl moieties in the asymmetric unit were also disordered over two positions each (3:1 and 3:2 ratios). The final cycle of full-matrix least-squares refinement was based on 11637 observed reflections and 796 variable parameters and converged yielding final residuals: R obs = 0.0432, R all = 0.0595, and GOF = 1.014. 8Pd: X-ray quality crystals were grown from a pentane-layered THF solution at 25 °C. One tert-butyl group was disordered over two positions in a 1:1 ratio. Its carbon atoms were modeled isotropically. The final cycle of full-matrix least-squares refinement was based on 4754 observed reflections and 296 variable parameters and converged yielding final residuals: R obs = 0.0696, R all = 0.0760, and GOF = 1.172. 48 9Pd: X-ray quality crystals were grown from a pentane-layered THF solution at 25 °C. The crystals were twinned about a C 2 rotation axis bisecting a and b (Twin Law: 001 0-10 100). Additionally, one triflate anion was disordered over two positions in a 3:2 ratio. Despite these complications, all non-hydrogen atoms were still refined anisotropically. The final cycle of full-matrix least-squares refinement was based on 12351 observed reflections and 686 variable parameters and converged yielding final residuals: R obs = 0.0484, R all = 0.0574, and GOF = 1.069. 49 Table 2.3 Crystallographic data for compounds 1Pd, 8Pd, and 9Pd. Compound 1Pd 8Pd 9Pd Formula C 30 H 31 F 3 NO 3 PPdS C 23 H 41 F 3 NO 3 PPdS C 24 H 43 F 3 NO 3 PPdS Formula weight 679.99 606.00 620.02 Space group P2 1 /c P-1 P2 1 /n Crystal System Monoclinic Triclinic Monoclinic Temperature (K) 140 140 140 a (Å) 21.331(4) 10.315(2) 22.407(3) b (Å) 9.6895(17) 10.453(2) 11.3067(16) c (Å) 28.509(5) 13.040(3) 22.479(3) α (°) 90.00 73.83(3) 90.00 β (°) 98.402(4) 79.74(3) 91.5780(10) γ (°) 90.00 84.99(3) 90.00 5829.3(17) 1327.8(5) 5692.9(14) 8 2 8 Density calc (g/cm ) 1.550 1.516 1.447 Diffractometer Siemens SMART Bruker APEX2 Bruker APEX2 Radiation Mo-K α (λ = 0.71073 Å) Mo-K α (λ = 0.71073 Å) Mo-K α (λ = 0.71073 Å) Monochromator Graphite Graphite Graphite Detector CCD detector CCD detector CCD detector Scan type, width ω, 0.3° ω, 0.3° ω, 0.3° Scan speed (s) 20 10 10 Reflections measured Hemisphere Hemisphere Hemisphere 2θ range (°) 1.92-56.68 3.30-52.12 3.60-56.06 Crystal dimensions (mm) 0.20 x 0.18 x 0.12 0.40 x 0.05 x 0.04 0.40 x 0.08 x 0.08 Reflections measured 64333 30580 76098 Unique reflections 14493 5201 13680 Observations (I > 2σ(I)) 11637 4754 12351 R int 0.0643 0.0400 0.0516 Parameters 796 296 686 R obs , R w , R all 0.0432, 0.1002, 0.0595 0.0696, 0.1881, 0.0760 GoF 1.014 1.172 3 V (Å ) Z 3 50 0.0484, 0.1296, 0.0574 1.069 Chapter 3 Further Modification of the 3Iminophosphine-Based Palladium Catalyst 3.1 Introduction Expanding upon the results of the second chapter, investigation of the steric and electronic properties of the 3IP ligands and their resulting effect on the catalytic efficiency of their respective palladium complexes continued. This led to the synthetic development and characterization of four new 3IP ligands and [(3IP)Pd(allyl)]OTf complexes. Understanding that changes made to each of the three tunable domains can either promote or destroy hydroamination catalysis with these complexes, further alteration to these three domains proceeded. Two of the new 3IP ligands (11 and 12) contained alterations to the phosphine moiety, while the other two each varied the basicity of the imine moiety (13) and the composition of the unsaturated backbone (14) (Figure 3-1). Ligands 11 and 12 each started with the framework of ligand 4, but exchanged the tertiary carbons of the tert-butyl phosphine groups for the secondary 51 carbons of cyclohexyl groups and primary carbons of iso-butyl groups, respectively. Figure 3-1 3-Iminophosphine (3IP) ligands 11-14. It was previously noted that ligands utilizing alkyl groups instead of aryl groups on the phosphine significantly increased catalytic activity of their palladium complexes,102 so naturally variation of the alkyl group substitution was thought to impact the catalysis. The more basic tert-butyl imine moiety of 2Pd, 4Pd, and 10Pd also led to significantly greater catalytic activity than the less basic 2,6-xylyl imine moieties of 1Pd, 3Pd, 5Pd, and 7Pd, leading to the synthesis of 13, with an even more basic dimethylamino group on the imine. The last ligand in this ancillary array was generated from the notion that decreasing size of the alicyclic backbone led to increased turnover frequency in [(3IP)Pd(allyl)]OTf complexes. Ligand 14 was synthesized without an alicyclic backbone, instead replacing it with a hydrogen atom and tert-butyl group at the 1 and 2 positions, respectively. All ligands in this array were coordinated to Pd(allyl)Cl and the chlorine abstracted with AgOTf to produce their respective [(3IP)Pd(allyl)]OTf complexes, 11Pd-14Pd. The [(3IP)Pd(allyl)]OTf complexes were then screened for their 52 potential to catalyze the hydroamination of 1,1-dimethylallene with substituted anilines in a manner analogous to that of the previous chapter. 3.2 Results and Discussion Ligands 12 and 13 were prepared in a manner analogous to that described by Zingales et al.,102 while 11 and 14 required modified methodologies in order to ensure reaction completion and selectivity for the desired products. Due to its lack of appreciable solubility in diethylether, lithium dicyclohexylphosphide required dissolution in THF in order to be added in a dropwise manner to 2-chlorocyclopentene-1-(tert-butyl)imine. These conditions produced multiple phosphorus containing products, most likely due to the highly reactive nature of this phosphide when compared to lithium di-tertbutylphosphide. A methodology analogous to Kuchenbeiser et al.,71 utilizing a lower reaction temperature (-78 oC), a solvent in which the phosphide was not readily soluble (toluene), a longer reaction time (10 h), and a celite padded frit for extraction, was employed in order to produce the desired product in good yield and purity. Ligand 14, with its lack of alicyclic backbone, was open to two different diastereomers upon attack of the phosphide at the 2 position. Because of this, a methodology analogous to Shaffer et al. was employed in order to select the cis addition product over that of the trans, as the stereochemistry of the trans isomer does not permit chelation to a metal center.47 A dilute solution of chloroimine in pentane was added to a slurry of lithium di-tert-butylphosphide in pentane at -78 oC, allowed to slowly warm to room temperature, then heated at 50 oC for 10 hours to ensure reaction completion. After cooling to room temperature ligand 14 was extracted with pentane using a celite padded 53 frit. Complexes 11Pd and 13Pd required recrystallization of their respective (3IP)Pd(allyl)Cl complexes from pentane in order to achieve successful halide abstraction with AgOTf in the final step. As noted in the previous chapter, silver chloride produced during chloride removal from (3IP)Pd(allyl)Cl complexes was readily coordinated by excess 3IP ligand. This was first observed when an unidentified crystalline material was found to be much less soluble in THF than 4Pd, both of which had been co-crystallized from a pentane layered THF solution. When the low solubility material was observed by 1H NMR spectroscopy, all resonances seemed to indicate uncoordinated ligand, yet the physical appearance of the material seemed to indicate some type of metal complex, as free ligand 4 is a viscous liquid at room temperature. Analysis via 31P NMR spectroscopy displayed neither resonances of 4 nor 4Pd of significant intensity, but instead showed two doublets with the same chemical shift. The compound was further characterized by X-ray crystallography, which revealed the isolated material to be a silver chloride complex (Figure 3-2).103 This was a dimer of AgCl and monodentate 4, coordinated only through the phosphine (4AgCl), which had co-crystallized with 4Pd. To ensure that this complex was not indeed the active hydroamination catalyst, the compound was screened similar to the other species and displayed negligible catalytic activity for the hydroamination of 1,1dimethylallene with 4-fluoroaniline, activity that was consistent with the trace remaining 4Pd in the crystalline mixture. 54 Figure 3-2 ORTEP (50% thermal ellipsoids) of 4AgCl. Hydrogen atoms have been omitted for clarity. Selected bond lengths (in Å): Ag1-P1 = 2.3793(9), Ag1-Cl1 = 2.478(1), Ag1-Cl2 = 2.574(1), Ag1-Ag2 = 3.3422(4), Ag2-P2 = 2.381(1), Ag2-Cl1 = 2.508(1), Ag2-Cl2 = 2.542(1). Bond angles (in deg): Ag1-Ag2-P2 = 175.32(3), Ag2Ag1-P1 = 169.32(3), Cl1-Ag1-Cl2 = 96.70(3), Cl1-Ag2-Cl2 = 96.77(3), Ag1-Cl1-Ag2 = 84.17(3), Ag1-Cl2-Ag2 = 81.58(3), Cl1-Ag1-P1 = 140.30(4), Cl2-Ag2-P2 = 126.38(3). All of the ligands and palladium complexes described in this chapter are diamagnetic, and so an analysis of their NMR spectroscopic features proves quite insightful. Similar to the original array of 10 3IP ligands from Chapter 2, substantial differences were noted between 1 H, 13 C, and 31 P NMR spectra of the free 3- iminophosphine ligands and those of the [(3IP)Pd(allyl)]OTf complexes. These trends are summarized in Table 3.1 below. As was the case with all other 3IP palladium complexes synthesized by our group, downfield shifts in the 31P NMR signals were observed upon coordination of the ligand to the palladium, with a further downfield shift upon chloride abstraction for ligands 11-14. The change in this shift between free ligand and complex (Δ31P δ) is far less varied than the array of ten ligands and complexes found in the 55 previous chapter, since all 3IP ligands in this array have alkyl groups on the phosphine moiety. As larger Δ31P δ seems to denote tighter binding of the phosphine to the metal center, it is implied that 12 and 14, both displaying more than 10 ppm larger difference in their chemical shifts than 11 and 13, are most strongly bound to palladium in this array. Table 3.1 Comparison between selected 31P and 1H NMR resonances of [(3IP)Pd(allyl)]OTf complexes and their respective free 3IP ligands (all values in ppm). 3IPPda 3IPPda 3IPb Δ31P δ 3IPb Δ1H δ 31 31 R'N=CH 1H δ R'N=CH 1H δ Pδ Pδ 30.20 -20.57 50.77 8.05 8.73 -0.68 11 5.60 -56.13 61.73 8.15 8.79 -0.64 12 60.11 12.93 47.18 7.32 7.92 -0.60 13 88.67 23.09 65.58 8.28 8.12 0.16 14 a 3IPPd refers to [(3IP)Pd(allyl)]OTf complex. b 3IP refers to uncoordinated ligand. In fact, 12 and 14 display the greatest Δ31P δ values of all 14 ligands in this thesis, with values of 61.73 and 65.58 ppm, respectively. Both 11 and 12 and their respective palladium complexes displayed 1H NMR resonances for their imine C-H similar to ligands and complexes from the previous chapter, while 13 and 14 showed uncharacteristic variations from the norm. Whereas free ligand imine C-H tends to rest at or around 9 ppm, with an upfield shift (denoting loss of double bond character of the imine moiety upon coordination of the imine nitrogen to palladium) to about 8 ppm for the respective 3IP palladium complexes, 13 starts with a resonance of 7.92 ppm that shifts upfield to 7.32 ppm for 13Pd. The change in imine C-H resonance upon coordination (Δ1H δ) is still comparable to those of the other alkyl phosphino-complexes, -0.60 ppm (the negative number denoting an upfield shift from ligand to triflated complex). Ligand 14, however, displayed a reversed value for Δ1H δ, with a 0.16 ppm downfield shift between free ligand and [(3IP)Pd(allyl)]OTf complex. This may imply 56 that the conjugated pi system of the non-cyclic alkene is permitting the electronegative phosphorus atom to draw electron density away from the imine carbon and hydrogen. This is most likely a result of significant electron donation from the phosphorus atom to the metal center. Similar to the complexes of the previous chapter, the trends in the 13 C NMR spectra parallel those of the 1H NMR spectra, as there are significant changes in the chemical shift of the imine carbon between free and coordinated ligands. The terminal carbons of the allyl ligands (cis and trans to phosphorus) were readily differentiated based upon both the magnitude of the J P-C coupling constant, and their relative chemical shift values. The trans carbon was typically located downfield from the cis carbon and displayed a J P-C coupling constant an order of magnitude larger, if the cis carbon displayed coupling to phosphorus at all. Results for the catalytic screening of compounds 11Pd-14Pd, along with compounds 2Pd, 4Pd, and 10Pd for comparison, are summarized in Table 3.2 below. All four complexes displayed greatly decreased catalytic activity in the hydroamination of 1,1-dimethylallene with substituted anilines when compared to the most active complexes from the previous array. Changing from the tertiary carbons of the phosphine moiety of 4Pd to the secondary carbons of 11Pd and the primary carbons of 12Pd showed a marked drop in activity for each successive decrease in substitution. The phenyl groups of 2Pd seem to afford it intermediate catalytic activity when compared to 4Pd and 12Pd. The cone angle of these phosphines decreases going from tert-butyl to cyclohexyl to phenyl to iso-butyl groups,104 indicating that steric bulk of the phosphine substituents may play an important role in hydroamination catalysis. 57 Table 3.2 Conversion to product A for the [(3IP)Pd(allyl)]OTf catalyzed hydroamination of 1,1-dimethylallene with aryl amines (complexes 11Pd-14Pd). Conversion was monitored via 1H NMR spectroscopy. Aniline 2Pd 4Pd 10Pd 11Pd 12Pd 13Pd 14Pd -- 60% 91% 7% -- 18% 16% -- -- NP NP 12% -- NP NP 9% -- NP NP 8% -- NP 7% 6% -- 14% NP 9% -- NP NP 2-Methyl ---Aniline 3-Methyl 13% >95% 92% Aniline 4-Methyl 16% >95% >95% Aniline 4-tertButyl 17% 88% >95% Aniline 4-Fluoro 9% 65%* 90% Aniline 3-Methoxy 12% 62% 72% Aniline * indicates reaction at 70oC. “--” indicates performed. <5%. NP indicates a trial that was not Substitution of the more basic dimethylamino imine for the tert-butyl imine of 4Pd to make 13Pd did not increase its hydroamination catalytic activity. This may be attributed to tighter binding of its imine nitrogen donor atom. Stronger coordination of the nitrogen decreases the hemilability of this ligand more than the other complexes, restricting coordination of the substrate amine during the proposed catalytic cycle (Scheme 1.4). Removal of the alicyclic backbone of 4Pd to make 14Pd also did not increase catalytic activity. The extremely electron donating nature of its phosphine moiety compared to the other palladium complexes in this thesis (based upon its greater 58 Δ31P δ value) may create a much less Lewis acidic metal center that is less likely to be coordinated by substrates for hydroamination. Also, the lack of a cyclic backbone eliminates the angular strain of this ligand domain, a strain that is maximized in the most active catalyst thus far, 10Pd. 3.3 Conclusions Continued efforts to improve the performance of 3-iminophosphine-based palladium catalysts for the hydroamination of 1,1-dimethylallene with substituted anilines have concluded that the ligand composed of di-tert-butyl phosphine, cyclobutene backbone, and tert-butyl imine still provides the most active palladium catalyst for this hydroamination when compared to the other complexes in this collection. Tertiary aliphatic groups on the phosphine are necessary for effective catalysis, as primary and secondary aliphatics and aromatic groups decrease the catalytic activity. Imine moieties of both low and high basicity were also shown to hinder catalysis, indicating that intermediate basicity is ideal in this system. Increased ring strain in the alicyclic backbone was found to have beneficial effects for hydroamination catalysis, whereas removal of this domain was shown to slow catalysis in all cases. 3.4 Experimental Section 3.4.1 General Methods and Instrumentation: Alicyclic α,β-unsaturated β-chloroaldehydes and β-chloroimines were handled under ambient atmospheric conditions. All other manipulations were performed under an inert N 2 atmosphere using standard Schlenk and drybox techniques. Solvents were dried 59 prior to use; methylene chloride was passed through two columns of 4 Å molecular sieves and degassed with nitrogen. Pentane, diethyl ether, and toluene were passed through columns of activated alumina and 4 Å molecular sieves and degassed with nitrogen. Tetrahydrofuran was distilled from sodium metal and degassed with nitrogen. nButyllithium (1.6 M in hexanes), (allyl)palladium(II) chloride dimer, di-isobutylphosphine, di-tert-butylchlorophosphine, lithium aluminum hydride, and silver triflate were purchased from Strem and used without further purification. Dicyclohexylphosphine was purchased commercially and used without further purification. Phosphorus oxychloride, tert-butylamine, pinacolone, and cyclopentanone were purchased from Acros and used without further purification. 1,1-Dimethylallene was purchased from Alfa Aesar and used without further purification. Dimethylformamide was purchased from BDH and stored over 4 Å molecular sieves. N,N-Dimethylhydrazine was purchased from Sigma-Aldrich and used without further purification. Anilines were also purchased from Sigma-Aldrich or another commercial source and dried over calcium hydride, either neat (liquid anilines) or as solutions in methylene chloride (solid anilines). Liquid anilines were freeze-pump-thawed three times and vacuum distilled. Solutions of solid anilines in methylene chloride were freezepump-thawed three times, filtered, and the methylene chloride removed via reduced pressure. CDCl 3 was purchased from Cambridge Isotope Laboratories, vacuum transferred from CaH 2 , and stored over 4 Å molecular sieves. Benzene-d 6 was also purchased from Cambridge Isotope Laboratories, vacuum transferred from sodium metal, and stored over 4 Å molecular sieves. Silica gel (Porosity: 60 Å, Particle size: 40-63 μm) was purchased from Sorbent Technologies and used as received. 1H and 60 13 C NMR data were obtained on a 600 MHz Inova or 400 MHz VXRS NMR spectrometer at ambient temperature at 599.9 MHz for 1H NMR and 150.8 MHz for 13C NMR and 399.95 MHz for 1H NMR and 100.56 MHz for 13 C NMR, respectively. All 31 P NMR spectra were collected on a 400 MHz VXRS NMR spectrometer at ambient temperature at 161.90 MHz. All spectra were taken using C 6 D 6 or CDCl 3 as the NMR solvent. 1H NMR shifts are given relative to the residual solvent resonances at 7.16 and 7.26 ppm, respectively, and 13C NMR shifts are given relative to the residual solvent peak of CDCl 3 (77.36 ppm). 31 P NMR spectra were externally referenced to 0.00 ppm with 5% H 3 PO 4 in D 2 O. IR samples were prepared as Nujol mulls and taken between KBr plates on a Perkin-Elmer XTL FTIR spectrophotometer. Melting points were observed on a capillary melting point (Uni-Melt) apparatus in sealed capillary tubes and are uncorrected. X-ray structure determinations were performed at the Ohio Crystallographic Consortium, housed at The University of Toledo. Elemental analyses were determined by Atlantic Microlab, Inc., Norcross, GA or Galbraith Laboratories, Inc., Knoxville, TN. High resolution mass spectrometry using electrospray ionization was performed at the University of Illinois Mass Spectrometry Laboratory, Urbana, IL. 3.4.2 General Procedure for the Catalytic Hydroamination Screening of Compounds 11Pd-14Pd All manipulations were performed under an N 2 atmosphere. 3-Methyl-1,2-butadiene (68 mg, 1 mmol) was added to a mixture of amine (0.5 mmol), [(3IP)Pd(allyl)]OTf complex (5 mol%), and deuterated benzene (0.8 ml). Conversion to products was monitored via 1H NMR spectroscopy. Hydroamination products formed were reported previously.3 61 3.4.3 Synthesis and Characterization of Reaction Products The following compounds were synthesized as previously reported: LiPtBu 2 ,3 2chlorocyclopentenecarboxaldehyde,88 2-chlorocyclopentene-1-(tert-butyl)imine,88 Z-3chloro-3-tert-butylpropenal,105 and E-2-chloro-2-tert-butylethene-1-(tert-butyl)imine.105 LiPiBu 2 and LiPCy 2 were both synthesized using methodologies analogous to Shaffer et al.88 2-Chlorocyclopentene-1-(dimethylamino)imine: golden yellow liquid (2.817 g, 62.46%); 1H NMR (CDCl 3 ): δ 7.17 (s, 1H), 2.90 (s, 6H), 2.67-2.64 (m, 2H), 2.63-2.60 (m, 2H), 1.97-1.92 (m, 2H); 13 C{1H} NMR (CDCl 3 ): δ 134.8, 128.7, 128.6, 43.0, 39.0, 31.1, 21.3; IR: 2956 (s), 2857 (s), 2790 (s), 2592 (w), 2493 (w), 2393 (w), 2305 (w), 2106 (w), 1893 (w), 1761 (w), 1628 (m), 1551 (s), 1469 (s), 1441 (s), 1402 (m), 1364 (m), 1325 (s), 1270 (s), 1198 (w), 1132 (s), 1104 (s), 1044 (s), 944 (s), 911 (m), 878 (m), 851 (m), 801 (m), 751 (m), 553 (s) cm-1. 2-Dicyclohexylphosphinocyclopentene-1-(tert-butyl)imine (11): To a Schlenk tube was added lithium dicyclohexylphosphide (1.6 equiv.), a stirbar, and toluene (30 ml). This rapidly stirring slurry was cooled to -78 oC via a dry ice/isopropanol bath for 10 min before slowly adding a solution of degassed 2-chlorocyclopentene-1(tert-butyl)imine (1.00 equiv.) in toluene (30 ml), also cooled to -78 oC for 10 min. The reaction mixture was allowed to slowly warm to room temperature and react for 10 additional hours before solvent was removed in vacuo. The resulting oil was triturated 62 with pentane (2 X 10 ml), then extracted into pentane (2 X 20 ml) and passed through a celite padded frit. Solvent was again removed in vacuo to yield the final product. thick orange oil (0.615 g, 68.3%); 1H NMR (CDCl 3 ): δ 8.73 (d, 4J P-H = 4.8 Hz, 1H), 2.722.69 (m, 2H), 2.63-2.61 (m, 2H), 1.86-1.58 (m, 14H), 1.30-1.07 (m, 10H), 1.21 (s, 9H); 13 C{1H} NMR (CDCl 3 ): δ 155.3 (d, 2J P-C = 17.9 Hz), 154.2 (d, 3J P-C = 23.7 Hz), 147.2 (d, 1J P-C = 26.8 Hz), 57.6, 37.8 (d, 2J P-C = 6.0 Hz), 33.9 (d, 3J P-C = 5.3 Hz), 33.1 (d, 2J P-C = 9.5 Hz), 30.9 (d, 1J P-C = 16.3 Hz), 30.7 (d, 2J P-C = 8.1 Hz), 30.3, 27.53 (d, 3J P-C = 0.9 Hz), 27.46 (d, 4J P-C = 3.3 Hz), 26.8 (d, 3J P-C = 0.9 Hz), 23.3 (d, 3J P-C = 0.9 Hz); 31P{1H} NMR (CDCl 3 ): δ – 20.57; IR: 2926 (s), 2854 (s), 2657 (w), 2262 (w), 1623 (s), 1571 (m), 1446 (s), 1363 (s), 1265 (s), 1213 (s), 1176 (s), 1073 (m), 995 (s), 964 (m), 886 (m), 844 (s), 803 (m), 746 (w), 709 (w) cm-1. HRMS (m/z): [M+H]+ calcd for C 22 H 39 NP 348.2820, found 348.2828. [(2-Dicyclohexylphosphinocyclopentene-1-(tert-butyl)imine)Pd(allyl)]OTf (11Pd): Required recrystallization of (2-dicyclohexylphosphinocyclopentene-1-(tert- butyl)imine)Pd(allyl)Cl intermediate from pentane before preparation in a manner analogous to Zingales et al.102 Orange yellow solid (0.155 g, 53.2%); 1H NMR (CDCl 3 ): δ 8.05 (d, 4J P-H = 1.8 Hz, 1H), 5.64-5.57 (m, 1H), 5.15-5.12 (m, 1H), 3.99-3.95 (m, 1H), 3.73 (d, 3J H-H = 7.2 Hz, 1H), 2.92-2.89 (m, 2H), 2.86-2.82 (m, 1H), 2.73-2.70 (m, 1H), 2.49 (d, 3J H-H = 12.0 Hz, 1H), 2.26-2.21 (m, 1H), 2.10-2.01 (m, 3H), 1.88-1.72 (m, 10H), 1.44 (s, 9H), 1.40-1.06 (m, 10H); 13 C{1H} NMR (CDCl 3 ): δ 160.5 (d, 3J P-C = 7.2 Hz), 156.2 (d, 2J P-C = 13.9 Hz), 133.4 (d, 1J P-C = 24.4 Hz), 119.7 (d, 2J P-C = 5.6 Hz), 88.5 (d, 2J P-C = 27.2 Hz), 65.5, 46.4, 63 38.5 (d, 2J P-C = 11.0 Hz), 37.5, 36.1 (d, 1J P-C = 22.9 Hz), 35.3 (d, 1J P-C = 26.1 Hz), 30.5 (d, 2J P-C = 3.9 Hz), 30.3, 29.2, 29.1, 27.2, 27.1 (d, 2J P-C = 3.6 Hz), 27.0 (d, 2J P-C = 5.3 Hz), 26.9 (d, 2J P-C = 2.0 Hz), 26.8, 26.3 (d, 3J P-C = 1.1 Hz), 26.1 (d, 3J P-C = 1.1 Hz), 23.0 (d, 3J P-C = 4.2 Hz); 31 P{1H} NMR (CDCl 3 ): δ 30.20; IR: 2920 (s), 2854 (s), 1460 (s), 1376 (m), 1263 (m), 1146 (w), 1090 (w), 1027 (m), 797 (w), 722 (w), 634 (m) cm-1. Anal. Calcd for C 26 H 43 F 3 NO 3 PPdS: C, 48.49; H, 6.73; N, 2.17. Found: C, 46.51; H, 6.77; N, 1.90. 2-Di-iso-butyl-phosphinocyclopentene-1-(tert-butyl)imine (12): Prepared in a manner analogous to that of Zingales et al.102 Red-orange oil (0.718 g, 97.1%); 1H NMR (CDCl 3 ): δ 8.79 (d, 4J P-H = 4.8 Hz, 1H), 2.702.68 (m, 2H), 2.58-2.56 (m, 2H), 1.85-1.82 (m, 2H), 1.60-1.56 (m, 2H), 1.54-1.50 (m, 2H), 1.28-1.24 (m, 2H), 1.21 (s, 9H), 0.96 (d, 3J H-H = 6.6 Hz, 6H), 0.93 (d, 3J H-H = 6.6 Hz, 6H); 13C{1H} NMR (CDCl 3 ): δ 153.54 (d, 2J P-C = 19.2 Hz), 153.53 (d, 3J P-C = 24.4 Hz), 149.7 (d, 1J P-C = 25.0 Hz), 57.6, 36.9 (d, 1J P-C = 9.8 Hz), 34.2 (d, 3J P-C = 5.0 Hz), 34.0 (d, 2J P-C = 6.5 Hz), 30.3, 26.8 (d, 2J P-C = 12.8 Hz), 24.9 (d, 3J P-C = 8.3 Hz), 24.0 (d, 3 J P-C = 10.0 Hz), 22.8 (d, 3J P-C = 1.1 Hz); 31 P{1H} NMR (CDCl 3 ): δ -56.13; IR: 3186 (m), 2958 (s), 2885 (s), 2719 (m), 2657 (w), 2615 (m), 1654 (m), 1623 (s), 1581 (m), 1462 (s), 1415 (m), 1384 (s), 1363 (s), 1332 (m), 1259 (s), 1213 (s), 1166 (s), 1104 (s), 1078 (s), 1042 (s), 964 (m), 922 (m), 896 (m), 834 (m), 803 (s), 735 (m), 704 (m) cm-1. HRMS (m/z): [M+H]+ calcd for C 18 H 35 NP 296.2507, found 296.2506. 64 [(2-Di-iso-butyl-phosphinocyclopentene-1-(tert-butyl)imine)Pd(allyl)]OTf (12Pd): Prepared in a manner analogous to that of Zingales et al.102 Tan brown solid (1.208 g, 93.09%); 1H NMR (CDCl 3 ): δ 8.15 (s, 1H), 5.74-5.67 (m, 1H), 5.12-5.10 (m, 1H), 4.09-4.04 (m, 1H), 3.51 (d, 3J H-H = 3.6 Hz, 1H), 2.96-2.93 (m, 2H), 2.79-2.74 (m, 2H), 2.49 (d, 3J H-H = 11.4 Hz, 1H), 2.21-2.16 (m, 1H), 2.11-2.07 (m, 3H), 1.94-1.90 (m, 1H), 1.86-1.84 (m, 1H), 1.73-1.70 (m, 1H), 1.51-1.50 (m, 1H), 1.48 (s, 9H), 1.08 (d, 3J H-H = 6.6 Hz, 3H), 0.98 (d, 3J H-H = 6.6 Hz, 3H), 0.96 (d, 3J H-H = 6.6 Hz, 3H), 0.89 (d, 3J H-H = 6.6 Hz, 3H); 13C{1H} NMR (CDCl 3 ): δ 158.2 (d, 3J P-C = 8.4 Hz), 153.2 (d, 2J P-C = 16.0 Hz), 135.6 (d, 1J P-C = 28.1 Hz), 119.9 (d, 2J P-C = 6.3 Hz), 90.8 (d, 2 J P-C = 28.2 Hz), 66.2, 48.5, 39.6 (d, 2J P-C = 11.5 Hz), 37.5 (d, 1J P-C = 28.7 Hz), 36.3 (d, 1 J P-C = 30.0 Hz), 34.2, 30.4, 26.9, 26.6, 25.0 (d, 3J P-C = 10.3 Hz), 24.4 (d, 3J P-C = 5.0 Hz), 24.3 (d, 3J P-C = 4.0 Hz), 24.2 (d, 3J P-C = 9.5 Hz), 22.6 (d, 3J P-C = 5.1 Hz); 31P{1H} NMR (CDCl 3 ): δ 5.60; IR: 2916 (s), 2854 (s), 2719 (m), 2677 (w), 1591 (w), 1462 (s), 1379 (m), 1265 (m), 1223 (m), 1140 (m), 1099 (w), 1062 (w), 1031 (m), 948 (w), 844 (w), 808 (w), 751 (w), 720 (w), 637 (m) cm-1. Anal. Calcd for C 22 H 39 F 3 NO 3 PPdS: C, 44.64; H, 6.64; N, 2.37. Found: C, 44.78; H, 6.73; N, 2.39. 2-Di-tert-butylphosphinocyclopentene-1-(dimethylamino)imine (13): Prepared in a manner analogous to that of Zingales et al.102 orange brown oil (0.320 g, 39.1%); 1H NMR (CDCl 3 ): δ 7.92 (d, 4J P-H = 5.4 Hz, 1H), 2.88 (s, 6H), 2.80-2.77 (m, 2H), 2.65-2.62 (m, 2H), 1.84-1.79 (m, 2H), 1.17 (d, 3J P-H = 12.0 Hz, 18H); 13 C{1H} NMR (CDCl 3 ): δ 154.8 (d, 2J P-C = 22.8 Hz), 137.2 (d, 1J P-C = 65 29.6 Hz), 133.9 (d, 3J P-C = 28.8 Hz), 43.3, 39.3 (d, 3J P-C = 6.5 Hz), 33.4 (d, 2J P-C = 6.6 Hz), 33.0 (d, 1J P-C = 19.3 Hz), 31.1 (d, 2J P-C = 14.3 Hz), 24.2; 31P{1H} NMR (CDCl 3 ): δ 12.93; IR: 2947 (s), 2885 (s), 2854 (s), 2781 (m), 2708 (w), 1628 (w), 1571 (s), 1550 (m), 1534 (m), 1467 (s), 1420 (m), 1384 (m), 1363 (s), 1322 (m), 1265 (s), 1171 (m), 1135 (s), 1104 (s), 1078 (s), 1036 (s), 943 (m), 896 (m), 852 (m), 807 (s), 746 (m), 601 (m), 551 (s) cm-1. [(2-Di-tert-butylphosphinocyclopentene-1-(dimethylamino)imine)Pd(allyl)]OTf (13Pd): Required recrystallization of (2-di-tert-butylphosphinocyclopentene-1- (dimethylamino)imine)Pd(allyl)Cl intermediate from pentane before preparation in a manner analogous to that of Zingales et al.102 sticky yellow solid (0.050g, 63%); 1H NMR (CDCl 3 ): δ 7.32 (s, 1H), 5.86-5.81 (m, 1H), 5.02-4.99 (m, 1H), 4.20-4.16 (m, 1H), 3.90 (d, 3J H-H = 6.0 Hz, 1H), 2.98 (s, 6H), 2.862.77 (m, 4H), 2.74 (d, 3J H-H = 12.0 Hz, 1H), 2.00-1.96 (m, 2H), 1.38 (d, 3J P-H = 15.0 Hz, 9H), 1.25 (d, 3J P-H = 14.4 Hz, 9H); 13C{1H} NMR (CDCl 3 ): δ 153.4 (d, 2J P-C = 13.1 Hz), 141.1 (d, 3J P-C = 2.6 Hz), 128.8 (d, 1J P-C = 19.8 Hz), 120.4 (d, 2J P-C = 4.7 Hz), 91.7 (d, 2 J P-C = 23.5 Hz), 49.9, 45.5, 39.3 (d, 1J P-C = 16.0 Hz), 39.2 (d, 2J P-C = 11.0 Hz), 37.9 (d, 1 J P-C = 17.0 Hz), 30.9 (d, 2J P-C = 6.2 Hz), 30.7 (d, 2J P-C = 5.7 Hz), 30.0 (d, 3J P-C = 5.4 Hz), 23.9 (d, 3J P-C = 3.6 Hz); 31P{1H} NMR (CDCl 3 ): δ 60.11. 66 Z-2-Di-tert-butylphosphino-2-tert-butylethene-1-(tert-butyl)imine (14): To a Schlenk tube was added lithium di-tert-butylphosphide (1.6 equiv.), a stirbar, and pentane (50 ml). This rapidly stirring slurry was cooled to -78 o C via a dry ice/isopropanol bath for 10 min before slowly adding a solution of degassed E-2-chloro2-tert-butylethene-1-(tert-butyl)imine (1.00 equiv.) in pentane (30 ml), also cooled to -78 o C. The reaction mixture was allowed to slowly warm to room temperature before heating at 50 oC for 10 h. The crude product mixture was allowed to cool to room temperature before passage through a celite padded frit. Solvent was removed in vacuo to yield the final product. orange brown oil (0.517 g, 63.2%); 1H NMR (CDCl 3 ): δ 8.12 (d, 3J H-H = 9.2 Hz, 1H), 6.99 (m, 1H), 1.26 (d, 3J P-H = 9.6 Hz, 18H), 1.25-1.21 (br, s, 18H); 13 C{1H} NMR (CDCl 3 ): δ 160.2, 158.9 (d, 1J P-C = 51.9 Hz), 138.7 (d, 2J P-C = 7.8 Hz), 58.1, 40.7 (d, 1J PC = 34.4 Hz), 33.7 (d, 2J P-C = 30.8 Hz), 32.8 (d, 2J P-C = 16.2 Hz), 31.9 (d, 3J P-C = 10.8 Hz), 30.4; 31P{1H} NMR (CDCl 3 ): δ 23.09. [(Z-2-Di-tert-butylphosphino-2-tert-butylethene-1-(tert-butyl)imine)Pd(allyl)]OTf (14Pd): Prepared in a manner analogous to that of Zingales et al.102 Light brown solid (0.285g, 58.33%); 1H NMR (CDCl 3 ): δ 8.28-8.27 (m, 1H), 7.32 (dd, 3 J P-H = 39.0 Hz, 3J H-H = 6.0 Hz, 1H), 5.64-5.57 (m, 1H), 4.84-4.83 (m, 1H), 3.92 (d, 3J H-H = 6.0 Hz, 1H), 3.61-3.57 (m, 1H), 2.94 (d, 3J H-H = 12.6 Hz, 1H), 1.55 (d, 3J P-H = 15.0 Hz, 67 9H), 1.47 (d, 3J P-H = 15.0 Hz, 9H), 1.45 (s, 9H), 1.39 (s, 9H); 31P{1H} NMR (CDCl 3 ): δ 88.67. (2-Di-tert-butylphosphinocyclopentene-1-(tert-butyl)imine) 2 Ag 2 Cl 2 (4AgCl): Produced as a byproduct during chloride removal from the (2-di-tert- butylphosphinocyclopentene-1-(tert-butyl)imine)Pd(allyl)Cl intermediate via addition of AgOTf when excess 4 was allowed to remain dissolved in the reaction mixture. Work-up of both complexes simultaneously is achieved via a methodology analogous to that of Zingales et al.102 Co-crystallization of 4Pd and 4AgCl from a pentane layered THF solution affords an otherwise pure mixture of both complexes. 4Pd is then readily rinsed away from 4AgCl with THF (2 × 10 ml). brown crystalline solid; 1H NMR (CDCl 3 ): δ 9.19 (s, 2H), 2.95-2.92 (m, 4H), 2.81-2.78 (m, 4H), 1.91-1.89 (m, 4H), 1.36 (d, 3J P-H = 15.0 Hz, 36H), 1.28 (s, 18H); 13C{1H} NMR (CDCl 3 ): δ 158.9 (d, 2J P-C = 9.7 Hz), 151.4 (d, 3J P-C = 17.6 Hz), 135.0 (d, 1J P-C = 14.3 Hz), 59.1, 40.4 (d, 3J P-C = 2.4 Hz), 35.9 (d, 1J P-C = 13.9 Hz), 35.2 (d, 2J P-C = 9.5 Hz), 31.0 (d, 2J P-C = 9.2 Hz), 30.3, 23.5 (d, 3J P-C = 4.2 Hz); 1 31 P{1H} NMR (CDCl 3 ): δ 36.16 (d, J 107Ag-P = 600.8 Hz), 36.16 (d, 1J 109Ag-P = 689.8 Hz). 3.5 Crystallography of 4AgCl A summary of crystal data and collection parameters for the crystal structure of 4AgCl is provided in Table 3.3. A detailed description of data collection, as well as the data solution, is provided below. The ORTEP diagram was generated with the Diamond 3 software package.96 A suitable crystal was mounted on a polymer loop using Paratone-N hydrocarbon oil. The crystal was transferred to an Apex 2 diffractometer with a CCD 68 area detector, centered in the X-ray beam, and cooled to 140 K using a nitrogen-flow low-temperature apparatus that had been previously calibrated by a thermocouple placed at the same position as the crystal. An arbitrary hemisphere of data was collected using 0.3° ω scans, and the data were integrated by the program SAINT.98 The final unit cell parameters were determined by a least-squares refinement of the reflections with I > 2σ(I). Data analysis using Siemens XPREP99 and the successful solution and refinement of the structure determined the space group. Empirical absorption corrections were applied using the program SADABS.100 Equivalent reflections were averaged, and the structure was solved by direct methods using the SHELXTL software package.101 All non-hydrogen atoms were refined anisotropically. 4AgCl: X-ray quality crystals were grown from a pentane layered THF solution at -25 °C. The final cycle of full-matrix least-squares refinement was based on 5605 observed reflections and 397 variable parameters and converged yielding final residuals: R obs = 0.0266, R all = 0.0291, and GOF = 1.113. 69 Table 3.3 Crystallographic data for compound 4AgCl. Compound 4AgCl Formula C 36 H 68 Ag 2 Cl 2 N 2 P 2 Formula weight 877.50 Space group P2 1 /n Crystal System Monoclinic Temperature (K) 140 a (Å) 16.0222(5) b (Å) 13.0015(4) c (Å) 20.2613(6) α (°) 90.00 β (°) 101.220(1) γ (°) 90.00 3 V (Å ) 4140.0(2) Z 4 3 Density calc (g/cm ) 1.408 Diffractometer Bruker APEX2 Radiation Cu-K α (λ = 1.54178 Å) Monochromator Graphite Detector CCD detector Scan type, width ω, 0.3° Scan speed (s) 10 Reflections measured Hemisphere 2θ range (°) 7.82-117.86 Crystal dimensions (mm) 0.10 x 0.01 x 0.01 Reflections measured 24029 Unique reflections 5804 Observations (I > 2σ(I)) 5605 R int 0.0297 Parameters 397 R obs , R w , R all 0.0266, 0.0740, 0.0291 GoF 1.113 70 References (1) Trost, B. M. Atom economy-a challenge for organic synthesis: Homogeneous catalysis leads the way. Angewandte Chemie-International Edition in English 1995, 34, 259-281. (2) Mueller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. 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