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Recent Advances of
Alkyne Metathesis
Group Meeting
Timothy Chang
11-09-10
Fischer Carbyne and Schrock Alkylidyne
Fischer
Schrock
Doublet
Quartet
LX type
X3 type
4e
6e
-1
-3
lone pair
covalent
p-back bonding
3 covalents
Weak donor L
Strong donor L
The Organometallic Chemistry of the Transition Metals, 4th Ed., Crabtree.
Organotransition Metal Chemistry, From Bonding to Catalysis, Hartwig.
Group Orbitals of +CR Fragment
Carbyne Complexes, Fischer et. al.
1988, VCH
MOs of Fischer Carbyne
Carbyne Complexes, Fischer et. al. 1988, VCH
Group Orbitals of L3M- Fragment
Encyclopedia of Inorganic Chemistry,
Electronic Structure of Organometallic Compounds,
Albright, T. A.
Molecular Orbitals of L3M(CR)
Carbyne Complexes, Fischer et. al. 1988, VCH
A Brief History of Alkyne Metathesis
Pennellar, F.; Banks, R. L.; Bailey, G. C. J. Chem. Soc., Chem. Commun. 1968, 1548.
Mortreux, A.; Blanchard, M. J. Chem. Soc., Chem. Commun. 1974, 786.
Katz, T. J.; McGinnis, J. J. Am. Chem. Soc. 1975, 97, 1592.
For an account, see Schrock, R. R. Polyhedron, 1995, 14, 3177.
Catalyst Deactivation by Dimerization and Ring Expansion
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
“Pseudopoisoning” Effect
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
Preparation of (Me3CO)3W(CCMe3)
Schrock et. al. J. Am. Chem. Soc. 1981, 103, 3932.
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
Application to RCAM
Thioether, basic nitrogen containing functional groups are not compatible.
Tolerate acidic proton of a secondary amide.
Fürstner et. al. Angew. Chem. Int. Ed. 1998, 37, 1734 and J. Am. Chem. Soc. 1999, 121, 11108.
Curious Effect of Halogenated Solvents
Secondary amide is
not tolerated.
Fürstner et. al. Chem. Eur. J. 2001, 7, 5299 and J. Am. Chem. Soc. 1999, 121, 9453
Major Components of the Molybdenum Species
Ar = 3,5-xylyl
Why is 3 not catalytically active?
Why are terminal alkynes not viable substrates?
“Deprotiometallacyclobutadiene”
Schrock et. al. J. Am. Chem. Soc. 1985, 107, 5987
Polyhedron 1995, 15, 3177
1:2
not active
Cross Metathesis
1
Fürstner , A., Mathes, C. Org. Lett. 2001, 3, 221
Cross Metathesis
1
Fürstner , A., Mathes, C. Org. Lett. 2001, 3, 221
Application of RCM and RCAM to Macrocyclization
RCM
Schinzer et. al. ACIEE 1997, 36, 523.
RCAM
Fürstner et. al. Chem. Eur. J. 2003, 7, 5299.
Reductive Recycle Strategy for Catalyst Preparation
Ar = 3,5-xylyl
- Active catalyst is generated in the presence of various phenols.
- Electron-deficient ligands make the catalysts more active e.g. p-nitrophenol (low cost)
- Catalyst is active in MeCN even though it is a coordinating solvent.
- Secondary amide and thiophene containing molecules can be used.
- Bulky ligand is not required. Apparently electronic factor dominates.
- Bulky ligands slows down both dimerization and metathesis presumably.
Moore et. al. Org. Syn. 2007, 84, 163.
Effects of Alkyl Substituent and Ligand
R = Et
5
Ar = 3,5-xylyl
Optimal R = Et
Optimal Ligand
= p-nitrophenol
(cheaper)
R = Me gives polybutyne
Equilibrium ratio of 13:14 = 2:3 (established from both 13 and 14, respectively)
Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.
Homodimerization Substrate Scope
R = Et
5
Ar = 3,5-xylyl
a Closed system, d8-toluene, 20 °C, t1/2 is the time required for the reaction to reach 50% of final constant ratio of 10 to 12.
b Open driven condition, solvent 1,2,4-trichlorobenzene, 30 °C, 22 h, 1 mm Hg, yield based on isolated product. c Ligand A )
R,R,R-trifluoro-o-cresol. d Ligand B ) p-nitrophenol.
Solvent Effect and Precipitation Strategy
R = Et
5
Ar = 3,5-xylyl
Conversion
CHCl3, Toluene: 100% (0.5 h)
CH3CN, THF: 76% (8 h)
Acetone: 40% (catalyst decomposition)
DMF, MeOH: 0%
Precipitation strategy can be utilized to drive the equilibrium towards desired
product such as 7.
Aprotic, non-coordinating solvents are preferred.
Moore et. al. J. Am. Chem. Soc. 2004, 126, 329.
Preparation of Shape-Persistent Macrocycles by PPT Strategy
Zhang, W.; Moore, J. S.
J. Am. Chem. Soc. 2004, 126, 12796.
Catalyst Prepared from Nitrides by Metathesis with Alkynes
One major reason that
MeCN cannot be used
Schrock, Organometallics 1986, 5, 398.
Johnson et. al. J. Am. Chem. Soc. 2006, 128, 9614.
Johnson et. al. Inorg. Chem. 2005, 44, 9140.
- 36 and 38 are preferred thermodynamically.
- The formation of 38 is irreversible.
- Idea: in situ generation of catalyst by metal nitride/metal alkylidyne interconversion
Zhang, W.; Moore, J. S. Adv. Synth. Catal. 2007, 349, 93.
Development Towards a Robust and Practical Precatalyst
distorted square pyramidal
Fürstner et. al. J. Am. Chem. Soc. 2009, 131, 9468.
Scope
11 can be weighed in air
and used under dry air
(need increased loading)
Incompatible: epoxide,
aldehyde, acyl chloride
Fürstner et. al.
J. Am. Chem. Soc.
2009, 131, 9468
Improvements on Triphenylsilanolate Bound Mo (Pre)Catalyst
Typical Reaction Conditions for Homodimerization, CM, RCAM
(A) 15 (10 mol %), MnCl2 (10 mol %), MS 5 Å, toluene, 80 °C, 30 min, then
addition of the substrate and reaction at 80 °C or 100 °C (for CM).
(B) 24 (2 mol %), toluene, ambient temperature, MS 5 Å.
(C) 25 (5 mol %), MnCl2 (5 mol %), toluene, 80 °C, 30 min; then addition of
the substrate and MS 5 Å, and reaction at ambient temperature.
15 is stable on bench top for storage.
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Scope
Incompatible with aldehyde.
Previous stoichiometric
experiment showed its
conversion to nitrile.
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Roles of Molecular Sieve
MS removes butyne
MS helps liberate Et2O
3 Å MS has no sig. effect (i.e. not equilibrium effect of H2O)
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Probing the Active Mo Species
trace
Hypotheses:
“The small amounts of alkylidynes, such as 16, formed in the mixture must be superbly active”
“12.L acts as a reservoir (slow release) (still show catalytic activity at 80 oC for days)
The hypotheses were tested using 19 and 24.
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Preparation of Molybdenum Alkylidyne Complexes
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
An Extraordinary Active Metathesis Catalyst
Equilibrium reached at ~ 25 min
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 11045.
Application of RCAM to the Synthesis of Lactimidomycin
Lactimidomycin
Seven sp2 C in a
12-membered lactone
Key steps: Ring closing alkyne metathesis and trans-hydrosilylation
1.2 g scale
84%
Fürstner et. al. J. Am. Chem. Soc. 2010, 132, 14064.
Imidazolin-2-iminato Tungsten Catalyst
hexane
(4.5 mM)
2 h, 95%
Tamm et. al. Angew. Chem. Int. Ed. 2007, 46, 8890.
Conclusion
- New (pre)catalysts are much more functional group tolerant and efficient.
- Bench top stable pre-catalyst has emerged (silanolate bound Mo complexes).
- The yields of cross-metathesis are generally moderate.
- RCAM and homodimerization are relatively mature.
- Three ways to drive the equilibrium of metathesis:
(1) reduced pressure, (2) precipitation and (3) molecular sieve
- Mechanism of some pre-catalysts is still unknown (tris-amido Mo complex).
- Promising in the area of ADIMET and Shape Persistent Macromolecules.
For reviews on: Alkyne Metathesis, see Zhang, Moore Adv. Synth. Catal. 2007, 349, 93.
RCAM, see Fürstner, Davies Chem. Commun. 2005, 2307.
Carbyne Complexes, Fischer et. al. 1988, VCH Verlagsgesellschaft
Handbook of Metathesis: Catalyst Development, Grubbs, Ch 1.11