Download Organometallic Chemistry

Organometallic Chemistry
Worawan Bhanthumnavin
Department of Chemistry
Chulalongkorn University
Bangkok 10330, Thailand
Given as part of the 6th semester organic chemistry course
at the University of Regensburg (May 2008)
Under the ASEM-DUO Thailand 2007 exchange program
organoboron, organosilicon
Organoboron compounds
• Revise: what organoboron have you seen before?
boranes
Organoboron compounds
• vast array of C-C-forming reactions involving organoborons
• Here: focus on transfer reactions of C moieties from boron to
an adjacent C. Examples: transfer of CO, CN, carbanions
derived from dichloromethyl methyl ether and dichloromethane,
and allyl groups in reactions of allylic boranes with aldehydes.
Preparations
Reaction of Organoborons
™Carbonylation
• reaction of organoboranes with carbon monoxide
[(–):C≡O:(+) ], which is an ylide, gives rise to
3 possible rearrangements.
• Depending on reaction conditions, single, double, and triple
migrations of groups may occur leading, after appropriate
workup, to a variety of aldehydes and ketones as well as
primary, secondary, and tertiary alcohols.
Reaction of Organoborons
™Carbonylation
™Synthesis of Aldehydes and Primary Alcohols
• Addition of CO to trialkylboranes leads to the formation of an
ate-complex (structure A). Subsequent migration of an R
group to the CO ligand yields intermediate B. In the presence
of a mild reducing agent, such as lithium trimethoxyaluminum
hydride or potassium triisopropoxyborohydride, B is converted
to the mono-migration product C.
Reaction of Organoborons
™Carbonylation
™Synthesis of Aldehydes and Primary Alcohols
• Oxidation (H2O2) of C furnishes the corresponding aldehyde.
On the other hand, treatment of C with LiAlH4 followed by
oxidative workup produces the primary alcohol.
Reaction of Organoborons
™Carbonylation
™Synthesis of Aldehydes and Primary Alcohols
• To maximize utilization of valuable alkyl groups, alkenes used
for the transfer reaction are hydroborated with 9-BBN. The
resultant alkyl-9-BBN derivatives undergo selective migration
of the alkyl group when treated with CO in the presence of a
reducing agent.
• Ex. applying this sequence to 2-methylcyclopentene produces
trans-2-methylcyclopentane carboxaldehyde, with retention of
configuration of the migrating group.
Reaction of Organoborons
™Carbonylation
™Synthesis of Ketones
• If the carbonylation reaction is done in the presence of a small
amount of water at 100 °C, a second alkyl group migrates from
B to the adjacent carbon to furnish, after oxidative workup, the
corresponding ketone.
Reaction of Organoborons
™Carbonylation
™Synthesis of Ketones
• The use of thexylborane (1,1,2-trimethylpropylborane) as the
hydroborating agent permits
– (a) the synthesis of mixed trialkyboranes, and
– (b) cyclic hydroboration of dienes.
Reaction of Organoborons
™Carbonylation
™Synthesis of Ketones
• When followed by carbonylation, these hydroborationcarbonylation sequences generate a variety of
unsymmetrically substituted ketones and cyclic ketones,
respectively. Since thexyl moiety exhibits low migratory
aptitude in carbonylation, it serves as an anchor group.
Reaction of Organoborons
™Carbonylation
™Synthesis of Ketones
Reaction of Organoborons
™Carbonylation
™Synthesis of tertiary alcohol
• Carbonylation of trialkylboranes in the presence of ethylene
glycol results in migration of a second and a third alkyl group
to give, after oxidation, the corresponding tert-alcohols.
• Hydroboration of polyenes followed by carbonylation and
oxidation provides access to carbocyclic systems.
Reaction of Organoborons
™Cyanidation
• A useful alternative to carbonylation route to ketones and
trialkylmethanols from alkylboranes
• nitrile anion [(–):C≡N:] is isoelectronic with CO and also reacts
with R3B. However, the cyanoborate salts are thermally stable
and therefore require an electrophile such as benzoyl chloride
or trifluoroacetic anhydride (TFAA) to induce 1,2-migration.
Reaction of Organoborons
™Cyanidation
Reaction of Organoborons
™Cyanidation
• formation of ketones and trialkylmethanols occurs under
milder conditions than when using CO. thexyl group = anchor
group in the preparation of ketones.
• NaCN must be dry.
• excess of TFAA results in a third migration, after oxidation,
trialkylmethanols
Reaction of Organoborons
™Dichloromethyl Methyl Ether Reaction
• reaction of organoboranes with nucleophiles containing more
than one leaving group results in multiple migrations.
• Thus, on treatment of R3B with α,α-dichloromethyl methyl
ether (DCME) in the presence of a sterically hindered base,
such as Li-triethylmethoxide (LiOCEt3), all three groups are
transferred, and oxidation of the product affords the
corresponding tertiary alcohol.
• LiCCl2OMe is generated in situ from dichloromethyl methyl
ether with lithium triethylmethoxide.
Reaction of Organoborons
™Matteson’s boronic ester homologation
• Homologation of chiral alkylboronic esters with dichloromethyl
lithium introduces a chiral center while forming a C-C bond
• The required boronic esters are readily accessible from
Grignard reagents and trimethylborate or from lithium reagents
and triisopropylborate. Hydrolysis of resultant alkylboronic
esters gives (r)- or (s)-pinanediols furnish the stable (r)- or (s)pinanediol alkylboronic esters.
Reaction of Organoborons
™Matteson’s boronic ester homologation
• The chiral directing groups are pinanediols derived from
osmium tetroxide-catalyzed oxidation of (+)-α-pinene or (–)-αpinene with trimethylamine oxide or with NMO
• The (s) and (r) notations shown in the abbreviations refer to
the configuration of the chiral center in the α-chloroboronic
ester using the appropriate pinanediol.
Reaction of Organoborons
™Matteson’s boronic ester homologation
(s)-pinanediol
boronic ester
rearr. upon
warming
rapid
borate complex
borate complex
ZnCl2 catalyzes the rearrangement
giving improved diastereoselection
(1S)-1-chloroalkylboronic ester
sec-alkylboronic ester
secondary
alcohol in
(>97% ee)
• important feature of the boron ester homologation: the boronic ester E can
itself be used as a starting boronic ester so that the cycle can be repeated to
introduce a second chiral center.
Reaction of Organoborons
• Retrosynthetic analysis of homoallylic alcohol
™Brown’s Asymmetric Crotylboration
• β-methyl homoallylic alcohol moiety of both anti- and synconfigurations is a characteristic structural element of a
number of macrolides and polyether antibiotics.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• Reactions of crotylmetal (2-butenylmetal) reagents with
carbonyl substrates provide access to acyclic stereo- and
enantioselective syntheses of β-methyl homoallylic
alcohols.
• The alkene moiety can be further elaborated into aldehydes by
oxidative cleavage of the double bond, leading to aldol-type
products.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• Crotyl organometallics undergo 1,3-shifts of the metal at rt.
• For the stereocontrolled use of allylic organometallic reagents
in synthesis, it is important that the stereoisomeric
reagents not equilibrate under the reaction conditions and
add to C=O regioselectively and irreversibly.
• Of the various allylic organometallic reagents, allylboronic
esters and allyldialkylboranes are especially suited for
acyclic stereoselective syntheses of homoallylic alcohols.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• rate of interconversion of crotyl boron reagents varies with the
nature of the R groups on boron:
crotyldialkylborane > crotylalkylborinate > crotylboronate
crotyl-BR2
crotyl- BR(OR)
crotyl-B(OR)2
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• Crotylboronic esters (2-butenylboronates) undergo nearly
quantitative additions to aldehydes.
• prepared by reaction of crotyl potassium reagents derived
from cis- or trans-2-butene with n-butyllithium and potassium
tert-butoxide followed by addition of the trialkyl borates
thermally stable and
isolable at room temp
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• reactions of crotylboronic esters with RCHO is regioselective,
generating 2 new stereochemical relationships and potentially
4 possible stereoisomeric products. Thus, there are 2
stereochemical aspects:
enantioselection (Re- vs. Si-face addition) and
diastereoselection (syn vs. anti).
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• transfer of allylic moieties from B to C=O carbon proceeds via
rearrangement to form intermediate boronic esters C and D
• reaction is highly diastereoselective.
• (E)-crotylboronate reacts to give the anti-homoallylic alcohol
• (Z)-crotylboronate reacts to afford the syn-homoallylic alcohol.
• This behavior has been interpreted in terms of the
Zimmerman-Traxler chair-type transition state model.
• Because of the double bond geometry, coordination of the (E)crotylboronic ester places the Me preferentially equatorial,
whereas coordination of the (Z)-crotylboronic ester places the
Me axial, as illustrated in the cyclohexane chair-form transition
state conformations A and B, respectively. In both cases, the
R moiety of the aldehyde must occupy a pseudoequatorial
position to avoid steric repulsion by one of the OR substituents
on boron.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• Zimmerman-Traxler transition state model.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• The use of enantiopure allylic boranes in reactions with achiral
aldehydes results not only in high diastereoselection, but also
in high enantioselection.
• Pure (Z)- and (E)- crotyldiisopino campheylboranes can be
prepared at low temperature from (Z)- or (E)- crotylpotassium
and B-methoxydiisopinocampheyl borane, respectively, after
treatment of the resultant ate-complexes with BF3•OEt2.
• The B-methoxydiisopinocampheylboranes are prepared by
reacting (–)-diisopinocampheylborane, derived from (+)-αpinene, or (+)-diisopinocampheylborane, derived from (–)-αpinene, with methanol.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• reaction of the (Z)-crotyldiisopinocampheylborane derived from (+)α-pinene with aldehydes at –78 °C, followed by oxidative workup,
furnishes the corresponding syn-β-methylhomoallyl alcohols.
• Use of (Z)-crotyldiisopinocampheylborane derived from (–)-α-pinene
also produces syn-alcohols with 99% diastereoselectivity but with
opposite enantioselectivity, an example of reagent control.
Reaction of Organoborons
™Brown’s Asymmetric Crotylboration
• (E)-crotyldiisopinocampheylborane, from (+)-α-pinene, +
aldehyde gives anti-alcohol (95% enantioselectivity).
• (E)-crotyldiisopinocampheylborane, from (–)-α-pinene, with
aldehydes yields the enantiomeric anti-alcohols, also with 95%
enantioselectivity. By this approach, using cis-and trans-2butene and (+)-α-pinene and (–)-α-pinene, all four
stereoisomeric homoallyl alcohols may be obtained.
Additional References - organoboron
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Ramachandran, P. V.; Brown, H. C. “Organoboranes for syntheses
Washington, D.C. : American Chemical Society, 2001.
Thomas, S. E. “Organic synthesis : the role of boron and silicon” Oxford:
Oxford University Press, 1991.
Pelter, A.; Smith, K. “Borane reagents” London: Academic Press, 1988.
Smith, K. “Organometallic compounds of boron” New York: Chapman
and Hall, 1985.
Mikhaĭlov, B. M.; Bubnov, U. N. “Organoboron compounds in organic
synthesis” New York: Harwood Academic, 1984.
Brown, H. C. “Organic syntheses via boranes” New York: Wiley, 1975.
Zimmerman, H. E.; Traxler, M. D. J. Am. Chem. Soc. 1957, 79, 1920.
Li, Y.; Houk, K. N. J. Am. Chem. Soc. 1989, 111, 1236.