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LEWIS
ACID CATALYSIS IN ORGANIC SYNTHESIS
NOVEL REDUCTION OF ALCOHOLS
REDUCTIVE CLEAVAGE OF ETHERS
REDUCTIVE CLEAVAGE OF ARYL ALKYL ETHERS
DIRECT REDUCTION OF ACIDS
EXHAUSTIVE REDUCTION OF CARBONYL COMPOUNDS
B(C6F5)3-CATALYZED ALLYLATION OF BENZYLIC ALCOHOLS
B(C6F5)3-CATALYZED ALLYLATION OF PROPARGYLIC ALCOHOLS
B(C6F5)3-CATALYZED TRANS-HYDROSILYLATION OF ALKENES
TRANS-HYDROSILYLATION/TAMAO OXIDATION
Trans- and
Cis-SELECTIVE LEWIS ACID CATALYZED HYDROGERMYLATION OF
ALKYNES
Our
forth area of interest deals with the development of novel Lewis
acid-catalyzed transformations. We
have found that primary alcohols and ethers can effectively be
reduced to the corresponding hydrocarbons
by HSiEt3 in the presence of catalytic amounts of
B(C6F5)3. Classical
LA-mediated exhaustive reduction methods require employment of
suprastoichiometric amounts of Lewis acids and proceed via SN1
mechanism through the formation of a carbenium ion, which
determines the reactivity order: tertiary > secondary
>> primary. In
contrast, this novel catalytic reaction proceeds efficiently
with 1-5 mol% of B(C6F5)3
catalyst only, and exhibits a reverse substrate reactivity
pattern: primary >> secondary >> tertiary.
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We
have shown that primary alcohols and ethers can be effectively
reduced to the corresponding hydrocarbons
by HSiEt3 in the presence of catalytic amounts of
B(C6F5)3.
The secondary alkyl ethers,
underwent cleavage and/or reduction under similar reaction
conditions to produce either the silyl ethers or the
corresponding alcohol upon subsequent deprotection with TBAF.
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The
same reaction in the presence of excess hydrosilane allowed for
the formation of two hydrocarbon moieties, but only in the case
of bis-primary alkyl ethers.
Cleavage of bis-secondary alkyl ethers, phenyl ethers and
catechol acetals stopped at the formation of the corresponding
silyl ethers. This
method proved very efficient in deprotection of aryl alkyl
ethers. Thus,
various anisoles reacted almost instantly under virtually
neutral conditions at room temperature to quantitatively afford
phenyl silyl ethers, or the corresponding phenols, after
treatment with fluoride. [J.
Org. Chem. 2000, 65,
6179]
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Direct
exhaustive reduction of carboxylic acids is a challenging task,
as normally most methods require initial conversion of acid into
ester or other derivatives. However,
we have been able to achieve direct reduction of acids into a
methyl group by designing a sequential process that involved
dehydrocondensation of the acid with a silane to produce silyl
ester in situ. The
latter was further converted to bis-silyl acetal and then, via
successive reduction of a silyl ether to a hydrocarbon.
Interestingly, in most cases the reaction could be
stopped at any step by maintaining exact stoichiometry of
hydrosilane. For
example, we were able to convert alpha-naphthoic acid into
aldehyde in good yield in a one-step sequence. [J. Org. Chem.
2001, 66, 1672]
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We
also explored the possibility for exhaustive reduction of
carbonyl compounds. It
was found that various aldehydes, acyl halides, esters, and
anhydrides gave the corresponding hydrocarbons in high yields.
Reduction of dihydrocumarinones afforded ortho-alkyl
phenol derivatives, quantitatively.
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Furthermore,
we have developed an effective protocol for allylation of
secondary benzylic alcohol derivatives with allylsilanes in the
presence of catalytic amounts of B(C6F5)3.
Various
functionalized secondary benzylic acetates smoothly underwent
the allylation reaction under mild conditions to give the
corresponding allylation products in very high yields. [Org.
Lett. 2001, 3, 2705]
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Likewise,
B(C6F5)3-catalyzed allylation
of secondary propargylic alcohol derivatives with allylsilanes
proceeded efficiently affording a variety of 1,5-enynes in good
to high yields with a number of functionalities, such as nitro,
chloro, ester, and boronic ester, being tolerated under these
reaction conditions. [Org. Lett. 2004, 6,
1999]
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We
also found that various alkenes undergo smooth
hydrosilylation in the presence of B(C6F5)3 affording the
corresponding hydrosilanes in excellent yields.
Remarkably, no side polymerization processes, typical for the
traditional Lewis acid-catalyzed hydrosilylation, were observed.
Comparison of yields obtained using novel B(C6F5)3-catalyzed
and traditional AlCl3-mediated hydrosilylation methodologies
(yields in parentheses) clearly demonstrates the superiority
of this new protocol.
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Tolerance
of this method towards aryl-containing hydrosilanes allows
for its broad application for the synthesis of alcohols via
trans-selective hydrosilylation/Tamao-Fleming oxidation
sequence, complementary to the existing cis-selective
hydroboration/oxidation reaction. [J. Org. Chem. 2002, 67, 1936]
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In an effort to expand our hydrometalation methodology towards the employment of functionalized substrates, we focused on the hydrogermylation reaction. The reaction of ambident substrate bearing both an ether and alkyne moiety gives clean cleavage of the ether function with one equivalent of silane. Conversely, the same substrate, when treated with even an excess of germane, gives clean hydrogermylation in high yield with no detectable amounts of ether cleavage product.
[Org.
Lett. 2005, 7, 5191]
Encouraged by this result, we sought to examine the scope of substrates tolerable under the reaction conditions. It was found that alkyl- and arylgermanes worked equally well in the hydrogermylation of alkynes. Additionally, a variety of alkynes, such as ether-, trifluoromethyl-, and even furyl-substituted were efficiently employed in the reaction. Remarkably, bromo- and iodo-substitued arylalkynes were hydrogermylated in quantitative yield. The known radical hydrogermylation conditions are incompatible with these functionalities.
To account for the trans-selective hydrogermylation of simple alkynes, we proposed a mechanism involving the formation of a “germylium borate” complex. Reversible addition of the “germylium” species would give a vinyl cation. The regiochemistry of this step is governed by the relative stability of the formed cation. Finally, delivery of hydride by borate regenerates the Lewis acid and gives the trans-hydrogermylation product.
While investigating the functional group compatibility of the reaction conditions, we were amazed to find that the hydrogermylation of propiolates proceeded in high yield. Remarkably, in striking contrast to all known Lewis acid catalyzed hydrometalations, the reaction proceeded with exclusive cis-selectivity.
We believe the hydrogermylation of propiolates follows different mechanistic path than that for simple alkynes. Reversible coordination of the Lewis acid to the carbonyl oxygen of propiolate would generate a zwitterionic complex, which would abstract hydride from germane. The formed allenoate would be trapped by germylium from the least hindered face, cis to H, to give the product.
The synthetic utility of the formed vinylgermanes was demonstrated in their transformation to stereodefined vinyl halides via the known halodegermylation reaction. For the vinylgermanes bearing electron withdrawing groups (ester function), modified conditions were found.
[Org.
Lett. 2005, 7, 5191]
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