Reductions with hydrosilanes

Some alcohols are reduced to alkanes when treated with hydrosilanes in the presence of a strong Lewis acid. Brønsted acids may also be used. Tertiary alcohols undergo facile reduction using boron trifluoride etherate as the Lewis acid.[2] Primary alcohols require an excess of the silane, a stronger Lewis acid, and long reaction times.[3]

Skeletal rearrangements are sometimes induced.[4] Another side reaction is nucleophilic attack of the conjugate base on the intermediate carbocation.[5] In organosilane reductions of substrates bearing prostereogenic groups, diastereoselectivity is often high. Reduction of either diastereomer of 2-phenyl-2-norbornanol leads exclusively to the endo diastereomer of 2-phenylnorbornane.[6] None of the exo diastereomer was observed.

Allylic alcohols may be deoxygenated in the presence of tertiary alcohols when ethereal lithium perchlorate is employed as a source of Li⁺.[7]

Reductions of alkyl halides and triflates gives poorer yields in general than reductions of alcohols. A Lewis or Bronsted acid is required.[8]

Aldehydes and ketones

Polymeric hydrosilanes, such as polymethylhydrosiloxane (PHMS), may be employed to facilitate separation of the reduced products from silicon-containing byproducts.[9][10]

Enantioselective reductions of ketones may be accomplished through the use of catalytic amounts of chiral transition metal complexes.[11] In some cases, the transition metal simply serves as a Lewis acid that coordinates to the ketone oxygen; however, some metals (most notably copper) react with hydrosilanes to afford metal hydride intermediates, which act as the active reducing agent.[12]

In the presence of rhodium catalyst 1 and rhodium trichloride, 2-phenylcyclohexanone is reduced with no diastereoselectivity but high enantioselectivity.[13]

Esters

Esters may be reduced to alcohols under conditions of nucleophilic activation with caesium or potassium fluoride.[14]

Aldehydes undergo hydrosilylation in the presence of hydrosilanes and fluoride. The resulting silyl ethers can be hydrolyzed with 1 M hydrochloric acid. Optimal yields of the hydrosilylation are obtained when the reaction is carried out in very polar solvents.[10]

${\displaystyle {\ce {{\mathit {n}}-C10H21CHO}}+{\color {Blue}{\ce {PhMe2Si}}}{\ce {H->[{\ce {TBAF}}][{\ce {rt}}]{\mathit {n}}-C10H21CH2O}}{\color {Blue}{\ce {SiMe2Ph}}}}$

(13)

${\displaystyle {\begin{array}{lr}{\ce {Solvent}}&{\ce {Yield}}(\%)\\\hline {\ce {CH2Cl2}}&1\\{\ce {THF}}&9\\{\ce {Me2NCOH}}&56\\{\ce {DMPU}}&89\\{\ce {HMPA}}&91\end{array}}}$

Hydrosilanes can reduce 1,1-disubstituted double bonds that form stable tertiary carbocations upon protonation. Trisubstituted double bonds may be reduced selectively in the presence of 1,2-disubstituted or monosubstituted alkenes.[15]

Aromatic compounds may be reduced with TFA and triethylsilane. Substituted furans are reduced to tetrahydrofuran derivatives in high yield.[16]

A synthesis of (+)-estrone relies on selective hydrosilane reduction of a conjugated alkene as a key step. The ketone carbonyl and isolated double bond are unaffected under the conditions shown.[17]

Acetals, ketals, and aminals are reduced in the presence of hydrosilanes and acid. Site-selective reduction of acetals and ketals whose oxygens are inequivalent have been reported—the example below is used in a synthesis of Tamiflu.[18]

Other functional groups that have been reduced with hydrosilanes include amides,[19] and α,β-unsaturated esters[20] enamines,[21] imines,[22] and azides.[23]