Reductions with hydrosilanes are methods used for hydrogenation and hydrogenolysis of organic compounds. The approach is a subset of ionic hydrogenation. In this particular method, the substrate is treated with a hydrosilane and auxiliary reagent, often a strong acid, resulting in formal transfer of hydride from silicon to carbon.[1] This style of reduction with hydrosilanes enjoys diverse if specialized applications.
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]
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 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]
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]
Trifluoroacetic acid, often used in these reductions, is a strong, corrosive acid. Some hydrosilanes are pyrophoric.
