Technical Library

The general equation for the silane reduction of alcohols to alkanes is illustrated below. The reaction proceeds best when the alcohol can lead to a stabilized carbenium ion. Thus, secondary and tertiary aliphatic alcohols and benzylic alcohols are readily reduced. Trialkyl substituted silanes are more reactive than dialkylsilanes and di- or triarylsilanes. Typical and highly-effective conditions for these reductions is treatment of the alcohol with the silane and trifluoroacetic acid in dichloromethane. Triethylsilane is often the silane of choice due to its ease of handling and high reactivity.22,23

The reduction of secondary alcohols with a silane and a protic acid does not occur. These reductions require the use of a strong Lewis acid such as boron trifluoride or aluminum chloride.24,25

Primary aliphatic alcohols are not reduced with silanes.26 Benzylic alcohols, on the other hand, are reduced under rather mild conditions to the corresponding toluene derivative.27

The reduction of a benzylic alcohol in the presence of benzyl ethers, a tetrahydrofuran and an acetal has been reported.28

As with the reduction of alcohols to alkanes the acid-catalyzed reduction of alkyl halides to alkanes requires the formation of a relatively stable carbenium ion intermediate that can accept the hydride from the silane. Thus, tertiary, secondary, allylic and benzylic halides lend themselves to this type of reduction. Under certain conditions primary halides can be reduced,29 but carbenium ion rearrangements are a problem.30

Trialkylsilanes, being better hydride donors, provide less rearranged product in these reductions than their dialkyl or monoalkyl counterparts.30

The reductions of organic halides with pentacoordinate hydridosilanes has been reported.31

The acid-catalyzed reduction of aldehydes with silane works best in the presence of water.32 In addition esters can be formed when an organic acid is the catalyst employed.33

An excellent alternative for the reduction of aldehydes to alcohols is through the use of triethylsilane with uncomplexed boron trifluoride in dichloromethane.34 This method gives the corresponding alcohol in high yield and very short reaction times.

An extremely high-yield reductive conversion of aldehydes to unsymmetrical ethers involves the reaction of the aldehyde with a trimethylsilyl ether in the presence of a silane and a strong Lewis acid, with trimethylsilyl triflate being especially efficient.35 Such silicon-based reductive-condensation chemistry should be applicable to combinatorial chemistry where product isolation is always a crucial issue.

Aromatic aldehydes can be fully reduced to the corresponding toluene derivative.34,36

The conversion of aromatic aldehydes to benzylic halides has also been shown.37-39 The best reducing agent for this seems to be tetramethyldisiloxane.

Under catalysis by fluoride ion aldehydes are reduced to the corresponding silyl ether of the alcohol. Hydrolysis of the silyl ethers provides the unprotected alcohols. Cesium fluoride has been shown to be an excellent promoter for these conversions,40,41 as have tetra-n-butyl ammonium fluoride (TBAF) and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF).42 This can also be used as a route to trimethylsilyl-protected alcohols from aldehydes.

The reduction of aldehydes to alcohols has also been carried out with polylmethylhydrosiloxane as the hydride source. In this case the work-up includes reaction with methanol to release the free alcohol.43

The selective reduction of aldehydes over ketones can be realized with polymethylhydrosiloxane as the reducing agent with fluoride ion-catalysis.44

Silanes have been used for the reduction of ketones to alcohols with excellent results.45 The reduction of ketones or aldehydes in the presence of acetonitrile and an acid provides an alkyl acetamide.33 The reduction of aldehydes to alkyl acetamides is also possible.33

In a similar manner the reduction of ketones and aldehydes to esters has been reported.33 This reaction is always accompanied with the formation of the symmetrical ether.

The reduction of aryl ketones (acetophenone derivatives) to the methylene is readily accomplished.46 Triethylsilane with titanium tetrachloride works best for this transformation, though other systems also work well.

The selective reduction of aryl ketones to alcohols over dialkyl ketones can be carried out with phenyldimethylsilane in the presence of cuprous chloride or cuprous acetate.47

The one-pot reduction of amides to aldehydes with diphenylsilane has been reported.48 This provides a potentially highly-useful, non-oxidative entry into aldehydes.

The reduction of acids and esters to alcohols with polymethylhydrogensiloxane occurs in good yields in the presence of titanium tetraisopropoxide49 or tetrabutylammonium fluoride.50 The reduction of esters has also been carried out with diphenylsilane and rhodium catalysis.51

The triethoxysilane reduction of esters to alcohols in high yields is possible.52 This transformation also takes place with PMHS as the reductant.53,54

The conversion of lactones to lactols was accomplished with a titanium-catalyzed reduction with PMHS.55

The reduction of imines to amines with trichlorosilane and dichlorosilane was reported. Dichlorosilane gave the best results.56

The reduction of oximes to alkoxyamines is accomplished with phenyldimethylsilane and trifluoroacetic acid.57

Not surprisingly the ionic reduction of suitable olefins, i.e. those which can generate a relatively stable carbenium ion, can be reduced by silanes in the presence of an acid catalyst. The ability to generate the carbenium ion is essential to the success of the reaction. For example, 1-methylcyclohexene is readily reduced to methylcyclohexane whereas cyclohexene itself is not reduced under the same and even more forcing conditions.58 The most common conditions for these reductions is with an excess of trifluoroacetic acid, a strong acid with a conjugate base of low nucleophilicity, and triethylsilane.59-63 Likewise, terminal olefins that are not styrenic in nature, and 1,2-disubstituted olefins are not reduced with silanes again due to the inability to form a suitable carbenium ion intermediate. On the other hand, the reduction of enol ethers, and similar olefins which can form good carbenium ions, is possible.62,64

The reduction of α,β-unsaturated carbonyls to their saturated counterparts is conveniently carried out with silanes in the presence of a rhodium or copper catalyst.65,66

Ojima and Kogure67 have shown that the reduction of α,β-unsaturated ketones or aldehydes with triethylsilane or ethyldimethylsilane gives 1,4-addition resulting in reduction of the double bond whereas diphenylsilane gives 1,2-addition and straight reduction of the carbonyl.

An example of the reduction of a styrenic double bond in the presence of another double bond and a ketone is shown below.68 The double bond of an α,β-unsaturated ketone was reduced with the triethylsilane/acid combination, though regeneration of the ketones was necessary.69

The reduction of a trisubstituted olefin in the presence of an ester was shown.70

The silane reduction of acetylenes to alkanes is not a practical approach to this transformation.71