In addition to the more common approaches to the silylation of organic functional groups with chloro, amino, and related silanes, it is possible to react the Si-H bond with alcohols accompanied by the loss of dihydrogen in a process known as dehydrogenative silylation.72 The dehydrogenative silylation requires catalysis beyond the normal acid or base. The dehydrogenative silylation approach can offer advantages particularly in cases of the more hindered organosilane protecting groups such as the TES and TBS groups. In the case of the extremely popular and useful TBS protecting group the standard TBS-Cl used for the protection of alcohols is an air-sensitive solid with a melting point of 91 °C and a boiling point of 120 °C making it difficult to handle.22 In the case of the TES group, triethylsilane is readily available as a highly useful reducing agent used in organic synthesis and is the most common precursor to the TES-Cl.73 The silylation of alcohols and carboxylic acids with triethylsilane or phenyldimethylsilane was accomplished under the influence of (p-cymene)ruthenium dichloride catalysis (Eqs. 46 & 47).74 Other dinuclear ruthenium catalysts were also shown to be effective in the dehydrogenative silylation of carboxylic acids albeit at a slower reaction rate.
The Grubbs catalyst 11 effects the dehydrogenative silylation of alcohols of all types. In this approach phenyldimethylsilane and diphenylmethylsilane proved to be more reactive than either triethylsilane or tert-butyldimethylsilane (Eq. 48). The release of dihydrogen during the reaction was shown to cause some hydrogenation of olefinic functional groups, but no evidence of cross metathesis was found.75
Tert-butyldimethylsilane was shown to very selectively silylate the primary alcohol of methyl glycosides when catalyzed by Pd(0) in the form of a colloidal solution of palladium in DMF (Eq. 49).76 The method complements that of other approaches in many instances.
The dehydrogenative silylation of alcohols, amines and carboxylic acids was shown to be possible with only a 5 mol% loading of 10% Pd on charcoal (Eq. 50).77 It could be assumed that olefins would not be tolerated under these conditions unless the dihydrogen byproduct were to be effectively removed.
The gold xantphos complex 12 can effect the dehydrogenative triethylsilylation of alcohols with a strong preference for primary alcohols. It was also shown to triethylsilylate an alcohol in the presence of an aldehyde and ketone without reduction of the aldehyde or ketone groups, respectively (Eqs. 51 & 52).78
The strong Lewis acid, tris(pentafluorophenyl)boron, was shown to catalyze the dehydrogenative silylation of primary, secondary, tertiary, and phenolic alcohols, including some very highly hindered ones (Eq. 53).79 The catalyst has been shown to function by activation of the Si-H bond by bonding to the hydridic hydrogen making the silyl group highly electrophilic. The study emphasizes the use of triphenylsilane as the silylating agent, but demonstrates the use of triethylsilane, tert-butyldimethylsilane and phenyldimethylsilane as well. However, the more highly hindered tribenzylsilane and triisopropylsilane failed to react. Diols can be protected in cyclic form via dehydrogenative silylation with diphenylsilane (Eq. 54).79
The sequential dehydrogenative silylation of dialkylsilanes can result in the formation of mixed dialkydialkoxysilanes. This was shown with dirhodium tetraacetate or Pd/C catalysis (Eqs. 55 & 56).80 A similar approach was employed to prepare phenylalkoxysilanes, Ph(RO)SiH2, with the preferred catalyst being bis(hexafluoroacetylacetonato)copper (II). In some cases the dialkoxysilane was formed in these reactions.81,82
A benzostabase protection of an aniline based on 1,2-bis(dimethylsilyl)benzene was prepared by dehydrogenative coupling and successfully used in the preparation of the amine-protected 4-lithioaniline, 13 (Eq. 57).47,48
A solid-phase tert-butyldiarylsilyl, TBDAS, protecting group was developed for the purpose of solid-phase synthetic applications. The group, similar in many respects to the TBDPS group was found to be quite robust (Eq. 58).83 Fluoride ion in the form of TBAF or TAS-F in THF was found to cleave the protected alcohol in high yield.
A dehydrogenative silylation approach was used in a classical resolution of the two enantiomers of cyclic silane 15. Thus, (-)-menthol was reacted with racemic 14 and the resulting diastereomers separated by flash chromatography. The purified diastereomers could be cleanly reduced with DIBAL-H with complete retention at silicon (Eq. 59).84
The enantiomerically highly enriched silane 17 was used in a dehydrogenative silylation for the kinetic resolution of racemic secondary alcohols containing a donor group. A series of 2-pyridylethyl alcohols was subjected to dehydrogenative silylation conditions to provide the diastereomeric mixture of silylated alcohols and the enantiomerically enriched alcohol as illustrated by the conversion of 16 (Eq. 60).85-87 A similar investigation was undertaken in the kinetic resolution of b-donor functionalized benzyl alcohols (Eq. 61).88 Finally, a similar approach was applied to the kinetic desymmetrization of racemic diols.89