O-Trimethylsilyl cyanohydrin

The addition of HCN to aldehydes or ketones produces cyanohydrins. This is an equilibrium reaction. For aldehydes and aliphatic ketones the equilibrium lies to the right therefore the reaction is quite feasible, except with sterically hindered ketones such as diisopropyl ketone. However, ketones ArCOR give poor yields, and the reaction cannot be carried out with ArCOAr since the equilibrium lies too far to the left. With aromatic aldehydes the benzoin condensation (16-54) competes. With oc,p-unsaturated aldehydes and ketones, 1,4 addition competes (15-33). Ketones of low reactivity, such as ArCOR, can be converted to cyanohydrins by treatment with diethylaluminum cyanide (Et2AlCN see OS VI, 307) or, indirectly, with cyanotrimethylsilane (MesSiCN) in the presence of a Lewis acid or base, followed by hydrolysis of the resulting O-trimethylsilyl cyanohydrin (52). The use of chiral additives in this latter reaction leads to cyanohydrins with good asymmetric... 

Htinig and coworkers found that carbanion 290 which is derived from O-trimethylsilyl-cyanohydrin reacted with carbonyl compounds to afford the corresponding a-siloxyketones through a 1,4-silyl migration (equation 181)440-442. 

Acyloins.1 Acyloins, both aliphatic and aromatic, can be prepared in good yield by reaction of Grignard reagents with O-trimethylsilyl cyanohydrins, which are readily available by reaction of cyanotrimethylsilane with aldehydes and ketones (4, 542-543). 

A nice example of the solvent-dependent dual reactivity of an electrophilic crypto-cationic species has been given by Hiinig et al. [663]. Ambident electrophilic a-enones react with nucleophiles such as the anion of the benzaldehyde O-(trimethylsilyl)-cyanohydrin (Nu ) in diethyl ether exclusively by 1,4-addition. In tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME), the 1,2-adduct is formed predominantly on the addition of HMPT or [12]crown-4 it is formed exclusively cf. Eq. (5-133). 

The alkylation chemistry of a considerable number of O-trimethylsilyl cyanohydrins derived from aryl and heteroaryl aldehydes has been reported by Hunig and coworkers. Tbe protected cyanohydrins are easily prepared by heating the aldehydes with trimethylsilyl cyanide in the presence of a Lewis acid. The use of dialkyl sulfates and tosylates as alkylating agents was so reported. Hata et alP failed to alkylate the anion of the adduct of trimethylsilyl cyanide and acetaldehyde, suggesting that the trimethylsilyl group is incompatible with the more basic anions derived from aliphatic aldehydes. Ficini et alP... 

Silyl ethers. Gold nanopaiticles ate found to be effective catalyst for derivatization of aldehydes by MesSiCN to afford O-trimethylsilyl cyanohydrins at room temperature. ... 

Amino-alcohols have been prepared efficiently by the reaction of O-trimethylsilylated cyanohydrins with Gngnard reagents,... 

Tetronic acids and -heto-y-butyrolactones are easily prepared by reaction of an O-trimethylsilylated cyanohydrin with a-bromo esters in the presence of a Zn-Cu couple in a Reformatsky-type reaction (Scheme 12). 2.73... 

Enantiomerically enriched O-trimethylsilyl cyanohydrins were transformed directly into O-acyl-cyanohydrins using various anhydrides or acid chlorides in the presence of a catalytic amount of Sc(OTf)3 (Scheme 12.40) [94]. 

Carbonyl Umpolung. When deprotonated with a strong base, O-(trimethylsilyl) cyanohydrins can function as effective acyl anion equivalents that can be used to convert aldehydes to ketones, and in the synthesis of 1,4-diketones, tricyclic ketones, and the highly sensitive a, -epoxy ketone functionality (eq 18). ... 

An equivalent of a homologous Claisen ester enolate rearrangement leading to 6,e-unsaturated esters has as its key step a Cope rearrangement of readily prepared, unsaturated O-trimethylsilyl cyanohydrins (Scheme 25). The overall process looks to be very efficient, the one drawback being the time and temperature requirements for the rearrangement (e.g. 195 C, 22 h). 

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