Carbanions from protected cyanohydrins

In the benzoin condensation, one molecule of aldehyde serves as an electrophile. If a carbanion is generated from protected cyanohydrins, a-aminonitriles or dithioacetals, it can react with electrophiles such as alkyl halides, strongly activated aryl halides or alkyl tosylates to form ketones. Amongst other electrophiles which are attacked by the above carbanions are heterocyclic A -oxides, carbonyl compounds, a,p-unsaturated carbonyl compounds, a,3-unsaturated nitriles, acyl halides, Mannich bases, epoxides and chlorotiimethyl derivatives of silicon, germanium and tin. 

The mechanism of the benzoin condensation, as depicted in Scheme 1, suggested that anions derived from a protected aldehyde cyanohydrin should function as nucleophilic acylating reagents. The use of protected cyanohydrins as carbanion equivalents has been studied by Stork and by Hunig and has found wide applicability in chemical synthesis. Such species may serve as either acyl anion equivalents or homoenolate anions. ... 

Intramolecular alkylations of nitrile-stabilized carbanions have been used to synthesize large rings such as those with 10 and 14 members. Tsuji and coworkers carried out a synthesis of the macrocy-clic antibiotic zearalenone by this route. As shown in Scheme 70, conversion of either of the protected cyanohydrins (144) or (145) to the corresponding dianions, resulting from deprotonation at the benzylic positions and a to the nitrile groups, gave the same cyclization product (146) in excellent yields. Dianion formation (i) provided control of the conformation of the side chain (ii) protected the ester from nucleophilic attack and (iii) appeared to increase the rate of the intramolecular cyclization. 

Heteroatom-stabilized Carbanions. Heteroatom-stabilized and allylic carbanions serve as homoenolate anions and acyl anion equivalents, e.g. a-anions of protected cyanohydrins of aldehydes and Q ,/3-unsaturated aldehydes are intermediates in general syntheses of ketones and Q ,/3-unsaturated ketones (eq 36). Allylic anions of cyanohydrin ethers may be a-alkylated (eq 37) or, if warmed to —25°C, may undergo 1,3-silyl migration to cyanoenolates which may be trapped with TMSCl. Metalated Q -aminonitriles of aldehydes are used for the synthesis of ketones and enamines (eq 38). Similarly, allylic anions from 2-morpholino-3-alkenenitriles undergo predominantly a-C-alkyl-ation to give, after hydrolysis, a,/3-unsaturated ketones (eq 39). ... 

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