REGIOSELECTIVE AND ENANTIOSELECTIVE SYNTHESIS OF ALPHA-SILYL ALDEHYDES AND KETONES VIA SAMP RAMP HYDRAZONES/

An efficient, highly regio- and enantioselective methodology for the s ynthesis of alpha-silyl aldehydes and ketones 2 and 6 using two differ ent procedures was developed. Direct alpha-sily lation of the azaenola tes derived from SAMP/RAMP hydrazones 3 with various silyl trifluorome thanesulfonates resulted after oxidative removal of the chiral auxilia ry in highly enantiomerically enriched alpha-silyl aldehydes and keton es (R)- or (S)-2. Alternatively, hydrazones 5 derived from acetaldehyd e or methyl ketones were initially alpha-silylated followed by highly diastereoselective alpha-alkylation with suitable electrophiles. The l atter variant allows the regiocontrolled synthesis of alpha-silyl keto nes (S)-6 with high enantiomeric purity, not available by direct alpha -silylation of unsymmetrical ketone hydrazones. The absolute configura tion of the resultant alpha-silyl carbonyl compounds 2 and 6 was deriv ed from earlier mechanistic investigations of electrophilic substituti ons via deprotonated SAMP/RAMP hydrazones and was unambiguously assign ed by X-ray-crystallographical analysis of the alpha-silyl-SAMP hydraz one (S,R)-4c.