Regio- and Enantioselective Synthesis of α-Silyl Aldehydes and Ketones via SAMP/RAMP Hydrazones

An efficient, highly regio‐ and enantioselective methodology for the synthesis of α‐silyl aldehydes and ketones 2 and 6 using two different procedures was developed. Direct α‐silylation of the azaenolates derived from SAMP/RAMP hydrazones 3 with various silyl trifluoromethanesulfonates resulted after oxidative removal of the chiral auxiliary in highly enantiomerically enriched α‐silyl aldehydes and ketones (R)‐ or (S)‐2. Alternatively, hydrazones 5 derived from acetaldehyde or methyl ketones were initially α‐silylated followed by highly diastereoselective α‐alkylation with suitable electrophiles. The latter variant allows the regiocontrolled synthesis of α‐silyl ketones (S)‐6 with high enantiomeric purity, not available by direct α‐silylation of unsymmetrical ketone hydrazones. The absolute configuration of the resultant α‐silylcarbonyl compounds 2 and 6 was derived from earlier mechanistic investigations of electrophilic substitutions via deprotonated SAMP/RAMP hydrazones and was unambiguously assigned by X‐ray‐crystallographical analysis of the α‐silyl‐SAMP hydrazone (S,R)‐4c.