α-Silyl Controlled Asymmetric Mannich Reactions of Acyclic Ketones with Imines

Enantiomerically pure α-dimethylthexylsilyl ketones (S)-1a - e were converted regio- and stereoselectively to the corresponding α-silylated trimethylsilyl enol ethers (Z,S)-2a - e. Stereoselective α-silyl controlled Mannich reactions with BF₃ · Et₂O activated benzylideneaniline afforded the α′-silylated α,β-disubstituted β-amino ketones 3a - e in anti/syn ratios up to 80/20 and with moderate to good yields (61-82%). The major diastereomers (S,R,S)-3a - e (de ≥ 96%) were converted to the α,β-disubstituted β-amino ketones (R,S)-4a - e in excellent yields (92-96%), diastereomeric (de ≥ 96%) and enantiomeric excesses (ee = 95-≥ 99%) by removal of the silyl group with NH₄F/n-Bu₄NF.

asymmetric synthesis - Mannich reaction - α-silyl ketones - imines - β-amino ketones