Regioselective synthesis of 2-substituted 3-diarylmethylenylpiperidines

A simple three-step synthetic routes toward 2-substituted 3-diarylmethylenylpiperidines 7 (Y = CN) and 8 (Y = allyl) starting with 3-diarylmethylenylpiperidines 9 is described. The process was carried out by the bromomethoxylation of skeleton 9 with NBS in MeOH at reflux for 2 h, regioselective α-dehydrobromination with DBU in THF at reflux for 10 h, and BF3·OEt2-catalyzed cross-coupling of the corresponding enamine with trimethylsilyl-based nucleophiles (TMS-Y) in DCM at rt for 2 h. α-Amino ester 18 and β-amino acid 19 are also synthesized via the simple three-step synthetic protocol.