Asymmetric Synthesis of Methylphenidate and Quinolizidinones by Addition of Aldehydes to Piperidine-Based Conjugated N -Acyl-iminium Ions

The synergistic effect of Lewis acids and MacMillan organocatalyst allows the α-regioselective and enantioselective α-amidoalkylation of piperidine derivatives with enolizable aldehydes. The potentiality of the synthetic method is illustrated by a short asymmetric synthesis of the eutomer of the blockbuster drug Ritalin and by a concise formal synthesis of 1-alkyl-4-substituted quinolizidine alkaloids.