One-pot two-step organocatalytic asymmetric synthesis of spirocyclic piperidones via wolff rearrangement-amidation-Michael-hemiaminalization sequence

Abstract

A highly enantioselective organocatalytic Wolff rearrangement–amidation–Michael– hemiaminalization stepwise reaction is described involving a cyclic 2-diazo-1,3-diketone, primary amine and α,β-unsaturated aldehyde. Product stereocontrol can be achieved by adjusting the sequence of steps in this one-pot multicomponent reaction. This approach was used to synthesize various optically active spirocyclic piperidones with three stereogenic centers and multiple functional groups in good yields up to 76%, moderate diastereoselectivities of up to 80:20 and high enantioselectivities up to 97%.