Organocatalytic Reaction Cascade

Significance

An organocatalytic asymmetric reaction cascade towards 3-substituted cyclohexyl­amines 4 is described. Self-sacrificing achiral amines 2 in combination with a chiral phosphoric acid catalyst have proven to promote the trans­formation of 2,6-diones 1 to cis-3-substituted cyclo­hexylamines 4 in moderate to excellent dia­stereo- and enantioselectivities. Overall, the triple cascade is believed to proceed via (1) an initial aldol reaction via an enamine intermediate, (2) a conjugate reduction of an iminium ion, and (3) a Brønsted acid catalyzed reductive amination. Hantzsch ester 3 serves as a hydride donor for the conjugate reduction and the reductive amination.