Catalytic Asymmetric Construction of Halogenated Stereogenic Carbon Centers by Direct Vinylogous Mannich-Type Reaction

A catalytic asymmetric
vinylogous Mannich-type reaction of γ-halo-α,β-unsaturated N-acylpyrazoles and N-Boc-aldimines
was disclosed, which afforded an array of halogenated (F-, Cl-, and
Br-) allylic stereogenic carbon centers in high yields with good to
high regio-, diastereo-, and enantioselectivities. The brominated
product served as a suitable electrophile for common SN2 nucleophilic substitution and copper-mediated SN2′
allylic alkylation with metal reagents. The utility of present methodology
was demonstrated by the asymmetric synthesis of a common intermediate
toward the synthesis of two chiral 2,3-disubstituted piperidine pharmaceuticals.