Synthesis of Fused Tricyclic Amines Bearing Tetrasubstituted Carbons Using an Alkylation-Cyclization-Isomerization-3-aza-Cope Cascade Reaction.

Abstract

A new cascade reaction sequence that involves alkylation, cyclization, isomerization, and 3-aza-Cope rearrangement was discovered. The stereogenic centers of the starting piperidines were transferred to the bicyclic enamine products, and a range of electron-withdrawing groups on the alkyne moieties, from ketones to amides, were tolerated under the reaction conditions. The bicyclic enamines underwent trifluoroacetic acid (TFA)-mediated cyclization to form tricyclic amines bearing tetrasubstituted carbons.