Scaffold Diversity through a Branching Double-Annulation Cascade Strategy: Iminium-Induced One-Pot Synthesis of Diverse Fused Tetrahydroisoquinoline Scaffolds

摘要

A branching double annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium induced one-pot double cyclization sequence involving Pictect-Spengler type cyclization has been developed for the first time. The salient features of this protocol are direct and rapid access to unprecedented diverse fused THIQ skeletons, metal/catalyst free, cleaner reaction profile, good to excellent yields and convenient approach. This catalyst-free domino process facilitates the double annulation with variety of scaffold building agents via two C-N and one C-X (X = C, N, O) bonds formation in a single step, under uniform reaction conditions. Furthermore, we reveal an unusual dual BDAC sequence leading to N-N linked isoquinoline dimer.