Divergent synthesis of two types of indolizines from pyridine-2-acetonitrile, (hetero)arylglyoxal, and TMSCN

Abstract

Herein we describe the divergent synthesis of two types of indolizines via construction of the pyrrole moiety from pyridine-2-acetonitriles, arylglyoxals, and TMSCN. While one-pot three-component coupling provided 2-aryl-3-aminoindolizines via an unusual fragmentation process, a sequential two-step assembly protocol with these starting materials allowed efficient access to a wide range of new 2-acyl-3-aminoindolizines through an aldol condensation–Michael addition–cycloisomerization process. The subsequent manipulation of 2-acyl-3-aminoindolizines enabled direct access to novel polycyclic N-fused heteroaromatic skeletons.