Tantalum Catalyzed Hydroaminoalkylation Enables a Telescoping Catalytic Reaction Sequence for the Synthesis of Benzoannulated Indolizidines and Quinolizidines

Abstract

The synthesis of benzoannulated indolizidines and quinolizidines is described through a telescoping reaction sequence featuring hydroaminoalkylation and nickel-catalyzed C–N bond coupling. An in situ generated tantalum (V) ureate catalyst is used to form new Csp³─Csp³ bonds between saturated N-heterocycles and ortho-chlorostyrene enabled by the α C─H bond activation of the amine. The addition of a nickel C─N coupling catalyst generated from Ni(COD)₂ and DPPF to the reaction mixture allowed for cyclization. Our method leverages the regiodivergent branched and linear products accessed from N-heterocycle and styrene combinations, which are uniquely achieved by our tantalum catalyst to produce new N-heterocycle framework derivatives. Total isolated overall yields of up to 86% were achieved in a single pot. These advances highlight alternative bond disconnections that enable direct access to distinct new N-heterocycle derivatives through early transition metal catalyzed hydroaminoalkylation.