Tantalum Catalyzed\nHydroaminoalkylation Enables a\nTelescoping Catalytic Reaction Sequence for the Synthesis of Benzoannulated\nIndolizidines and Quinolizidines

The synthesis of benzoannulated indolizidines and quinolizidines\nis described through a telescoping reaction sequence featuring hydroaminoalkylation\nand nickel-catalyzed C–N bond coupling. An <i>in situ</i> generated tantalum (V) ureate catalyst is used to form new Csp<sup>3</sup>Csp<sup>3</sup> bonds between saturated <i>N</i>-heterocycles and <i>ortho</i>-chlorostyrene enabled by\nthe α CH bond activation of the amine. The addition\nof a nickel CN coupling catalyst generated from Ni(COD)<sub>2</sub> and DPPF to the reaction mixture allowed for cyclization.\nOur method leverages the regiodivergent branched and linear products\naccessed from <i>N</i>-heterocycle and styrene combinations,\nwhich are uniquely achieved by our tantalum catalyst to produce new <i>N</i>-heterocycle framework derivatives. Total isolated overall\nyields of up to 86% were achieved in a single pot. These advances\nhighlight alternative bond disconnections that enable direct access\nto distinct new <i>N</i>-heterocycle derivatives through\nearly transition metal catalyzed hydroaminoalkylation.