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

• Published in: Organometallics 2024-10, Vol.43 (20), p.2397-2402
• Main Authors: Zheng, Cameron H. M., Esslinger, Carla A., Dressler, Ole F., DiPucchio, Rebecca C., Ezhova, Maria B., Schafer, Laurel L.
• Format: Article
• Language: English
• ISSN: 0276-7333; 1520-6041
• DOI: 10.1021/acs.organomet.4c00281

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.