Construction of P-stereogenic Centres via Palladium/Chiral Norbornene Cooperative Catalysis

Phosphorus stereocenter, as a ubiquitous central chiral element, plays a crucial role in pharmaceuticals, materials science and asymmetric catalysis. As such, stereoselective construction of phosphorus stereocenters has become an important endeavour in organic synthesis. Herein we report a general and modular method for the construction of P-stereogenic centres via palladium/chiral norbornene cooperative catalysis-enabled desymmetrization/kinetic resolution process. It is a two-component annulation reaction that involves widely available aryl iodides and prochiral or racemic phosphinamides as the reactants. A wide variety of substrates bearing an assortment of functional groups (50 examples) are compatible with this method. Other features include a distinct enantiodiscrimination mechanism, excellent stereoselectivities and scalability. The obtained chiral P-stereogenic products bearing a common C–Br bond, which can be elaborated for the synthesis of new P-stereogenic compounds with diverse structural features. In addition, preliminary studies uncover the promising chiroptical properties of these P‑stereogenic cyclic phosphinamides. DFT calculations are performed to reveal non-covalent hydrogen bonding interaction is the origin of enantiodiscrimination during the desymmetrization process.