Regio-, Diastereo- and Enantioselective Synthesis of Piperidines with Three Stereogenic Centers from Isoxazolinones by Palladium/Iridium Relay Catalysis

Piperidines are currently the most frequently used heterocycles in the development of new pharmaceuticals. A straightforward efficient stereo- and regioselective asymmetric access to chiral polysubstituted piperidines creating multiple stereogenic centers is often still a challenge. Herein we report a rapid approach towards trisubstituted piperidines, which is notable for the use of a readily accessible isoxazolinone starting material and for creating three stereocenters in a single step. 3,4-Dihydropyridines, which are probably formed by a Pd-catalyzed cycle via a decarboxylative oxidative addition of the substrates, appear to be useful intermediates in this relay catalysis, in which Ir acts as enantioselective hydrogenation catalyst to form the valuable chiral heterocycles under mild conditions.