Palladium-Catalyzed Aerobic Oxidative Spirocyclization of Alkyl Amides with Maleimides via & beta;-C(sp(3))-H Activation

An efficient method for the synthesisof bicyclic spirodiaminemolecules via & beta;-C(sp(3))-Hbond activation of aliphatic amides, followed by cyclization withmaleimides, has been developed. The reaction proceeds through an amide-directed & beta;-C(sp(3))-H bond activation of alkyl amidesand subsequent cyclization with maleimides. The methodology is highlycompatible with a wide variety of maleimides. Amides derived frombiologically active aliphatic and fatty acids were also found tobe highly compatible with the protocol. A palladacycle was synthesizedand found to be the active intermediate in this reaction. A plausiblereaction mechanism was also proposed to account for this spirocyclization.