Palladium-Catalyzed Aerobic Oxidative Spirocyclization of Alkyl Amides with Maleimides via β-C(sp 3 )-H Activation.

An efficient method for the synthesis of bicyclic spirodiamine molecules via β-C(sp 3 )-H bond activation of aliphatic amides, followed by cyclization with maleimides, has been developed. The reaction proceeds through an amide-directed β-C(sp 3 )-H bond activation of alkyl amides and subsequent cyclization with maleimides. The methodology is highly compatible with a wide variety of maleimides. Amides derived from biologically active aliphatic and fatty acids were also found to be highly compatible with the protocol. A palladacycle was synthesized and found to be the active intermediate in this reaction. A plausible reaction mechanism was also proposed to account for this spirocyclization.