Sterically Hindered Ketones via Palladium-Catalyzed Suzuki–Miyaura Cross-Coupling of Amides by N–C(O) Activation

Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki–Miyaura cross-coupling of unconventional amide electrophiles by selective N–C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki–Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N–C(O) bond twist.