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

Org Lett. 2019 Oct 4;21(19):7976-7981. doi: 10.1021/acs.orglett.9b02961. Epub 2019 Sep 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.