Harnessing Dual Reactivity of N-Chloroamides for Cascade C-H Amidation/Chlorination of Indoles under Cobalt-Catalysis: Overriding Hofmann Rearrangement Pathway Leading to Aminocarbonylation

Org Lett. 2024 Dec 13;26(49):10523-10528. doi: 10.1021/acs.orglett.4c03925. Epub 2024 Nov 27.

Abstract

Herein, we have developed a Cp*Co(III)-catalyzed cascade C-2 amidation/C-3 chlorination of indoles by leveraging the dual functionality of N-chloroamides at ambient temperature. This protocol avoids the aminocarbonylation pathway that may result from the C-H functionalization of isocyanates formed via a potential Hofmann rearrangement of N-chloroamides. In fact, this represents the first example of directed C-H amidation using N-chloroamides as amidating agent. The control experiment indicated that the C-2 C-H amidation occurs prior to C-3 chlorination. Additionally, chloro functionality has been effectively utilized for the construction of C-S and C-N bonds, thereby expanding the molecular diversity of the synthesized compounds.