Rhodium-Catalyzed C–H Activation of Phenacyl Ammonium Salts Assisted by an Oxidizing C–N Bond: A Combination of Experimental and Theoretical Studies

TLDR

Rhodium(III)-catalyzed C–H activation using oxidizing directing groups is a mild, redox‑economic strategy that has so far been limited to N–O or N–N bonds, while cleavage of an oxidizing C–N bond for carbocycle synthesis remains unprecedented. This work designs α‑ammonium acetophenones bearing an oxidizing C–N bond as substrates for Rh(III)-catalyzed, redox‑neutral C–H activation. Experimental and DFT studies reveal that the Rh(III)-cataly.

Abstract

Rh(III)-catalyzed C–H activation assisted by an oxidizing directing group has evolved to a mild and redox-economic strategy for the construction of heterocycles. Despite the success, these coupling systems are currently limited to cleavage of an oxidizing N–O or N–N bond. Cleavage of an oxidizing C–N bond, which allows for complementary carbocycle synthesis, is unprecedented. In this article, α-ammonium acetophenones with an oxidizing C–N bond have been designed as substrates for Rh(III)-catalyzed C–H activation under redox-neutral conditions. The coupling with α-diazo esters afforded benzocyclopentanones, and the coupling with unactivated alkenes such as styrenes and aliphatic olefins gave ortho-olefinated acetophenoes. In both systems the reactions proceeded with a broad scope, high efficiency, and functional group tolerance. Moreover, efficient one-pot coupling of diazo esters has been realized starting from α-bromoacetophenones and triethylamine. The reaction mechanism for the coupling with diazo esters has been studied by a combination of experimental and theoretical methods. In particular, three distinct mechanistic pathways have been scrutinized by DFT studies, which revealed that the C–H activation occurs via a C-bound enolate-assisted concerted metalation–deprotonation mechanism and is rate-limiting. In subsequent C–C formation steps, the lowest energy pathway involves two rhodium carbene species as key intermediates.