Computational Insights into the Rhodium(III)-Catalyzed Coupling of Benzamides and 1,6-Enynes via a Tunable Arylative Cyclization

A density functional theory (DFT) study has been conducted to elucidate the mechanism of the rhodium(III)-catalyzed C-H activation of O-substituted N-hydroxybenzamides and cyclohexadienone-containing 1,6-enynes. The impact of, different O-substituted internal oxidants (OPiv versus OMe) on the arylative cyclization (i.e., (N)-Michael addition versus -Michael addition) has been evaluated in detail. The ON addition pathway proceeded via a Rh(I) species, while Rh(III) remained unchanged throughout the (C)-Michael addition pathway. The Rh(III)/Rh(I) catalytic cycle in the (N)-Michael addition pathway was, different from those reported previously where the Rh(III)/Rh(V) catalytic cycle was favored for the Rh(III)-catalyzed C-H activation of O-substituted N-hydroxybenzamides. The first three steps were similar for the OPiv- and OMe-substituted substrates, which involved sequential N-H deprotonation, C-H activation (a concerted metalation deprotonation process), and 1,6-enyne insertion steps. Starting from a seven-membered rhodacycle, the alternative mechanism would be controlled by the OR substituent. When the substituent was OMe, the unstable seven-membered rhodacycle was readily coordinated by a double bond of the cyclohexadienone which enabled the -Michael addition reaction. However, the presence of an N-OPiv moiety stabilized the seven-membered rhodacycle through a bidentate coordination which facilitated the (N)-Michael addition process.