Suzuki−Miyaura Cross-Coupling of Aryl Carbamates and Sulfamates: Experimental and Computational Studies

TLDR

A computational study providing the full catalytic cycles for these cross‑coupling reactions is described. The study uses the inexpensive, bench‑stable NiCl₂(PCy₃)₂ catalyst and computational modeling to map the full catalytic cycle for the cross‑coupling. The authors report the first Suzuki–Miyaura cross‑coupling of aryl O‑carbamate and O‑sulfamate groups, achieving good to excellent yields across a broad scope—including electron‑donating, electron‑withdrawing, ortho‑substituted, and heteroaryl substrates—while computational studies reveal a five‑centered oxidative addition and water‑stabilized Ni‑carbamate resting state, and they demonstrate the method’s utility in synthesizing polysubstituted aromatics of natural product and bioactive interest.

Abstract

The first Suzuki−Miyaura cross-coupling reactions of the synthetically versatile aryl O-carbamate and O-sulfamate groups are described. The transformations utilize the inexpensive, bench-stable catalyst NiCl2(PCy3)2 to furnish biaryls in good to excellent yields. A broad scope for this methodology has been demonstrated. Substrates with electron-donating and electron-withdrawing groups are tolerated, in addition to those that possess ortho substituents. Furthermore, heteroaryl substrates may be employed as coupling partners. A computational study providing the full catalytic cycles for these cross-coupling reactions is described. The oxidative addition with carbamates or sulfamates occurs via a five-centered transition state, resulting in the exclusive cleavage of the aryl C−O bond. Water is found to stabilize the Ni-carbamate catalyst resting state, which thus provides rationalization of the relative decreased rate of coupling of carbamates. Several synthetic applications are presented to showcase the utility of the methodology in the synthesis of polysubstituted aromatic compounds of natural product and bioactive molecule interest.