Mechanistic Understanding as a Driving Force for Developments in Nickel-Catalyzed Coupling Methods.

Abstract

Investigating the mechanism of nickel-catalyzed reductive couplings of aldehydes and alkynes has provided evidence of several potential metallacycle intermediates. Through a series of double-labeling experiments employing deutero-triethylsilane and tripropylsilane, the influence of multiple organometallic intermediates along the reactive pathway was investigated. The nature of both the catalyst structure and the reactant structure were found to directly effect the formation of complex metallacycles. To further refine the mechanistic hypothesis for the reductive coupling of aldehydes and alkynes, a preliminary kinetics profile was compiled using a series of initial rate studies. From these investigations, a mechanism is proposed beginning with a stable bis-aldehyde nickel complex in equilibrium with the active mixed π-component species. The application of an air-stable nickel-NHC catalyst system was explored in a number of coupling reactions. The catalyst system was found to be a versatile catalyst for a range of Kumada-Corriu coupling reactions, but found limited applicability to Buchwald-Hartwig couplings and the reductive coupling of aldehydes and alkynes. The synthesis of electron-rich catalyst systems, bearing a saturated NHC ligand, is also reported, as well as the synthesis of a functionalized nickel catalyst from commercially available and bench-stable starting materials.