Development and Mechanistic Implications of Nickel Pre-Catalysts for Organic Synthesis

[摘要] Nickel catalysis is a versatile tool for constructing complex molecules, but a variety of operational challenges limit the wide spread use of these methods outside academic labs. The use of experimental and computational tools for understanding and developing technical improvements related to pre-catalyst design are described herein. An off-cycle pathway stemming from pre-catalyst activation of Ni(COD)2 for hydroarylation of alkynes via C-H functionalization has been identified. The use of computational methods has assisted in characterizing these complexes as potential off-cycle resting states and experimental support for this conclusion is described. Pre-catalyst adaptation by removing COD has allowed for rapid C-H functionalization at room temperature for a variety of structural manifolds. Additionally, a potential energy surface for nickel-catalyzed hydroarylation and a structure-activity relationship has been developed that uses computational data to predictive experimentally observed rates for nickel-catalyzed hydroarylations via C-H functionalization.Furthermore, a new class of N-heterocyclic carbene (NHC)–supported ¬Ni(0) pre-catalysts is described that display enhanced air-stability while retaining high reactivity. This is done through the employment of pi-acidic ligands that stabilize electron-rich Ni(0). The use of this strategy is applied to several NHC ligands of varying steric profiles. Their stability and reactivity are evaluated for reductive couplings and amination cross–couplings. To this end, structure-activity relationships are developed that have led to the design of air-tolerant and catalytically active NHC–Ni(0) pre-catalysts.

[发布机构] University of Michigan

[效力级别] Air-stable Nickel Pre-catalysts

[关键词] Nickel Catalysis;Air-stable Nickel Pre-catalysts;Computational and Experimental Mechanistic Studies of Nickel-catalyzed C-H Functionalization;Chemistry;Science;Chemistry