Develepment of Nickel-Catalyzed Hydrofunctionalization Reactions of Hydrocarbons

Abstract

This thesis presents the development of nickel-catalyzed hydrofunctionalization of alkenes and alkynes employing various hydride sources and counter-electrophiles, substantiated by mechanistic investigations of nickel intermediates involved in the catalytic cycles. The first part of this thesis details the development of nickel-catalyzed hydroboration of terminal alkynes. In this reaction, pinacolborane functions as an efficient reducing agent for the nickel precatalyst, a hydride donor, and electrophilic boron source, thereby enabling an easy access to alkenylboronates via a highly atom-economical process. The optimized reaction conditions afford α-alkenylboronates with excellent regioselectivity and high yields across a broad range of terminal alkynes bearing various functional groups. Notably, the mild reaction conditions facilitate access to 1,1-borylsilyl olefins, which are otherwise synthetically challenging. A pivotal aspect of this study is the successful generation of catalytically active NiI species within the hydrofunctionalization—previously hindered by the elusive nature of low-valent nickel intermediates. In particular, the alkenylnickel(I) species was accessed through transmetallation between a NiI complex and a Grignard reagent, providing definitive evidence for its existence and involvment as an active catalytic intermediate. This observation is consistent with the isotope labeling experiments, which indicated the syn-addition of HBpin to the alkynes. The second part of this thesis concerns the development of an asymmetric hydroamidation of 1,1- borylsilyl-substituted olefins, affording β-amido-α-silylboronate esters with high enantioselectivity. In this reaction, dimethoxymethylsilane is used as the hydride source, while 1,4,2-dioxazol-5-one is employed as an effective nitrene precursor. The optimized reaction conditions employ a chiral bi- oxazoline ligand. The methodology exhibits a broad substrate scope, accommodating various substituted 1,4,2-dioxazol-5-ones and other silyl- and boryl-bearing olefins, which undergo the transformation efficiently. Interestingly, β-selectivity is likely governed by the steric and electronic properties of the dimetalloid moiety, despite the typically strong α-directing effects of such groups in nickel-catalyzed hydrofunctionalization reactions. The synthetic utility of the resulting β-amido-α- silylboronate esters is further demonstrated through diversification of the metalloid moieties.