Nickel Catalysis: Asymmetric Arylation of Quinolinium Ions and the Development of an Air-Stable Precatalyst

Abstract

Although both palladium and nickel were reported to catalyze cross-coupling reactions some four decades ago, palladium became the catalyst of choice for most chemists, due in part to the greater air stability of Pd(0) relative to Ni(0). Nevertheless, nickel is a desirable catalyst for two reasons. First, nickel is three orders of magnitude less expensive than palladium. Second, nickel offers reactivity distinct from palladium due in part to the difference in electronegativity between the metals—for example, palladium is more likely

to mediate C–H activation, while nickel more readily reacts with pi-systems, effecting cyclization reactions of olefins.

In this dissertation, we describe two projects that leverage these advantages. First, we discuss the application of a nickel-iminium activation mode to an enantioselective crosscoupling reaction between arylboroxines and quinolinium ions. This reaction allows access to enantioenriched 2-aryl-1,2-dihydroquinolines with unprecedented stereoselectivity. A necessary step in the optimization of this reaction was the use of an unusual precatalyst, [(methallyl)NiCl]2, instead of the more commonly used Ni(cod)2.

Second, we detail the development of [(TMEDA)Ni(o-tolyl)Cl], a modular, airstable nickel precatalyst. We believe this nickel source is a useful alternative to other nickel precatalysts reported in the literature. Due to the lability of TMEDA, this complex can be used in conjunction with mono- and bidentate phosphines, diimines, and NHC ligands, which is crucial to its success as a precatalyst in Suzuki–Miyaura, Buchwald–Hartwig, cyclization, and oxidative coupling reactions.