Deaminative vinylation and arylation cross-coupling reactions

Abstract

This thesis focuses on nickel-catalyzed vinylation and arylation cross-coupling reactions via C-N bond activation. Chapter 1 describes a vinylation method that was inspired by an analogous alkylation. This method takes advantage of mild reaction conditions and commercially available alkene and alkyne starting materials. This reaction proceeds through a regioselective hydroboration step to form an organoboron intermediate that then participates in the cross-coupling reaction. Excitingly, this reaction has a high functional group tolerance. Regarding the vinylated products, this reaction can install both non-styrenyl groups and tolerates alkyl and benzylic pyridinium salts overcoming limitations of prior methods. We propose this reaction to proceed through a Ni(I)/Ni(III) catalytic cycle based on radical clock and ring-opening experiments. This work was published in Organic Letters. ☐ Chapter 2 describes the development of a deaminative reductive cross-coupling reaction using aryl chlorides and alkyl pyridinium salts. This method aims to utilize the more abundant and challenging aryl chlorides in an efficient cross-coupling reaction with unactivated alkyl pyridinium salts. Utilizing High-Throughput Experimentation (HTE), we found 4,4’-di-tert-butyl-2,2’-bipyridine ligand to give a decent yield with a nickel (II) chloride hexahydrate catalyst with sodium chloride as the additive. Further examination of the catalyst system is needed to produce efficient yields with a range of aryl chlorides.