Abstract:

Construction of new C–C bonds between two fragments in the syntheses of natural products and pharmaceutically relevant compounds have been accomplished through transition metal-catalyzed cross-coupling (XC) and, more recently, cross-electrophile coupling (XEC) reactions. Specifically, nickel, a more sustainable base metal, has become more prevalent and attractive for the development of new XEC reactions due to the ability of nickel to access more oxidation states compared to palladium, allowing for the possibility of both radical and polar reactivities. We have conducted mechanistic studies of reactions involving alkyl alcohol derivatives, as well as developed new reactions, including 1) halogenation of alkyl alcohols using Grignard reagents, 2) radical clock experiments to probe the radical lifetime in the XEC reaction of 1,3-dimesylates, 3) XEC reaction of alkyl mesylates with allylic difluorides, and 4) deoxygenative coupling of alkyl mesylates with methyl tosylate to install methyl groups.