Development of cross coupling reactions with earth abundant metals

Abstract

The ability to prepare complex molecules has been advanced and enabled by crosscoupling reactions as exemplified by the 2010 Nobel Prize being awarded to the progenitors of palladium catalyzed cross-coupling technology. This is a powerful approach to bond formation that has been utilized in fine chemical synthesis, the agro and pharmaceutical industries, material/polymer preparation, and natural product synthesis. The problem our society is facing is that a majority of the transition and main group metals that are used in cross-coupling reactions are being depleted. The 40 year development of cross-coupling reactions has centered on precious metals (Pd, Pt, Rh, Ru, Ir, Os, & Au), in part due to their high functional group compatibility. Unfortunately, cross-couplings with precious metals is not sustainable. There is an ever growing need to develop new sustainable methods that employ earth abundant metals. The focus of this dissertation is my progress in the development of cross-coupling reactions with earth abundant 1st row transition metals. Two approaches are being pursued: 1) tandem/iterative cross couplings of titanacycles as a means to modularly form two bonds in a single reaction vessel, and 2) dual catalysis for the nickel catalyzed cross-coupling of in situ generated carbon radicals. It is shown that the titanacyclopropene has been coupled with Weinreb amides to synthesize various enones regioselectively. The work is extended to couple second electrophile (Lewus acid activated benzaldehyde) to modularly synthesize tetrasubstituted furan in moderate to good yields. At last the dual catalytic approach has been successfully utilized to couple aryl/alkyl halide with aryl/alkyl nitriles to synthesize ketones in good yields by using nickel and titanium catalyst. These synthesized enones, furans and ketones are complex building blocks valued in medicinal chemistry, library preparation, and natural product.