Transition metal-catalyzed cross-coupling reactions have revolutionized the
synthesis of small molecules for applications including medicinal chemistry,
agrochemistry, and materials science. The versatility of cross-coupling reactions is
due in part to the modular library of bond-breaking and bond-forming steps
accessible to a transition metal catalyst. Although this technology has resulted in
powerful methods for C–C and C–heteroatom bond formation, certain desired
transformations are limited by a high barrier elementary step or even a lack of the
necessary elementary step. In this talk I will discuss two distinct mechanistic
approaches to designing catalytic cross-coupling cycles that meet remaining
synthetic challenges in organic chemistry. First, photoredox catalysis will be shown to
integrate radical mechanisms–such as halogen abstraction-radical capture and
bimolecular homolytic substitution (SH2)–into first-row transition metal-catalyzed
reactions, delivering a Cu-catalyzed C–N cross-coupling at room temperature and an
Fe-catalyzed C–C cross-coupling to form quaternary carbons. Second, nontrigonal
phosphorus compounds will be discussed as an alternative to transition metal
catalysts to enable elusive deoxygenative transformations via P(III)/P(V) redox
cycling, including reductive functionalization of nitroarenes and stereoinvertive
deoxyfluorination of alcohols. I will present both the discovery and optimization of
these synthetic methods, as well as the mechanistic investigation of their underlying
catalytic cycles.