2021 Theses Doctoral

Photoredox-Catalyzed Site-Selective Functionalization of Primary Amine Derivatives

Ashley, Melissa Ann

Given the prevalence of primary amines in biologically active molecules, an important area of research is devoted to creating methods to site-selectively functionalize their C(sp³)-H bonds. For simple aliphatic primary amines, many of these C-H bonds are chemically indistinguishable due to their similar electronics and sometimes, steric environments. Through strategic choice of activating group, site-selective functionalization at both α- and ẟ- positions is achieved. Exploiting inductive effect allows for a photoredox-catalyzed α-C(sp³)-H alkylation of trifluoromethanesulfonamides. In the case of trifluoroacetamides, functionalization is directed to a distal C(sp³)-H site via [1,5]-hydrogen atom transfer which results in a formal delta-aminomethylation and delta-cyanation. Lastly, by subjecting primary amines to an electron-rich benzaldehyde activating group, we leverage C-N bonds as a functional handle for deaminative radical cross-couplings.