Merging hydrogen atom transfer processes with photoredox/nickel dual catalysis for the selective functionalization of C(sp3)-H bonds

University Of Pennsylvania, Philadelphia PA

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Abstract

Project Summary/Abstract The transformative impact of catalytic cross-coupling methods on the assembly of organic molecules cannot be overstated, as evidenced by their widespread adoption for the synthesis of both pharamecuticals and small molecule products. A recently developed paradigm-shifting cross-coupling method that employs both photoredox and base-metal catalytic cycles working in concert has enabled the formation of carbon-carbon bonds that were inaccessible via traditional cross-couplings. These dual catalytic reactions proceed under exceedingly mild conditions (room temperature and near-neutral pH) and with excellent functional group tolerance, enabling the cross-coupling of various prefunctionalized alkyl and aryl halide partners. The goal of the proposed research is to utilize a photocatalyzed hydrogen atom transfer (HAT) process for the selective activation of alkyl C?H bonds at room temperature and their subsequent functionalization within a base-metal catalyzed cross-coupling cycle. Intra- and intermolecular HAT cycles will be explored, enabling both the directed functionalization of unactivated C?H bonds as well as the utilization of inexpensive commodity chemicals as coupling partners. The use of polarity reversal catalysts will further increase the diversity of C?H bonds that can be functionalized within this dual catalytic cross-coupling manifold. The ability to engage ubiquitous alkyl C?H bonds in cross-couplings will allow for the rapid and streamlined assembly of complex molecules under mild conditions from a virtually limitless pool of alkyl precursors, while simultaneously minimizing waste and improving the sustainability of the process.