Non-Organometallic Partners as Radical Precursors for the Diversification of Dual Catalytic Cross-Coupling Processes

University Of Pennsylvania, Philadelphia PA

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Abstract

? DESCRIPTION (provided by applicant): The goal of the research proposed is to facilitate the construction of organic molecules by exploring unconventional reagents for cross-coupling and exploiting the unique attributes of such reagents. This will be accomplished by employing a recently developed, paradigm-shifting approach to cross-coupling involving a dual catalytic cycle. The two cycles, a photoredox catalytic cycle and a cross-coupling cycle, working in concert, will facilitate a single electron transmetalation protocol, allowing cross-coupling under mild conditions and, with the appropriate ligand, high levels of enantioselectivity via stereoconvergent transformations. In particular, methods to do so from inexpensive, bench-stable, commodity nonmetallic organic precursors will be sought. A process using such materials would be robust, cost-effective, and scalable, leading to a facile transition from the academic setting to a process development facility. Employing the dual catalytic systems that have proven effective in studies on the cross-coupling of organotrifluoroborates, the protocol will be extended to non-organometallic bulk source materials, namely hydrazines and sulfinate salts. Studies on these commodity materials will focus on practical methods of effecting radical formation under photoredox conditions and assessing their viability in being funneled into the base metal catalytic cycle. Organocatalysts and inexpensive inorganic materials will be explored as potential photocatalysts to enhance the sustainable profile of developed processes. Photoflow-based technologies and strategies will be examined as a means of enhancing scalability and effectivity. Diverse electrophilic coupling partners will be examined, and stereoconvergent processes will be developed to access enantioenriched alkyl substructures. This protocol will be transformative in enabling unprecedented C-C bond construction via cross-coupling from nonconventional, inexpensive coupling partners.