Organobismuth Compounds As Universal Precursors for Oxidative and Reductive Radical Group Transfer via Photoredox Catalysis

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PROJECT SUMMARY/ABSTRACT This research project will develop organobismuth compounds (bismines) as universal reactive precursors for the generation, transfer, and functionalization of carbon and heteroatom-centered radicals. Taking advantage of the wide, tunable nature of photochemical oxidants, initial efforts will identify oxidants capable of efficient oxidation of bismines to their corresponding radical cations. Following potentially reversible mesolytic cleavage, these radical cations would afford carbon- or heteroatom centered radicals which would then add to a range of radical acceptors (olefins, arenes, imines, azodicarboxylates) to yield functionalized products. Although early investigations will focus on group transfer from stoichiometric amounts of bismine, the longer term goal of this endeavor is a dual catalytic photoredox and bismuth- mediated platform for generation of radicals from stable feedstock precursors (organosilanes, boronic acids, silyl ethers). In parallel to investigations of oxidative radical generation from bismines, we will explore addition of photoreductively generated alkyl radicals to bismines to generate transient bismuthanyl radicals. Inspired by literature precedent of ligand abstraction from bismuth by radical species, in addition to reversibility of radical additions to earlier pnictogens, we will develop bismines as reagents for the functionalization of alkyl radicals for form C(sp2)–C(sp3), C(sp3)–C(sp3), C–O, and C–N bonds. Although this would also initially be pursued in a stoichiometric fashion, insights gained from bismine turnover from oxidative functionalization would inform design of a catalytic variant of this transformation in the longer term. After developing both oxidative and reductive radical generation and transfer reactions using bismines, we will use mechanistic and reactivity insights gained to develop bismines as a platform for the difunctionalization of olefins via convergent carbobismuthinated intermediates. This intermediate could be accessed through three distinct mechanistic pathways followed by intramolecular ligand migration: (1) trapping of an bismine radical cation by an olefin (2) trapping of a bismine by an olefin radical cation (3) trapping of a bismine by a triplet sensitized olefin. Intermediate bismines could then engage in the functionalization modes developed in both oxidative and reductive radical reactivity to afford large range of possible difunctionalized products. In the longer term, this would also be developed into a catalytic protocol. Taken together the three proposed aims will develop bismines as novel, unified entry points to canonical reactive intermediates for radical generation, functionalization and transfer. All three methods will advance the mission of the NIH by enabling the swift, modular synthesis of medicinally relevant building blocks and compounds for drug discovery and tool development. Additionally, the fundamental organobismuth chemistry developed in pursuit of these aims will prove enabling to others utilizing organobismuth reagents in catalysis, development of antifungal compounds, and materials science by greatly increasing the variety of available scaffolds and synthetic approaches thereto.