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.
