Photoredox Catalysis in Organic Chemistry

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DESCRIPTION (provided by applicant): Over the past five years, visible light-mediated photoredox catalysis has emerged as a versatile new activation platform in organic synthesis. Ruthenium or iridium-based polypyridyl photoredox catalysts absorb light in the visible range to generate stable, long-lived excited states that may act as either single-electron oxidants or reductants. Due to their unique reactivity profile, photoredox catalysts have the capacity to enable challenging bond constructions that are not accessible under standard approaches. In a seminal 2008 disclosure, our lab described the asymmetric α-alkylation of aldehydes via the synergistic merger of photoredox catalysis and chiral amine organocatalysis; this powerful dual-catalysis strategy features the simultaneous generation of catalytic quantities of both reactive intermediates. Subsequent reports, from our group and others, have further established the remarkable complexity-building capabilities of photoredox catalysis, particularly when merged with organocatalysis. In this research proposal, we outline new directions for our photoredox-based research program. Each of the four aims proposed herein envisions a novel reactivity platform featuring a transient, photoredox-generated active species that may be productively harnessed for the synthesis of a menu of high-value functional motifs. In Aim 1, we propose to develop direct, one-carbon expanded variants of the Mannich, Michael, and aldol reactions via a novel 5π-electron intermediate species that is transiently generated from ketone or aldehyde precursors through synergistic organocatalysis and photoredox catalysis. Aim 2 leverages an α-amino radical species - generated in situ via photoredox catalysis - en route to valuable amine-containing scaffolds, including vicinal diamines and allylic amines. Aim 3 envisions the direct arylation of labile allylic and benzylic C-H bonds through synergistic thiol-based organocatalysis and photoredox catalysis, as a means by which to gain rapid access to diaryl methanes and vinyl-aryl methanes. Finally, in Aim 4, we propose to accomplish the photoredox-catalyzed decarboxylative functionalization of α-amino acids en route to valuable benzylic amine and alkyl amine motifs. In a key expansion of this project, we will explore opportunities for the development of an asymmetric variant for the synthesis of γ-amino aldehydes via merged photoredox and chiral amine-based organocatalysis.