New precursors for diverse radical reactions enabled by potent photoreductants

NIH RePORTER · NIH · R01 · $293,745 · view on reporter.nih.gov ↗

Abstract

PROJECT SUMMARY/ABSTRACT Radical intermediates generated through chemoselective single electron reduction have broad utility in the development of valuable synthetic transformations. As a consequence, photoredox catalysis, which induces single election transfer with exceptional selectivity for radical pathways, has shown great promise as an enabling technology in biomedical research. However, the design underpinning current photoredox catalysts limits the accessible reduction potentials and excludes numerous abundant feedstocks. The selective generation of radical intermediates from substrates inert towards conventional photoredox catalysis is a long- standing challenge with no general solutions. This proposal is based on the discovery that electrochemistry can generate new radical anion photocatalysts that are exceptionally potent excited state reductants but retain the selectivity of typical photoredox catalysts. We will study how these new catalysts can be exploited to develop radical coupling reactions infeasible with modern synthetic tactics. The three specific aims of this research center on exploring distinct but interwoven aspects of this new catalytic platform. Aim 1. We are exploring the ability to generate and exploit the reactivity of aryl radicals from aryl chlorides Aim 2. We are exploring the ability to engage carbonyl compounds in reductive radical coupling reactions Aim 3. We are exploring operationally simple strategies to access radical anion photocatalysts These methods address long-standing challenges in a fundamental class of organic reactions, reductions. These new catalytic systems will offer an expanded and diversified pool of starting materials from which the next generation of drugs and molecular probes will be discovered.

Key facts

NIH application ID
10422271
Project number
1R01GM146063-01
Recipient
UNIVERSITY OF WISCONSIN-MADISON
Principal Investigator
Zachary Kimble Wickens
Activity code
R01
Funding institute
NIH
Fiscal year
2022
Award amount
$293,745
Award type
1
Project period
2022-04-05 → 2027-01-31