# A General Co-Catalytic Methodology for Enantioselective Photoredox Radical Cation Reactions

> **NIH NIH F32** · UNIVERSITY OF WISCONSIN-MADISON · 2020 · $65,310

## Abstract

PROJECT SUMMARY
 The transformation of alkenes into precursors for natural products is an important step in
many pharmaceutical processes. In many cases, only one enantiomer of a natural product or
pharmaceutical compound has the intended biological activity. Other enantiomers may be
inactive, and thus a waste of material, or cause dangerous unwanted side-effects. However, the
synthesis of enantiopure bioactive molecules can be difficult and costly. Enantioselective variants
of some of the most important molecular complexity-building reactions, like the Diels-Alder
cycloaddition and hydrofunctionalization reaction, are limited in substrate scope and scale-up
ability. The polarity inverted radical cation reaction greatly expanded the substrate scope and the
advent of visible light photocatalysis provided a cost-effective method to catalyze these reactions.
Few asymmetric photocatalytic methodologies have been developed with limited application to
natural product and pharmaceutical synthesis. The proposed research will develop an asymmetric
co-catalytic methodology general to photocatalyzed radical cation reactions. This methodology
will take advantage of ion-pair formation between the radical cation and a counteranion in solution.
Chiral hydrogen bond donor co-catalysts that bind the counteranions will provide a means to
optimize the asymmetric reaction independent of the photocatalyst yielding unparalleled control
over the reaction rate and selectivity. This methodology will be initially optimized for the
photoinitiated radical cation Diels-Alder cycloaddition. Separate optimization of the photocatalyst
and the hydrogen bond donating co-catalysts will provide a synthetically useful asymmetric
transformation. Application of this methodology to the synthesis of enantiopure indolines will
provide clear evidence of its applicability in the synthesis of biologically important compounds and
scaffolds. The proposed methodology will be translated to the asymmetric photocatalysis of
alkene hydrofunctionalization to provide enantiopure value-added products. The successful
development of this asymmetric co-catalytic methodology will provide chemists with the means to
rapidly synthesize enantiopure compound libraries for rapid drug screening and development.
The training I receive through the proposed research and mentorship from Professor Tehshik
Yoon will provide me with an extensive background in organic synthesis and methodology
development. Through combination with my background in spectroscopy and photochemistry I
will develop an independent career as an R1 university professor focused on the use of
mechanistic study to develop novel, pharmaceutically useful organic transformation.

## Key facts

- **NIH application ID:** 10001979
- **Project number:** 5F32GM134611-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Wesley Bryan Swords
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001979

## Citation

> US National Institutes of Health, RePORTER application 10001979, A General Co-Catalytic Methodology for Enantioselective Photoredox Radical Cation Reactions (5F32GM134611-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10001979. Licensed CC0.

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