# New Directions in Nickel and Photoredox Catalysis

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2024 · $391,570

## Abstract

Project Summary/Abstract
The discovery and manufacture of new life-saving medicines necessitates the development of new and
improved synthetic tools that can access complex, bioactive chemical structures in a selective and sustainable
manner. The proposed research program seeks to address this need by devising novel chemical reactions and
elucidating new principles of catalysis in the fields of transition metal and visible light photoredox catalysis.
The addition of saturated carbon atoms into chemical structures has been shown to confer improved bioactive
properties to drug candidates, prompting a need for the invention of improved C(sp3)–C bond-forming
reactions. Early work from our laboratory and others demonstrated that Ni and Ni/photoredox catalysis
present a versatile platform to generate and functionalize carbon-centered radicals in C(sp3)–C(sp2) cross-
coupling. These reactions are being increasingly adopted by chemists in academia and the pharmaceutical
industry. Nevertheless, important challenges and opportunities remain, which the current proposal seeks to
address. These include: 1) the development of cross-selective C(sp3)–C(sp3) coupling reactions, with the
ultimate goal of affording a route to joining two saturated ring systems that is as versatile as traditional cross-
coupling for the assembly of biaryl architectures; 2) the identification of modular chiral ligand frameworks for
enantioselective and catalyst-controlled diastereoselective coupling reactions; and 3) the design of strategies
that overturn common site-selectivity for C(sp3)–H/O/N functionalization of small bioactive molecules.
Whereas most effort in the field of Ni and Ni/photoredox catalysis has focused on reaction discovery, our
program will also advance the field through ligand design and mechanistic studies. We will study the impact of
novel and established ligand classes on the structure and reactivity of catalytically relevant oxidation states of
Ni (0/I/II/III) with the goal of improving the efficiency of existing methods and enabling the design of new
reactions. Finally, despite numerous advances in the field of chemical catalysis, direct homolytic activation of
strong and redox-inaccessible C–O, O–H, and N–H bonds present in abundant feedstock chemicals and late-
stage bioactive compounds remains an outstanding challenge. Our program is addressing this gap by
developing a strategy that makes use of visible light photoredox catalysis and the single-electron redox
processes of phosphines for the activation of N–H heterocycles and aliphatic and (hetero)aromatic alcohols in
new bond-forming reactions. Taken together, these efforts will provide valuable new reactions and
understanding for the chemistry communities engaged in the discovery and synthesis of biologically active
small molecules. This program will also provide a platform for the scientific training and professional
development of a team of graduate students, postdoctoral researchers, and undergraduate ...

## Key facts

- **NIH application ID:** 10813814
- **Project number:** 5R35GM126986-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Abigail Gutmann Doyle
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $391,570
- **Award type:** 5
- **Project period:** 2018-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10813814

## Citation

> US National Institutes of Health, RePORTER application 10813814, New Directions in Nickel and Photoredox Catalysis (5R35GM126986-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10813814. Licensed CC0.

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