# New Frontiers in Chemical Reactivity Via Catalytic Hydrogen Atom Transfer

> **NIH NIH R35** · RICE UNIVERSITY · 2022 · $377,546

## Abstract

PROJECT SUMMARY
Hydrogen atom transfer (HAT), or the movement of one proton and one electron simultaneously, is an
increasingly important element in synthetic methodology. While nature has made extensive use of HAT steps in
processes such as those performed by desaturase and mutase enzymes, synthetic chemists are just beginning
to realize the potential of this powerful, radical transformation. This MIRA proposal describes two important new
areas enabled by HAT that the PI will explore over the next 5 years: modular radical hydrogenation and
transpositional functionalization. The PI is prepared to make an impact in this important field from his mentored
career, where he designed catalytic dehydrogenation and dehydroformylation systems functioning via HAT. The
first area of research concerns development of a modular, stereoselective hydrogenation system able to
completely control the configuration and isotopic composition at each reduced center (Project 1). Preliminary
work by the PI has demonstrated radical hydrogenation can be achieved using cooperative hydrogen atom
transfer (cHAT), a mechanism where each hydrogen atom arrives from a separate catalyst, allowing for each
catalyst to be modified independently. One goal of this project is independent stereocontrol of each new
stereocenter though use of two asymmetric catalysts (Project 1a). This design will allow for enantioselective anti-
reduction, a currently impossible transformation. A simultaneous, independent goal builds on preliminary data
showing each catalyst receives its hydrogen atom from an orthogonal source, permitting different isotopes to be
predictably delivered in the same reaction (Project 1b). Together, this project area will provide a method to install
H, D, or T in any configuration starting from an unsaturated bond, selecting between all possible isotopologues
and stereoisotopomers via catalyst and reagent control. The second research area focuses on the development
of new mustase-like reactions, where functionality is regioselectively transposed in a 1,2-fashion to remodel
molecular architectures (Project 2). However, unlike mutase enzymes, these methods will exchange the
functional group during the transposition, allowing rapid diversification of complex molecules. Preliminary data
from the PI demonstrates this principle using vitamin B12 and Co(Salen) cocatalysts to achieve “remote
elimination”, where primary alkyl electrophiles are translated into a 2-alkenes with terminal methyl group. We
anticipate this approach will be general, allowing for transpositional C–X, C–N, C–O, and C–C bond-forming
reactions (Project 2a). In parallel, the ability of vitamin B12 to enantioselectively convert meso-epoxides and
aziridines to allylic alcohols and amines will be used to achieve enantioselective C–H functionalization of the
epoxides and aziridines (Project 2b). Together, the proposed research will leverage the unique reactivity of HAT
to deliver a suite of new catalytic reactions b...

## Key facts

- **NIH application ID:** 10440504
- **Project number:** 5R35GM142738-02
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Julian G West
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $377,546
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440504

## Citation

> US National Institutes of Health, RePORTER application 10440504, New Frontiers in Chemical Reactivity Via Catalytic Hydrogen Atom Transfer (5R35GM142738-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440504. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*