# Mechanism-Guided Catalyst Development through Reaction Discovery Simulation

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $369,434

## Abstract

Project Summary
Advances in chemical synthesis provide access to complex biologically active structures that
are highly relevant as pharmaceuticals and analysis tools. High performance reactions that
allow selective formation of specific covalent bonds are usually achieved by first uncovering
their fundamental chemical reaction mechanisms, as these mechanistic details pave the way
for further experimentation. Especially in the areas of C-H functionalization, Lewis acid/base
chemistries, and stereoselective transformations, the discovery of mechanism is vital due to
the high difficultly level in achieving these reaction steps. Further development of these reaction
types will enable efficient construction of a wide variety of powerful therapeutics, signaling
probes, and natural products.
The proposed research will leverage first principles simulations to greatly accelerate catalyst
development for novel synthetic reactions. The Zimmerman group's recently developed
reaction pathway discovery tools are especially well-positioned for this task, being able to
reveal unexpected reaction pathways as well as intuitive paths, giving deep insight into the
atomistic details of reactivity. In collaboration with numerous reaction development groups,
these tools have already been used to reveal principles for several classes of catalysts, and
have even allowed new catalyst structures to be designed. Application of these methods to the
proposed transformations (Ni-based C-H functionalization, macrolide glycosylation by chiral
organocatalysts, Lewis-acid catalyzed carbonyl-olefin metathesis, and oxidative enzymatic
transformations) will give the basic scientific insight needed to enable challenging synthetic
steps.
In summary, the proposed development of catalysts for highly selective transformations will
enable synthesis of a variety of scientifically and therapeutically relevant molecules, with
profound implications for the treatment and study of human health.

## Key facts

- **NIH application ID:** 10186775
- **Project number:** 5R35GM128830-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Paul Zimmerman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $369,434
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186775

## Citation

> US National Institutes of Health, RePORTER application 10186775, Mechanism-Guided Catalyst Development through Reaction Discovery Simulation (5R35GM128830-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10186775. Licensed CC0.

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