# Mechanistic Studies at the Frontiers of Catalysis

> **NIH NIH R35** · STATE UNIVERSITY OF NY,BINGHAMTON · 2022 · $207,746

## Abstract

Project Summary: Our research program investigates reaction mechanisms in asymmetric
organocatalysis and palladium catalyzed cross-coupling reactions. We utilize 13C and 2H kinetic isotope
effects (KIEs) in combination with theoretical calculations as design tools to evaluate fine details of the
transition state (TS) of the rate-determining step (RDS) under unmodified reaction conditions. Our
studies in the area of asymmetric organocatalysis (2013-present) have resolved long-standing debates,
uncovered novel mechanistic pathways, and probed origins of enantioselectivity in a wide variety of
reaction types. In 2018, NIH funding enabled us to expand our research program to the study of
palladium catalyzed cross-coupling reactions – an area of catalysis that is central to medicinal
chemistry. We have discovered that the magnitude of 13C KIE is highly sensitive to minor changes in
the carbon-palladium distance at the TS of the RDS – allowing us to distinguish between competing
pathways and probe the ligand environment at the metal center, all under catalytic conditions. Finally,
we have developed a novel methodology that utilizes symmetric reactants to obtain this information at a
fraction of the time and effort of traditional KIE approaches.
 This MIRA proposal seeks to further expand our research program to include new modes of
catalysis at the frontier of modern-day organic synthesis: (a) palladium catalyzed C-H bond-activation
and functionalization, and (b) nickel metallophotoredox catalysis. Over the next five years, our goal is to
establish our combined experimental and theoretical approach as the state-of-the-art to gain atomistic
understanding of the mechanistic underpinnings of these reactions. We chose these two areas to
expand our research program for two reasons – (a) new reaction discovery has far outpaced
mechanistic understanding of these reactions, and (b) our discoveries in palladium catalyzed cross-
coupling chemistry strongly indicate that our approach is ideally suited to resolve key mechanistic
questions in these contemporary areas of catalysis.
 The overall vision of our research program is to develop probes that can rapidly evaluate the
mechanism of catalytic reactions. We seek to change the paradigm that rigorous mechanistic
understanding follows new reaction discovery. We envision that the high-resolution mechanistic insight
that is delivered by our studies will inspire the discovery of new and more robust catalytic methods that
will enable organic synthesis.

## Key facts

- **NIH application ID:** 10406643
- **Project number:** 1R35GM145320-01
- **Recipient organization:** STATE UNIVERSITY OF NY,BINGHAMTON
- **Principal Investigator:** Mathew J Vetticatt
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $207,746
- **Award type:** 1
- **Project period:** 2022-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10406643

## Citation

> US National Institutes of Health, RePORTER application 10406643, Mechanistic Studies at the Frontiers of Catalysis (1R35GM145320-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10406643. Licensed CC0.

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