# Using Numerical Analysis Tools to Design and Study Chiral Catalysts

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $464,032

## Abstract

Project Summary:
 The ability to produce chiral, non-racemic compounds efficiently is central to both the medical chemistry
and process chemistry aspects of pharmaceutical synthesis. While a substantial number of useful reactions
now exist, many more are needed to more thoroughly access chemical space. The development of new
reactions often requires significant empirical screening to achieve a desirable outcome in terms of both
reaction yield and stereoisomeric purity. Therefore we are targeting, through a collaborative effort, a
comprehensive approach to streamline catalyst optimization. We will address the essential question of how
one might “design” an asymmetric catalyst. Our proposed plan explores how catalyst and substrate structure
interact to produce specific outcomes. Careful, classical mechanistic studies that reveal the fundamental
mechanistic steps of reactions will be combined with modern physical organic parameterization/modeling
techniques developed in the Sigman Group. The combination of these strategies will guide catalyst design and
exploration of reaction scope. The field of asymmetric catalysis has come to recognize that the accumulation of
weak, noncovalent interactions is critical in a myriad of enantioselective reactions. The unifying feature of the
Aims of this project is a framework for understanding these forces as they culminate in efficient and highly
selective catalysis. The elucidation of catalyst design strategies that can be adopted by the organometallic,
organic and biological communities is our goal. In this context, the three Aims of the proposal evaluate three
diverse modes of asymmetric catalysis. The first aim is focused on chiral anion catalysis where the non-
covalent interactions responsible for asymmetric catalysis have been historically difficult to define due to the
complexity of interrogating the substrate/catalyst contacts. We will exploit new technology developed in the
Sigman group aided through previous collaborative studies between the Toste/Sigman and Miller/Sigman labs
that allow mathematical relationships to be discovered, relating substrate and catalyst structure to physical
organic measurements. This methodology not only allows for effective prediction, and thus the design of better
performing catalysts, but also provides a contemporary, data-intensive approach to mechanistic study. In the
second aim, we increase the complexity by evaluating organometallic reactions in combination with chiral
anion catalysis (sometimes with two chiral elements) to develop a portfolio of new alkene difuntionalization
reactions that have been initiated within both the Toste and Sigman labs. In the final aim, we ask questions
pertaining to systems with greater dynamic aspects of both substrate and catalyst in the context of small
peptide-catalyzed processes studied in the Miller lab. These efforts will test the limits of the modeling
techniques as well as potentially impact the broad fields of directed evolution...

## Key facts

- **NIH application ID:** 9830655
- **Project number:** 5R01GM121383-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Scott J Miller
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,032
- **Award type:** 5
- **Project period:** 2016-12-15 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830655

## Citation

> US National Institutes of Health, RePORTER application 9830655, Using Numerical Analysis Tools to Design and Study Chiral Catalysts (5R01GM121383-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830655. Licensed CC0.

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