# Phenonium ions as control elements for the synthesis of chiral small molecules

> **NIH NIH R35** · UNIVERSITY OF MINNESOTA · 2020 · $352,689

## Abstract

Project Summary
 The goal of this proposal is to develop new synthetic methods for the rapid and precise construction of
chiral small molecule building blocks. The focal point of the chemistry described is the use of the phenonium ion
as a control element to surmount current synthetic limitations associated with stereo- and regiocontrol.
Consequently, this reactive intermediate enables the synthesis of benzylic and homobenzylic stereocenters,
which are important motifs found in many pharmaceutical agents.
 Various phases of this proposal concern expanding upon preliminary results from our laboratory for the
development of new methods to generate phenonium ions from unconventional starting materials. In each case,
new methods for addressing fundamental synthetic limitations will be obtained as well as a deeper fundamental
understanding of phenonium ion formation and reactivity. Execution of the chemistry described will enable
modular access to small molecule building blocks of relevance to drug discovery programs, e.g., chiral
heterocycles.
Relevance to public health:
 The vast majority of pharmaceutical candidates that make it to market are structurally complex, as defined
by the presence of sp3 carbons and stereocenters. Many drug molecules contain common architectures such as
benzylic and/or homobenzylic stereocenters. New methods that enable streamlined and modular access to these
motifs are, therefore, very important. Supporting this program would result in new synthetic approaches to chiral
small molecules containing benzylic and/or homobenzylic stereocenters from simple, readily-available starting
materials. In so doing, unsolved challenges related to stereo- and regiocontrol will also be addressed.

## Key facts

- **NIH application ID:** 10027148
- **Project number:** 1R35GM137920-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Nicholas James Race
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,689
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027148

## Citation

> US National Institutes of Health, RePORTER application 10027148, Phenonium ions as control elements for the synthesis of chiral small molecules (1R35GM137920-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10027148. Licensed CC0.

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