# Mild and Selective Cooperative-Base Mediated Hydrosilylations for Improved Drug Synthesis

> **NIH NIH R15** · WESTERN WASHINGTON UNIVERSITY · 2022 · $375,988

## Abstract

Project Summary/Abstract
PI: Gregory O’Neil
 Western Washington University
Title: Mild and Selective Cooperative-Base Mediated Hydrosilylations for Improved Drug Synthesis
Abstract: Reduction reactions are key transformations in the synthesis of both clinical and experimental drugs
used to treat various human diseases. Common reducing agents, however, can present certain hazards (e.g.
sensitivity to moisture and the release of flammable H2 gas) and/or require special handling and equipment.
Additionally, as the target molecules become more complex, selectivity requirements become more stringent
which drives the need for new easily performed and highly selective reduction protocols. This proposal describes
the use of organosilanes combined with cooperative-base activation to produce a mild, approachable, and
selective reduction method with which to access various biologically active molecules.
 Both substrate-controlled diastereoselective hydrosilylations and chiral base-mediated enantioselective
carbonyl reductions will be investigated. The intramolecularity of these reactions is also expected to render the
transformations chemoselective (Aim #1). Regioselective epoxide openings will be accomplished that may
feature newly designed silanes and/or Lewis base activators (Aim #2). All of these reactions are expected to
generate dioxasilinane products that can then be further functionalized to generate valuable synthetic
intermediates that would otherwise be challenging to prepare (Aim #3). This is to be achieved by pursuing the
following specific aims:
 1. Explore chemo-, regio-, and diastereoselective cooperative base-mediated intramolecular
hydrosilylations.
 2. Perform mechanism-based optimizations of intramolecular hydrosilylations.
 3. Investigate functionalization reactions of dioxasilinane intramolecular hydrosilylation products.
This work will have a significant positive impact on providing new and superior access to various important
synthetic intermediates through the combination of predictable selectivity, versatility, and mild reaction
conditions, as well as presenting significant training opportunities for undergraduate participants in various
research methods.

## Key facts

- **NIH application ID:** 10436072
- **Project number:** 1R15GM146215-01
- **Recipient organization:** WESTERN WASHINGTON UNIVERSITY
- **Principal Investigator:** Gregory W O'Neil
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $375,988
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436072

## Citation

> US National Institutes of Health, RePORTER application 10436072, Mild and Selective Cooperative-Base Mediated Hydrosilylations for Improved Drug Synthesis (1R15GM146215-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10436072. Licensed CC0.

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