# A New Strategy for Cross-Coupling Chemistry Enabled by Base-Promoted Electron Transfer

> **NIH NIH F32** · COLORADO STATE UNIVERSITY · 2021 · $65,994

## Abstract

ABSTRACT
There is an important need to develop novel synthetic methodology that enables efficient access to valuable
fragments in pharmaceutical research using abundantly available reagents. With this goal in mind, many modern
advances have applied technologies such as transition metal catalysis, photocatalysis, or electrochemistry; in
contrast, this proposal draws mechanistic inspiration from these approaches while using only cheap inorganic
Lewis basic salts to promote challenging and novel coupling reactions. The long-term goal of this proposal is to
develop alternative cross-coupling reactions using Lewis bases as promoters to provide synthetic chemists new
tools to assemble pharmaceuticals. These advancements would be extremely valuable to drug discovery
chemists and provide a cost-effective route to complex drug fragments. To address this need, novel and general
Lewis base-promoted cross-coupling methodologies enabled by highly reducing silane-derived species are
proposed. Three specific transformations are described, including the reductive coupling of activated arenes
with organosilanes, carbonyl derivatives, and alkyl electrophiles. The successful development of the processes
outlined in this proposal will introduce a practical route to functionalized benzylic amines, ethers, and
diarylmethanes that are ubiquitous in biologically active compounds. Finally, the direct reduction of carbon-
halogen bonds will enable the late-stage modification of commercial drugs to allow for intense structure-activity
relationship studies. This proposal advances strategies inspired by modern technology using simple common
reagents in a straightforward approach to access valuable drug fragments in a mild and efficient manner to
ultimately accelerate drug discovery and improve human health.
 To achieve the overall goal of this proposal, we have outlined a rigorous training plan. The specific aims
outlined in this proposal describe three reductive coupling processes involving base-promoted reductive arylation
of alkyl electrophiles and carbonyl derivatives. The reagents and starting materials in these processes are
abundantly available, inexpensive, and practical, which will allow for the rapid uptake of this methodology. Key
mechanistic investigation through successful implementation of this training plan will allow for elucidation of other
novel coupling reactions and expansion of the initial discovery scope. The chemistry department at Colorado
State University is an excellent environment for successful training because of the collaborative atmosphere
between world-renowned organic chemists who are leaders in their respective fields. CSU’s stat-of-the-art
facilities will enable the unhindered development of the chemistry proposed. Furthermore, CSU has a variety of
educational resources including instructional coaching services, professional development, and writing
workshops. These important resources will be assets to the implementation of the training pl...

## Key facts

- **NIH application ID:** 10141586
- **Project number:** 1F32GM140567-01
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Tyler Wayne Reidl
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141586

## Citation

> US National Institutes of Health, RePORTER application 10141586, A New Strategy for Cross-Coupling Chemistry Enabled by Base-Promoted Electron Transfer (1F32GM140567-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141586. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*