# Development of Sulfur-Based Reactions with Translational  Applications

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $323,656

## Abstract

Project Summary/Abstract
Cross-coupling reactions provide the most reliable and modular means to diverse chemical space, enabling the
discovery of novel pharmaceuticals and elucidation of critical biological pathways. Seminal efforts spanning the
last century have led to the development of a variety of metal-catalyzed cross-coupling reactions that allow
efficient chemical bonds formation. However, these powerful chemical transformations still have shortcomings.
Endeavors in developing novel coupling methodologies could address the identified challenges in the chemical
literature. More importantly, they can be deployed to rapidly synthesize structurally and topologically complex
compounds from accessible starting materials. Our research laboratory is seeking to invent new synthetic
approaches to address this identified gap in the cross-coupling literature, specifically focusing on methodology
development with the nonmetal element sulfur, one of the most abundant and inexpensive starting materials with
versatile oxidation states (–2 to +6). We propose high valent sulfur complexes can enable diverse coupling
modes in either stoichiometric or catalytic fashions. This proposal is organized into three sections with the goal
of addressing current limitations in synthetic methodology and affording the ability to rapidly generate diverse
and complex small molecule libraries. The first portion of this proposal illustrates a plan for sulfurane-mediated
hindered C(sp2) and C(sp3) coupling via S(IV) to S(II) reduction. The second section illustrates how nonmetal
sulfur (S(VI) to S(IV)) can provide a general and practical solution to alkyl boronate synthesis, especially for
unprotected alkyl boronic acids. The last part of this proposal argues that persulfuranes have the potential to
mediate synthetically valuable C–F bond formation, even possibly in a catalytic manner (S(VI) ↔ S(IV)). These
described methods will enable facile access to scaffolds of interest for medicinal chemistry and biological
evaluation. The biological properties of several families of compounds will be further investigated through our
already established collaborations. Taken together, these innovative new synthetic modes could address the
synthesis of challenging and medicinally relevant chemical scaffolds.

## Key facts

- **NIH application ID:** 10180743
- **Project number:** 1R01GM141088-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Tian Qin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $323,656
- **Award type:** 1
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180743

## Citation

> US National Institutes of Health, RePORTER application 10180743, Development of Sulfur-Based Reactions with Translational  Applications (1R01GM141088-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10180743. Licensed CC0.

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