# Sulfur-Fluoride Exchange (SuFEx) Reactions toward Nitrogen-Based Sulfur(VI) Compounds

> **NIH NIH R15** · POMONA COLLEGE · 2020 · $394,145

## Abstract

Project Abstract
Sulfonamides, sulfamides, and sulfamates are incredibly important compounds with therapeutic
applications against cancer, HIV, and microbial infections. Existing strategies to make these
nitrogen-based sulfur(VI) compounds are limited by the commercial availability of starting
materials and harsh reactions preventing late-stage functionalization. Sulfur-fluoride exchange
(SuFEx) chemistry is a promising new pathway to synthesize sulfonylated products from sulfur(VI)
fluorides and nucleophiles. However, the stability of sulfur(VI) fluorides compared to other halogen
analogues present challenges for synthetic applications. Herein, we propose the development of
new sulfur-fluoride exchange (SuFEx) reactions to synthesize nitrogen-based sulfonylated
compounds by activating sulfur(VI) fluorides with metal-based Lewis acidic salts and
organocatalysts. The proposed work is innovative because it seeks to develop attractive
alternatives toward introducing sulfonylated moieties into organic compounds by employing easy
to handle starting materials, cheap Lewis acid salts and organic-based catalysts. Successful
implementation of the research proposed herein will lead to novel one-step SuFEx
transformations toward S–N and S–O formation enabling the development of new, diverse
libraries for drug discovery. The first aim focuses on the development of calcium-mediated
activation of sulfamoyl fluorides and fluorosulfates to make sulfamides and sulfamates – a
critically underdeveloped class of sulfonylated compounds. This transformation will represent a
considerable advance over current methods that rely on starting materials that are challenging to
synthesize or isolate. The second aim seeks to understand the mechanism of Lewis-acid
activation of sulfur(VI) fluorides in SuFEx chemistry. Information gleaned from these kinetic and
computational studies will provide critical information towards understanding key intermolecular
interactions that govern the reaction, leading to new generation of SuFEx reactions. The third aim
will focus on the development of catalytic SuFEx reactions using Lewis acidic salts and basic
organocatalysts; establishing new modes to activate sulfur(VI) fluorides toward sulfonylated
compounds. The PI’s research has enhanced the research environment at Pomona College by
engaging undergraduate students in organometallic catalysis and synthetic research. The work
in this proposal will expose undergraduates to biomedically-relevant research with significant
impact in synthesis and medicinal chemistry.

## Key facts

- **NIH application ID:** 9965195
- **Project number:** 1R15GM134457-01A1
- **Recipient organization:** POMONA COLLEGE
- **Principal Investigator:** Nicholas D Ball
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,145
- **Award type:** 1
- **Project period:** 2020-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965195

## Citation

> US National Institutes of Health, RePORTER application 9965195, Sulfur-Fluoride Exchange (SuFEx) Reactions toward Nitrogen-Based Sulfur(VI) Compounds (1R15GM134457-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9965195. Licensed CC0.

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