# Harnessing Alkyl Amines and Alkyl Alcohols in Cross-Coupling Reactions

> **NIH NIH R35** · UNIVERSITY OF DELAWARE · 2020 · $385,458

## Abstract

The search for new medicines requires the discovery of new molecules, and the increasing awareness that
saturated atoms correlate to successful drug development mandates that these molecules be three-
dimensional. This increasing importance of saturated carbons in bioactive molecules provides exciting
opportunities for the invention of new cross-coupling methods and new alkyl electrophiles from widely
abundant starting materials. This research will focus on alkyl alcohols and amines for their unique and exciting
potential as cross-coupling electrophiles. Alkyl amines and alcohols have traditionally been seen as synthetic
targets, not substrates. However, their wide availability and the ease of their preparation in highly
enantioenriched form makes them attractive alkyl electrophiles to address challenges in asymmetric synthesis
and to identify new, previously untapped feedstocks for synthesis.
 Alkyl amines and alcohols can be prepared in high enantiopurity, making them ideal substrates for
stereospecific cross-coupling reactions. Via carbon–oxygen (C–O) and carbon–nitrogen (C–N) bond cleavage
of highly enantioenriched alcohol and amine derivatives, we will solve longstanding challenges in asymmetric
synthesis. These stereospecific cross-couplings will advance these alcohol and amine intermediates into
valuable, highly enantioenriched products, including those with traditionally challenging all-carbon quaternary
stereocenters.
 Primary alkyl amines are found in molecules ranging from simple starting materials to drugs and
biomolecules. Harnessing the ubiquitous amino (NH2) group, this research will develop chemistry to transform
NH2 groups into a host of other functional groups via cleavage of the C–N bond. The ability to transform a C–N
bond to a C–C (or C–X) bond offers powerful opportunities in late-stage functionalization of complex alkyl
amines, derivatization of biomolecules, and early-stage synthesis. This goal will be accomplished via nickel-
catalyzed cross couplings of redox-active Katritzky pyridinium salts, which are readily and selectively prepared
from primary alkyl amines.
 The successful development of this chemistry will enable efficient access to three-dimensional molecules
with potential bioactivity from widely available precursors. This research will also change the way chemists see
and use these functional groups. The ultimate goal of this research is to invent cross-coupling methods for
C(sp3)–X electrophiles that are as useful as those long-known for C(sp2)–X reagents for the discovery and
synthesis of new medicines. By opening a new door for the synthesis of novel, drug-like molecules, this
research will impact the discovery of new molecules with the potential to deepen our understanding of and
ability to treat human disease.

## Key facts

- **NIH application ID:** 9928065
- **Project number:** 5R35GM131816-02
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** Mary P Watson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,458
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928065

## Citation

> US National Institutes of Health, RePORTER application 9928065, Harnessing Alkyl Amines and Alkyl Alcohols in Cross-Coupling Reactions (5R35GM131816-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9928065. Licensed CC0.

---

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