# Ligand-Promoted Enantioselective C-H Activation Reaction

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $597,333

## Abstract

Project Summary
 Desymmetrizing activation of prochiral C–H bonds via metal insertion has emerged as a potentially
transformative approach for the rapid and divergent synthesis of chiral compounds. However, a significant
challenge prohibiting the broad utility of this approach is the poor reactivity of native substrates in the absence
of externally-appended directing groups. This proposal directly addresses this challenge by developing two
approaches to achieve the enantioselective C–H activation of a range of native substrates commonly found in
organic synthesis and drug discovery—carboxylic acids, ketones, aldehydes and amines: (A) Development of
chiral bidentate L,X-type ligands containing N-acetyl or pyridone motifs to accelerate C–H cleavage; (B)
Development of chiral transient directing groups (TDGs) to enable enantioselective C–H activation of ketones,
aldehydes and amines. Following initial discoveries of chiral ligands and TDGs, we will then develop various
catalytic cycles to enable the enantioselective C–H activation of diverse native substrates, forming a range of
carbon–carbon and carbon–heteroatom bonds asymmetrically. These novel reactions will provide a versatile
platform for the construction of -, -, and -stereocenters. These technologies will be applied to drug
discovery in collaboration with the pharmaceutical industry and academic laboratories. Specifically, the one-
step access to the atypical chiral -lactones and lactams via enantioselective C–H activation will be applied to
the discovery of covalent inhibitors for serine hydrolases and cysteine-dependent proteins using activity-based
protein profiling.

## Key facts

- **NIH application ID:** 10651648
- **Project number:** 5R01GM084019-16
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Jin-Quan Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $597,333
- **Award type:** 5
- **Project period:** 2008-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10651648

## Citation

> US National Institutes of Health, RePORTER application 10651648, Ligand-Promoted Enantioselective C-H Activation Reaction (5R01GM084019-16). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10651648. Licensed CC0.

---

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