# Ligand-promoted Enantioselective C-H Activation Reactions

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $619,200

## Abstract

Project Summary
 While metal insertion into, and subsequent functionalization of, sp3 C−H bonds has the potential to afford
transformative tools in synthesis, the impact of this approach on asymmetric catalysis has been moderate due
to a number of unanswered challenges encountered in the development of asymmetric version of these
reactions. This proposal centers on the development of two approaches for enantioselective C–H activation
reactions of broadly useful substrates: (A) the design of bisdentate chiral ligands and (B) catalytic chiral
directing groups. We will develop enantioselective C–H activation reactions of -methyl C–H bonds and
methylene C–H bonds of carboxylic acids and carboxylate derived substrates, as well as -C–H bonds of
amines and amine derived substrates. These reactions will provide novel and versatile methodologies for
constructing -, -, and -chiral centers in asymmetric synthesis. The use of abundant and common
substrates, as well as the diversity of the transformations will render palladium-catalyzed enantioselective C–H
functionalization broadly useful for the synthesis of bioactive chiral molecules. Specifically, desymmetrization of
isobutyric and pivalic acids via enantioselective C–H activation will be applied to the generation of a library of
novel serine hydrolase inhibitors that can be evaluated by activity-based protein profiling to identify new drug
leads for diabetes, cognitive dementia and bacterial infection.

## Key facts

- **NIH application ID:** 9990778
- **Project number:** 5R01GM084019-13
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Jin-Quan Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $619,200
- **Award type:** 5
- **Project period:** 2008-08-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990778

## Citation

> US National Institutes of Health, RePORTER application 9990778, Ligand-promoted Enantioselective C-H Activation Reactions (5R01GM084019-13). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9990778. Licensed CC0.

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