# Ligand-promoted Enantioselective C-H Activation Reactions

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 2023 · $109,546

## Abstract

Project Summary
By harnessing abundant prochiral C(sp3)–H bonds as entry points for the stereoselective installation of
complex functionality, enantioselective C(sp3)–H functionalization represents a potentially transformative
strategy in synthesis. Although enantioselective transition metal-catalyzed C(sp3)–H activation reactions
have been reported, many require bespoke directing groups – a serious synthetic limitation. The use of
functional groups native to common organic substrates (amides, acids, alcohols, ethers, amines, and
esters) to recruit the catalyst for C–H metalation is ideal, but many native functionalities are either weakly
coordinating or have otherwise undesirable binding capabilities with the catalyst. This proposal addresses
these challenges through two distinct design strategies, which aim to enable both reactivity and
enantioselectivity for native functionality-directed C(sp3)–H activation reactions. In particular, our research
strategy aims to achieve the enantioselective C–H activation of carboxylic acid, amide, alcohol, ester,
aldehyde, ketone, and amine-containing substrates with diverse reacting partners through (A) the design
of chiral bidentate L,X-type scaffolds bearing N-acetyl (NHAc) or pyridone motifs to accelerate C–H
cleavage, and (B) the design of chiral transient directing groups (TDGs). The advances from this proposal
can fundamentally impact both how chiral molecules are constructed and diversified in pharmaceutical and
synthesis contexts. Moreover, these new catalytic platforms will be immediately applied in a pharmaceutical
context through industrial (with BMS), and academic collaborations (with Prof. Benjamin Cravatt), where
the synthesis of novel chiral β-lactones and lactams through enantioselective C–H activation will expedite
the discovery of novel enzyme inhibitors in an anticancer context.

## Key facts

- **NIH application ID:** 10799446
- **Project number:** 3R01GM084019-15S1
- **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:** $109,546
- **Award type:** 3
- **Project period:** 2008-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10799446

## Citation

> US National Institutes of Health, RePORTER application 10799446, Ligand-promoted Enantioselective C-H Activation Reactions (3R01GM084019-15S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10799446. Licensed CC0.

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