# Harnessing Electron-Donor-Acceptor Complexes to Enable Photo-Induced Metal-Free Cross-Coupling Reactions

> **NIH NIH R35** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $354,039

## Abstract

Project Summary/Abstract
The abundance of C(sp3)–H bonds in organic molecules and building blocks, makes the direct functionalization
of these structures a very attractive and powerful tool for the synthesis and late-stage functionalization of
pharmaceuticals. Unfortunately, current methods to achieve these transformations use metal-catalysts and
reagents that do not meet requirements for sustainable development. Similarly, alkyl halides are among the
largest groups of commercially available building blocks used in organic chemistry, but bulky tertiary alkyl
halides cannot be easily used as alkylating agents because they cannot undergo SN2 processes. Therefore,
the development of strategies that are transition-metal-free and orthogonal to current approaches to activate
C–H and C–X bonds would be a significant contribution as it addresses an unmet need.
Recently, the application of electron-donor-acceptor (EDA) complexes has gained attention as a photo-induced
method to perform single electron transfers between otherwise unreactive reagents. Unfortunately, current
reactions that proceed via EDA complexes do not take advantage of the formed radicals to perform hydrogen-
atom-transfer (HAT) and halogen-atom-transfer (XAT) processes that could enable the use of the abundant
chemical feedstock mentioned above.
The research objectives of the proposed investigations promise to tackle the above-cited barriers to help
establish EDA complexes as a cutting-edge strategy for the photo-induced radical-activation of alkanes and
alkyl halides. Our conceptually innovative hypothesis is that sterically and electronically tuned aryl radicals
generated from EDA complexes can be used to achieve site-selective HAT and XAT processes. The resulting
alkyl radicals generated are then coupled to achieve enantio- and diastereoselective cross-couplings. This
work will use computational models to support, guide, and accelerate the design and discovery of EDA
complexes of arenes. These explorations will establish new platforms that enable enantio- and regioselective
cross-dehydrogenative couplings, and XAT mediated couplings that form challenging C(sp3)–C(sp3) bonds.

## Key facts

- **NIH application ID:** 10888301
- **Project number:** 5R35GM151227-02
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Sebastien Laulhe
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $354,039
- **Award type:** 5
- **Project period:** 2023-07-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888301

## Citation

> US National Institutes of Health, RePORTER application 10888301, Harnessing Electron-Donor-Acceptor Complexes to Enable Photo-Induced Metal-Free Cross-Coupling Reactions (5R35GM151227-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888301. Licensed CC0.

---

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