# New radical-based strategies for reaction discovery

> **NIH NIH R01** · CORNELL UNIVERSITY · 2024 · $357,535

## Abstract

Project Summary
The proposed research will uncover new radical-based methodologies that facilitate the synthesis of
complex bioactive compounds. Organic radicals are highly reactive species with unique
chemoselectivities that complement canonical two-electron chemistry. Recently, the emergence of new
reaction strategies that leverage single-electron redox events and harness radical intermediates for the
selective functionalization of organic molecules has provided chemists with useful tools for solving
contemporary synthetic problems. However, the highly reactive nature of many organic radicals has
made it difficult to impart catalyst-control over the regio- and stereoselectivity of these fleeting
intermediates, especially when complex reaction systems are concerned. In the past funding period, we
developed new catalytic strategies that leverage the unique redox features of low-valent Ti complexes to
achieve redox-neutral and net-reductive transformations, and through catalyst innovation, we
demonstrated that free radical-mediated reactions can be made highly enantioselective. These promising
results prompted us to continue to invent novel catalytic and reaction strategies that can effectively
harness radical intermediates and provide powerful tools for solving a range of longstanding synthetic
problems. In the new funding cycle, we will build on our previous success while moving our research into
important new areas of inquiry. In the proposed work, we aim to advance new approaches that employ
radical-based catalysts or reagents to address prominent challenges in organic synthesis. The
transformations targeted in each project area are either currently unknown or significantly limited in
reaction scope or selectivity. Some of the specific reactions that we aim to develop are: site-selective
oxidation of alcohols, enantioselective oxidation of amides and ethers, oxidative synthesis of stereogenic-
at-phosphorous(V) compounds, site-selective amination, halogenation, and desaturation of alkanes, and
deconstructive functionalization of alcohols. In-depth studies using canonical physical organic and
electroanalytical techniques will provide insights into the reaction mechanisms that will be used to guide
optimization. Ultimately, the realization of these proposed transformations will represent a significant
advance for the field of organic synthesis and support innovation in the synthesis of biomedically
important molecules.

## Key facts

- **NIH application ID:** 10980710
- **Project number:** 2R01GM134088-05A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Song Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $357,535
- **Award type:** 2
- **Project period:** 2020-04-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980710

## Citation

> US National Institutes of Health, RePORTER application 10980710, New radical-based strategies for reaction discovery (2R01GM134088-05A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10980710. Licensed CC0.

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