# Radical redox catalysis by Ti complexes

> **NIH NIH R01** · CORNELL UNIVERSITY · 2021 · $309,107

## Abstract

Project Summary
This proposal focuses on uncovering new radical-based catalytic methodologies that facilitate the
synthesis of bioactive compounds. Organic radicals are highly reactive species with unique
chemoselectivities that complement canonical two-electron chemistry. Recently, the emergence of new
catalytic 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 selectivity of these fleeting intermediates, especially
when complex reaction systems are concerned. In particular, catalytic stereoselective reactions
involving free radical intermediates remain limited, and the discovery of such processes is highly
desirable. To provide new radical-based platforms for reaction discovery and synthetic innovation, we
recently developed a novel catalytic approach that exploits the unique redox features of Ti complexes.
Specifically, we advanced a new strategy—radical redox-relay catalysis—for the development of redox-
neutral reactions that combines single-electron oxidation and reduction events in the same catalytic
cycle. This strategy was successfully implemented in the stereoselective Ti-catalyzed cycloaddition of
N-acylaziridines or cyclopropyl ketones with alkenes as well as Ti/Co co-catalyzed rearrangement of
epoxides to allylic alcohols. On the strength of these promising results, we anticipate that such radical
catalysis strategies will ultimately emerge as powerful tools for solving a wide range of long-standing
synthetic problems. Each project in this proposal applies our general strategy of Ti redox catalysis to
address a prominent challenge in organic synthesis. Specifically, we aim to develop reactions that
achieve enantioselective [3+2] cycloaddition, enantioselective epoxide isomerization, synthesis of
skipped enones, and isomerization of aziridines to allylic amines. These transformations are either
currently unknown or have significant limitations in reaction scope, efficiency, or selectivity. We will also
carry out in-depth studies using canonical physical organic and electrochemical techniques to gain
insights into the mechanisms of these reactions. The development and mechanistic understanding of
these proposed transformations will represent significant advances for the field of organic synthesis.

## Key facts

- **NIH application ID:** 10127671
- **Project number:** 5R01GM134088-02
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Song Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $309,107
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10127671

## Citation

> US National Institutes of Health, RePORTER application 10127671, Radical redox catalysis by Ti complexes (5R01GM134088-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10127671. Licensed CC0.

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