# Transition Metal Catalyzed Reductive Carbene Transfer Reactions

> **NIH NIH R35** · PURDUE UNIVERSITY · 2024 · $69,061

## Abstract

Project Summary/Abstract
 Carbenes are versatile reactive intermediates capable of engaging in cycloaddition, bond insertion,
rearrangement, and coupling reactions. Previous efforts to develop catalytic variants of carbene transfer
reactions have largely focused on the use of diazoalkanes. The primary limitation of this approach is that
diazoalkanes generally must be stabilized with electron-withdrawing or aryl groups in order to avoid the
spontaneous, exothermic elimination of dinitrogen gas. The overarching goal of this program is to study
transition metal catalyzed reductive carbene transfer reactions that use readily available gem-dihalo reagents
as precursors to non-stabilized carbenes. Catalytic turnover can be achieved using chemical reductants, such
as metal powders. Alternatively, the use of photoredox or electrocatalytic reduction makes these reactions
compatible with emerging flow synthesis platforms.
 A broad scope of catalytic cycloaddition reactions will be developed. A particular focus will be on
generating odd-membered rings, which are challenging to access by conventional thermal pericyclic
processes. For example, transition metal catalysis will allow current limitations of the Simmons–Smith reaction
to be addressed, such as the enantioselective synthesis of dimethyl-, spiro-, and methylenecyclopropanes.
Asymmetric [4 + 1]-cycloadditions of vinylidenes and 1,3-dienes will generate complex cyclopentene
derivatives. Finally, three-component [n + m + 1]-cycloadditions will be developed for the synthesis of five- and
seven-membered carbocycles and heterocycles. Some of these reactions will use dinuclear metal catalysts,
which provide a unique active site environment to mediate carbene and vinylidene transfer reactions.
 Transition metal-catalyzed additions of vinylidenes to alkenes can also be diverted to non-cycloaddition
pathways by intercepting metalacyclic intermediates prior to ring closure. Reaction design is based on
promoting β-X elimination or transmetalation reactions of these metalacycles. Based on this concept, novel
carbon–carbon coupling reactions will be developed for the synthesis of chiral alcohol and amine products.
 The catalysis concepts developed in this project will impact human health by providing access to complex
C(sp3)-rich frameworks that can be incorporated into biological probes and therapeutics.

## Key facts

- **NIH application ID:** 11137167
- **Project number:** 3R35GM124791-08S1
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Christopher Uyeda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $69,061
- **Award type:** 3
- **Project period:** 2017-08-08 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11137167

## Citation

> US National Institutes of Health, RePORTER application 11137167, Transition Metal Catalyzed Reductive Carbene Transfer Reactions (3R35GM124791-08S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11137167. Licensed CC0.

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