# Transition Metal Catalyzed Reductive Carbene Transfer Reactions

> **NIH NIH R35** · PURDUE UNIVERSITY · 2020 · $370,571

## Abstract

Abstract
 Carbenes are valuable reactive intermediates in organic synthesis capable of selectively targeting non-
polar π-systems and element–hydrogen bonds in the presence of common polar functional groups. The advent
of transition metal catalysis has greatly expanded the utility of carbene transfer reactions, tempering the
reactivity of free carbenes and enabling high levels of chemo-, regio-, and stereoselectivity to be achieved
under catalyst control. Current methods for catalytic carbene transfer have predominately relied on the
extrusion of N2 from diazoalkanes as a central strategy for generating metal carbenoid intermediates. Despite
the synthetic utility of these approaches, many state-of-the-art methods are restricted to a relatively narrow
scope of diazoacetates, and their derivatives, due to the requirement for stabilizing electron-withdrawing
substituents. The overarching goal of this proposed research program is to design a new class of reductive
carbene transfer reactions that use readily available and indefinitely stable 1,1-dichloroalkanes as carbene
precursors. The primary impact of this work will be to enable catalytic transfer reactions of non-stabilized
carbene equivalents, providing direct access to novel synthetic building blocks and facilitating challenging bond
constructions.
 Our central hypothesis is that the elementary steps of transition metal-catalyzed cross-coupling reactions
can be re-purposed to enable carbene-type reactivity. Specifically, the oxidative addition of a 1,1-dihaloalkane
at a low-valent nickel catalyst is proposed to generate catalyst-bound carbenoid equivalents that can be used
in broad range of transformations. Under this general catalytic manifold, we will pursue reductive
cyclopropanations, methylene cyclopropanations, multicomponent cycloadditions, cyclooligomerization
reactions, C(sp2)–H bonds insertion reactions, and heteroatom–H insertion reactions. In tandem with the
development of synthetic methods, mechanistic studies will be conducted to highlight the unique properties of
nickel-bound carbenoids. Collectively, the methods described in this proposal will enable the synthesis of novel
biologically active compounds by providing rapid access to privileged substructures.

## Key facts

- **NIH application ID:** 9978829
- **Project number:** 5R35GM124791-04
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** Christopher Uyeda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,571
- **Award type:** 5
- **Project period:** 2017-08-08 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978829

## Citation

> US National Institutes of Health, RePORTER application 9978829, Transition Metal Catalyzed Reductive Carbene Transfer Reactions (5R35GM124791-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9978829. Licensed CC0.

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