journal article·2022-04Open access

Reactivity of triplet diradical intermediates in aqueous media for transition-metal-free Csp2–H alkylation

Prithwish Ghosh, Youjung Byun, Na Yeon Kwon, Ju Young Kang, Neeraj Kumar Mishra, Jung Su Park, In Su Kim

Cell Reports Physical Science· Volume 3· Issue 4

Abstract

Alkyl pyridinium salts have been used in dipolar cycloaddition reactions with π-unsaturated compounds and in reductive single-electron transfer reactions as convenient radical precursors. Here, we report a distinct reaction pathway involving triplet diradical intermediates in the coupling reaction between alkyl pyridinium ylides and electrophilic N-heterocyclic molecules. We demonstrate that alkyl pyridinium ylides generated from alkyl pyridinium salts under basic aqueous conditions can undergo addition into iminoamido N-heterocycles, generating triplet diradical intermediates that can lead to C–H alkylated products. The proposed reaction mechanism is supported by electron paramagnetic resonance and radical scavenging experiments. Notably, a wide substrate scope and excellent level of functional group tolerance are attained under cost-effective and straightforward conditions, which reveal the amenability of this protocol in the pharmaceutical and chemical industries.
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Research context

OpenAlex topics: Catalytic C–H Functionalization Methods · Synthesis and Biological Evaluation · Cyclopropane Reaction Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

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