Carbenoid-Mediated Homologation Tactics for Assembling (Fluorinated) Epoxides and Aziridines

In memory of Professor Hans Reich, a pioneer in organolithium chemistry.

Abstract

Homologation strategies provide highly versatile tools in organic synthesis for the introduction of a CH₂ group into a given carbon skeleton. The operation can result in diverse structural motifs by tuning of the reaction conditions and the nature of the homologating agent. In this Account, concisely contextualizing our work with lithium carbenoids (LiCH₂X, LiCHXY etc) for homologating carbon-centered electrophiles, we focus on the assembly of three-membered cycles featuring fluorinated substituents. Two illustrative case studies are considered: (1) the development and employment of fluorinated carbenoids en route to rare α-fluoroepoxides and aziridines, and (2) the installation of up to halomethylenic groups on trifluoroimidoylacetyl chlorides (TFAICs) for preparing CF₃-containing halo- and halomethylaziridines. Collectively, we demonstrate that the initial homologation event generated by the installation of the carbenoid, upon modulation of the conditions, serves as a tool for creating fluorinated building blocks in a single operation.

Key words

epoxides - aziridines - fluorine - homologation - carbenoids

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