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

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, LiCHXYetc) 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 carbenoidsen routeto rare alpha-fluoroepoxides and aziridines, and (2) the installation ofup tohalomethylenic groups on trifluoroimidoylacetyl chlorides (TFA-ICs) 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.

Automated summary

Homologation strategies provide versatile tools for introducing CH2 group into carbon skeletons in organic synthesis, resulting in diverse structural motifs through tuning of reaction conditions and homologating agent. By utilizing methods such as fluorinated carbenoids, three-membered cycles with fluorinated substituents can be efficiently assembled.