The geminal difluorocyclobutane core is a valuable structural element in medicinal chemistry. Strategies for gemdifluorocyclobutanes, especially the 2-substituted cases, are limiting and often suffer from harsh reaction conditions. Reported herein is a migratory gem-difluorination of aryl-substituted methylenecycloproanes (MCPs) for the synthesis of 2-arylsubstituted gemdifluorocyclobutanes. Commercially available Selectfluor (F-TEDA-BF 4 ) and Py•HF were used as the fluorine sources. The protocol proceeds via a Wagner−Meerwein rearrangement with mild reaction conditions, good functional group tolerance, and moderate to good yields. The product could be readily transformed to gem-difluorocyclobutane-containing carboxylic acid, amine, and alcohol, all of which are useful building blocks for biologically active molecule synthesis.Letter pubs.acs.org/OrgLett

A hypervalent iodine­(III)-mediated ring-contractive fluorination reaction of 2-alkylidenecyclobutanol derivatives is presented. The protocol allows the facile synthesis of β-monofluorinated cyclopropanecarbaldehydes via a fluorination/semipinacol rearrangement cascade using nucleophilic Py·HF as the fluorine source. For challenging electron-rich arene substrates, the installation of a protecting group on the free alcohol is pivotal for maintaining the reaction efficiency. The synthetic utility was demonstrated by the scalability of this reaction and further transformations of the products.

Reported herein is an in situ-generated hypervalent iodine-incorporating fluoroarylation of benzylidenecyclopropanes using commercially available HF•Py and aryl iodides as fluorine and aryl sources, respectively. The reaction proceeds via regioselective 1,2-fluoroiodination of a double bond followed by an iodonio-[3,3]-rearrangement of the formed cyclopropyl-I (III) species. The protocol offers facile access to valuable monofluorinated 1,1-bisbenzyl-alkenes with mild reaction conditions and moderate to good yields. The synthetic utility of the products was demonstrated by further transformations. Preliminary mechanistic studies were conducted.

A photocatalytic Z to E isomerization of monofluorostilbenes in the presence of visible light (blue LEDs) has been developed. The transformation, which proceeds through a selective energy transfer pathway with Ir(III) complex, offers facile access to thermodynamically less stable E-monofluoroalkenes with synthetically useful efficiency (up to 96% yield, up to 91∶ 9 E∶Z). Mild reaction conditions, good functional groups tolerance, and broad substrate scope were observed. Furthermore, the synthetic utility of this method is demonstrated by the rapid synthesis of monofluorinated cis-DMU-212 analogue E-30.

Described herein is a hypervalent iodine(III)-mediated ring-expansive difluorination of alkynylcyclopropanes using commercially available Olah’s reagent (HF∙Py) as the fluorine source. The approach allows the facile synthesis of difluorinated alkylidenecyclobutanes with...