Nickel-Catalyzed Cross-Electrophile Coupling of Alkyl Fluorides: Stereospecific Synthesis of Vinylcyclopropanes

Abstract

The stereospecific reductive cross-electrophile coupling reaction of 2-vinyl-4-halotetrahydropyrans for vinylcyclopropane synthesis is reported. The nickel-catalyzed reaction occurs with both alkyl fluorides and alkyl chlorides. To the best of our knowledge, this is the first reported cross-electrophile coupling reaction of an alkyl fluoride. Ring contraction proceeds with high stereospecificity, providing selective synthesis of either diastereomer of di- and trisubstituted cyclopropanes. The utility of this methodology is demonstrated by several synthetic applications including the synthesis of the natural product dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific ring contractions, providing access to synthetically useful hydroxymethyl cyclopropanes.

Stereoselective cis-Vinylcyclopropanation via a Gold(I)-Catalyzed Retro-Buchner Reaction under Mild Conditions

“…18 In general, diastereopure vinylcyclopropanes are accessed in a stepwise manner through derivatization of functionalized cyclopropane building blocks, by either Wittig olefination 19 or metal-catalyzed cross-couplings. 20,21 …”

Nickel-Catalyzed Cross-Electrophile Coupling of the Difluoromethyl Group for Fluorinated Cyclopropane Synthesis

“…in a related XEC reaction for fluorinated cyclopropane synthesis. 8 The notion of engaging the carbon-fluorine bond of a difluoromethyl group in a XEC reaction presents a notable challenge: the strength of the C-F bond increases with each additional fluorine atom attached to the central carbon atom due to increased electrostatic forces. 9 This work describes a new approach for fluorinated cyclopropane synthesis, wherein the photocatalytic difluoromethylation of olefins is paired with a nickel-catalyzed intramolecular XEC reaction between benzylic ethers and difluoromethyl groups.…”

Nickel-Catalyzed Favorskii-Type Rearrangement of Cyclobutanone Oxime Esters to Cyclopropanecarbonitriles

“…Strategies for cyclopropane formation under nickel catalysis are rare and can be divided into two categories (Scheme 1b): nickel-catalyzed Simmons-Smith-type cyclopropanation and nickel-catalyzed intramolecular reductive cross coupling. 11,12 Here, we report a new strategy to prepare cyclopropane nitriles by using cyclobutanone oxime esters as starting materials.…”