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Nickel-Catalyzed Alkyl–Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes

Amberly B. Sanford, Taylor A. Thane, Tristan M. McGinnis, Pan‐Pan Chen, Xin Hong, Elizabeth R. Jarvo

2020Journal of the American Chemical Society85 citationsDOIOpen Access PDF

Abstract

-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.

Topics & Concepts

ChemistryAlkylElectrophileNickelCatalysisCoupling reactionCoupling (piping)Beta-Hydride eliminationOrganic chemistryMedicinal chemistryPolymer chemistryMetallurgyMaterials scienceCyclopropane Reaction MechanismsCatalytic Cross-Coupling ReactionsCatalytic C–H Functionalization Methods