Modular Diastereoselective Construction of Polysubstituted Cyclopentanes Enabled by Cobalt-Catalyzed Arylfluoroalkylation of Cyclopentenes

Abstract

A cobalt-catalyzed trans -selective arylfluoroalkylation of cyclopentenes has been developed. The reaction facilitates a modular diastereoselective synthesis of polysubstituted cyclopentanes by coupling inexpensive and readily available 3-cyclopentenecarboxylic acid derivatives with a wide range of arylzinc reagents and fluoroalkyl halides, including difluoroalkyl and perfluoroalkyl halides, in a one-pot reaction without lengthy synthesis. This cobalt-catalyzed process overcomes the limitations of nickel catalysis that undergoes the arylfluoroalkylation of 3-cyclopentenecarboxylic acid derivatives with low efficiency due to the competitive side reactions, featuring broad substrate scope, including complex molecules, high functional group tolerance, and synthetic convenience with low catalyst loading (cobalt catalyst as low as 0.5 mol %). The synthetic utility of this approach has also been demonstrated by the rapid modification of drug-like molecules and the diversified transformations of the resulting products, rendering the approach attractive for obtaining various fluorinated skeletons of medicinal interest. Experimental mechanistic studies reveal that a Co(I/II/III/I) redox catalytic cycle via a radical pathway is involved in the reaction, in which the cobalt(I) species is generated by the comproportionation of [Co II (L n )X 2 ] with in situ-generated Co(0).