Copper-Catalyzed Ring-Opening Defluoroborylation of gem-Difluorinated Cyclobutenes: A General Route to Bifunctional 1,3-Dienes and Their Applications

Abstract

The exploration of the reactivity of gem-difluorinated small-size rings has continuously drawn attention in recent years but is limited to three-membered carbocycles. Herein we report a copper-catalyzed reaction of gem-fluorinated cyclobutenes with bis­(pinacolato)­diboron (B2pin2). A sequence of defluoroborylation and a ring-opening process produces B,F-bifunctional 1,3-dienes in a stereoselective manner. The transformation together with the efficient downstream coupling of the boronate and the fluoride moieties collectively constitutes a modular route to highly functionalized and stereocontrolled 1,3-dienes.

Lewis Acid-Catalyzed Ring-Opening Cross-Coupling Reaction of gem-Difluorinated Cyclopropanes Enabled by C–F Bond Activation

“…Considering that gem -difluorinated cyclopropanes contain two C(sp 3 )–F bonds, we envisaged that a fluorophilic Lewis acid might have the potential to activate this special C(sp 3 )–F bond, therefore providing an alternative strategy other than transition-metal catalysis for the cross-coupling of gem -difluorinated cyclopropanes. Based on this concept and our research interests in small-ring transformations, , we herein disclose a Lewis acid-catalyzed cross-coupling reaction of mono- or disubstituted gem -difluorinated cyclopropanes with electron-rich arenes and allylsilanes. A key feature of the strategy is that a sequence of C(sp 3 )–F bond activation and C–C bond cleavage might occur to form a putative fluoroallylic cation intermediate rather than C–C activation first followed by C–F bond cleavage to give a fluoroallyl metal species, which occurs in transition-metal catalysis.…”

Diversified Synthesis of Chiral Fluorinated Cyclobutane Derivatives Enabled by Regio‐ and Enantioselective Hydroboration

“…Instead of direct hydroboration, the group of Tortosa [6] and Hall [7] alternatively developed the use of diboron reagent (bis(pinacolato)diboron, B 2 Pin 2 ) to realize the formal hydroboration of some cyclobutenes under copper catalysis, [8] providing an elegant approach to chiral boryl cyclobutanes [9] (Scheme 1a). We previously applied the Cu/B 2 Pin 2 system in the reaction of gem ‐difluorinated cyclobutenes, expecting to obtain fluorinated cyclobutane derivatives via formal hydroboration; however, the reaction undergoes β‐boryl addition/fluorine elimination followed by thermal ring‐opening process, resulting in the production of B,F‐bifunctional 1,3‐dienes (Scheme 1b) [10] …”

“…We previously applied the Cu/B 2 Pin 2 system in the reaction of gemdifluorinated cyclobutenes, expecting to obtain fluorinated cyclobutane derivatives via formal hydroboration; however, the reaction undergoes β-boryl addition/fluorine elimination followed by thermal ring-opening process, resulting in the production of B,F-bifunctional 1,3-dienes (Scheme 1b). [10] This result indicates that there exist certain challenges for the asymmetric hydroboration of gem-difluorinated cyclobutenes that must be taken into consideration. First, how to control the ring-opening tendency of the fourmembered ring due to the inherent ring strain; [11,12] second, how to control the potential elimination of the fluorine atoms through either B,F-elimination of the α-boryl prod-ucts or H,F-elimination of the β-boryl products; [13,14] finally, the precise control of the regio-, diastereo-and enantioselectivity of the reaction is a nontrivial task.…”

Nickel‐Catalyzed Tunable Enantioconvergence and Kinetic Resolution in the Coupling of Tertiary Cyclobutenols with Arylboroxines

“…[3b, 17] In addition, regio-and enantioselectivity are also nontrivial issues for the reaction with a strained allylic partner. Following our research interests in small-ring transformations [18] and quaternary-stereocenter constructions, [19] we herein disclose that a catalytic system consisting of a nickel(0) complex and a modified SPINOLphosphoramidite ligand can successfully realize the asymmetric allylic coupling reaction between tertiary cyclobutenols and arylboroxines. This transformation takes advantage of nickel catalysis for C-O bond activation [8e,f] and allows the direct use of OH as the leaving group without additional activation, [20] enabling the precise installation of all-carbon quaternary stereocenters at the α-position with excellent enantioselectivity.…”