An efficient approach to gem-difluorocyclopropylstannanes via highly regio- and stereoselective hydrostannylation of gem-difluorocyclopropenes and their unique ring-opening reaction to afford β-fluoroallylic alcohols

Abstract

Treatment of various gem-difluorocyclopropenes with 1.2 equiv. of n-Bu3SnH in the presence of 20 mol% of Et3B at 80 °C for 4 h led to the quantitative formation of the hydrostannylated products in a highly regio- and trans-selective manner. Additionally, the prepared trans-gem-difluorocyclopropylstannanes were treated with 1.5 equiv. of MeLi in THF at -78 °C for 5 min, followed by quenching the reaction with various agents, such as H2O, alcohols, carboxylic acids, and tosylamide, to give the corresponding β-fluoroallylic alcohols, ethers, esters, and amides respectively with exclusive Z selectivity in acceptable yields.

Regio- and Diastereoselective Hydrophosphination and Hydroamidation of gem-Difluorocyclopropenes

“…Hydro- or carbo-functionalization of gem -difluorocyclopropenes is an alternative route of preparation, in which diverse valuable functional groups would be introduced to gem -difluorocyclopropenes in a regio- and diastereoselective manner. In this context, Konno and co-workers reported an Et 3 B-catalyzed hydrostannylation of gem -difluorocyclopropenes to access tinned gem -difluorocyclopropanes; Cao’s group elaborated a highly regio- and diastereoselective copper-catalyzed hydroborylation and hydrosilylation of difluorocyclopropenes with B 2 pin 2 and PhMe 2 Si-Bpin . Meanwhile, highly functionalized 5-fluoropyridazine and 4-fluoropyridine derivatives were effectively constructed through a [3 + 2]­[2 + 1] cycloaddition sequence between gem -difluorocyclopropenes and acceptor carbenes or methylene isonitriles (Scheme a) .…”

Practical conversion of gem-difluorocyclopropenes for the chemodivergent assembly of fluorinated heterocyclic frameworks

“…of the C–C double bond in gem -difluorocyclopropenes were also realized and represented an efficient strategy for the construction of attracting gem -difluorocyclopropane motifs. 9 As a comparison, by defining gem -difluorocyclopropene as a type of versatile dipolarophile, copper- or photo-mediated cycloaddition reactions with different dipoles proceeded smoothly to deliver fluorinated heterocycles. 10 These conversions demonstrated the profound chemical diversity of gem -difluorocyclopropene skeletons and provided adequate evidence to support further development of novel, green and practical protocols with this substrate for chemodivergent synthesis of fluorinated heterocyclic frameworks.…”

Enantioselective Functionalization of Difluorocyclopropenes Catalyzed by Chiral Copper Complexes: Proposal for Chiral gem-Dimethyl and tert-Butyl Analogues

“…Recently, radical hydrostannylation reaction of difluorocyclopropene was reported (Scheme 1, eq 1), but subsequent treatment of the tin intermediates with methyllithium led only to cyclopropane ring-opening products. 5 Obviously, development of a transition-metal-catalyzed hydrometalation reaction of difluorocyclopropenes is a formidable endeavor, particularly in an enantioselective manner. Herein, we report the highly regio-and stereoselective coppercatalyzed functionalization of difluorocyclopropenes under mild reaction conditions even at ambient temperature (Scheme 1, eq 2).…”

“…However, synthetic transformation of difluorocyclopropenes via hydro- or carbo-functionalization is quite limited due to their instability under various reaction conditions. Recently, radical hydrostannylation reaction of difluorocyclopropene was reported (Scheme , eq 1), but subsequent treatment of the tin intermediates with methyllithium led only to cyclopropane ring-opening products . Obviously, development of a transition-metal-catalyzed hydrometalation reaction of difluorocyclopropenes is a formidable endeavor, particularly in an enantioselective manner.…”