Mild and Copper‐Free Stereoselective Cyanation of gem‐Difluoroalkenes by Using Benzyl Nitrile as a Cyanating Reagent

Abstract

A novel copper-free highly stereoselective cyanation of gem-difluoroalkenes by using benzyl nitrile as a cyanating reagent with the assistance of tBuOLi under air atmosphere at room temperature was developed. A variety of versatile fluorinated alkenyl nitriles were obtained. The proposed mechanism involved the C-H bond oxidation, C-CN bond cleavage, and then nucleophilic vinylic substitution (SN V).

Bond energy enabled amine distinguishing strategy: chemo-, regioselective 1,3-diamination of (trifluoromethyl)alkenes with different amines by two C(sp3)–F bond cleavages

“…The significantly reduced electronic repulsion between the aryl group and fluorine atom in D1 conformation should be more favored than that of D2. 26 Thus, β-fluorine elimination from the favored D1 conformation of β-fluorocarbanion intermediate D generates the monofluoroalkenylated 1,3-diamination product 4 in the major Z-isomer. The interaction between the alkali-metal ion and the fluorine atom might favor the leaving of fluoride in the ipso-selective defluorinative amination step.…”

Rhodium‐Catalyzed Defluorinative Vinylation of gem‐Difluoroalkenes for the Synthesis of 2‐Fluoro‐1,3‐dienes

“…In this regard, gem ‐difluoroalkene represents a useful reaction component as that is easily available from aldehydes, ketones, alkyl halides, trifluoromethyl allyl/propargyl/alkenyl carbonates and diazo compounds. Such fluorinated alkene has been employed as a versatile building block, with which a large variety of mono‐fluoroalkenes featuring synthetically important functionalities, including aryl, alkyl, alkynyl, cyano, trifluoromethyl, as well as heteroatoms, have been successfully prepared through transition‐metal‐catalyzed or radical‐engaged functionalization of the classically considered inert C—F bond. Among the established protocols, C—H activation coupled C—F bond functionalization is of particular interest because of the outstanding efficiency and broad substrate scope.…”

Copper‐Catalyzed Stereoselective Defluorinative Borylation and Silylation of gem‐Difluoroalkenes

“…As a consequence, the nucleophilic defluorinative substitution reactions following an addition‐elimination mechanism have been extensively explored by employing diverse oxygen, nitrogen, sulfur or even carbon‐centered, nucleophiles. On the other hand, the transition metal‐catalyzed cross‐couplings of gem ‐difluoroalkenes with organometallic reagents provided a valuable strategy to access monofluoroalkenes .…”