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

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 (S_NV).     

Stereoselective Synthesis of Z Fluoroalkenes through Copper‐Catalyzed Hydrodefluorination of gem‐Difluoroalkenes with Water

A copper catalytic system was established for the stereoselective hydrodefluorination of gem‐difluoroalkenes through C−F activation to synthesize various Z fluoroalkenes. H₂O is used as the hydrogen source for the fluorine acceptor moiety. This mild catalytic system shows good‐functional group compatibility, accepting a range of carbonyls as precursors to the gem‐difluoroalkenes, including aliphatic, aromatic, and α,β‐unsaturated aldehydes and even ketones. It serves as a powerful synthetic method for the late‐stage modification of complex compounds.     

Metal‐Free Direct C−H Cyanation of Alkenes

A metal‐free and direct alkene C?H cyanation is described. Directing groups are not required and the mechanism involves electrophilic activation of the alkene by a cyano iodine(III) species generated in situ from a [bis(trifluoroacetoxy)iodo]arene and trimethylsilyl cyanide as the cyanide source. This C?H functionalization can be conducted on gram scale, and for noncyclic 1,1‐ and 1,2‐disubstuted alkenes high stereoselectivity is achieved, thus rendering the method highly valuable.     

Palladium‐Catalyzed Defluorinative Coupling of 1‐Aryl‐2,2‐Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes

The palladium‐catalyzed defluorinative coupling of 1‐aryl‐2,2‐difluoroalkenes with boronic acids is described. Broad functional‐group tolerance arises from a redox‐neutral process by a palladium(II) active species which is proposed to undergo a β‐fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, and it is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method's unique combination of reactivity and functional‐group tolerance, a Gleevec® analogue, using a monofluorostilbene as an amide isostere, was synthesized.     

Regio‐ and Stereospecific 1,3‐Allyl Group Transfer Triggered by a Copper‐Catalyzed Borylation/ortho‐Cyanation Cascade

A copper‐catalyzed borylation/ortho‐cyanation/allyl group transfer cascade was developed. Initiated by an unconventional copper‐catalyzed electrophilic dearomatization, this process features regio‐ and stereospecific 1,3‐transposition of the allyl fragment enabled by an aromatization‐driven Cope rearrangement. This method provides an effective means for the construction of adjacent tertiary and quaternary stereocenters with excellent diastereocontrol.     

Copper‐Catalyzed Intermolecular Trifluoromethylazidation of Alkenes: Convenient Access to CF3‐Containing Alkyl Azides

A novel copper‐catalyzed intermolecular trifluoromethylazidation of alkenes has been developed under mild reaction conditions. A variety of CF₃‐containing organoazides were directly synthesized from a wide range of olefins, including activated and unactivated alkenes, and the resulting products can be easily transformed into the corresponding CF₃‐containing amine derivatives.     

Amidyl Radicals by Oxidation of α‐Amido‐oxy Acids: Transition‐Metal‐Free Amidofluorination of Unactivated Alkenes

A three‐component transition‐metal‐free amidofluorination of unactivated alkenes and styrenes is presented. α‐Amido‐oxy acids are introduced as efficient and easily accessible amidyl radical precursors that are oxidized by a photoexcited organic sensitizer (Mes‐Acr‐Me) to the corresponding carboxyl radical. Sequential CO₂ and aldehyde/ketone fragmentation leads to an N‐centered radical that adds to an alkene. Commercial Selectfluor is used to trap the adduct radical through fluorine‐atom transfer. The transformation features by high functional‐group tolerance, broad substrate scope, and practical mild conditions. Mechanistic studies support the radical nature of the cascade.     

Mild Silver‐Mediated Geminal Difluorination of Styrenes Using an Air‐ and Moisture‐Stable Fluoroiodane Reagent

An air‐ and moisture‐stable fluoroiodane in the presence of AgBF₄ is suitable for selective geminal difluorination of styrenes under mild reaction conditions. One of the C? F bonds is formed by transfer of electrophilic fluorine from the hypervalent iodine reagent, while the other one arises from the tetrafluoroborate counterion of silver. Deuterium‐isotope‐labelling experiments and rearrangement of methyl styrene substrates suggest that the reaction proceeds through a phenonium ion intermediate.     

Defluorinative C(sp3)−P Bond Construction for the Synthesis of Phosphorylation gem‐Difluoroalkenes under Catalyst‐ and Oxidant‐Free Conditions

Defluorinative C(sp³)?P bond formation of α‐trifluoromethyl alkenes with phosphine oxides or phosphonates have been achieved under catalyst‐ and oxidant‐free conditions, giving phosphorylation gem‐difluoroalkenes as products. α‐Trifluoromethyl alkenes bearing various of aryl substituents such as halogen, cyano, ester and heterocyclic groups are available in this transformation. The results of control experiments demonstrated that the mechanism of dehydrogenative/defluorinative cross‐coupling reactions was not a radical route, but might be an S_N2′ process involving phosphine oxide anion.     

Water‐Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4‐Oxadiazoles

Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water‐assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4–5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five‐ and six‐membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4‐oxadiazole derivatives having a unique hybrid isoxazoline‐oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly‐like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.     

Regio‐ and Stereoselective Thianthrenation of Olefins To Access Versatile Alkenyl Electrophiles

Herein, we report a regioselective alkenyl electrophile synthesis from unactivated olefins that is based on a direct and regioselective C?H thianthrenation reaction. The selectivity is proposed to arise from an unusual inverse‐electron‐demand hetero‐Diels–Alder reaction. The alkenyl sulfonium salts can serve as electrophiles in palladium‐ and ruthenium‐catalyzed cross‐coupling reactions to make alkenyl C?C, C?Cl, C?Br, and C?SCF₃ bonds with stereoretention.