Photoredox‐Catalyzed Stereoselective Conversion of Alkynes into Tetrasubstituted Trifluoromethylated Alkenes

A regio‐ and stereoselective synthesis of trifluoromethylated alkenes bearing four different substituents has been developed. Stereocontrolled sulfonyloxytrifluoromethylation of unsymmetric internal alkynes with an electrophilic CF₃ reagent, namely the triflate salt of the Yagupol’skii–Umemoto reagent, in the presence of an Ir photoredox catalyst under visible‐light irradiation afforded trifluoromethylalkenyl triflates with well‐predictable stereochemistry resulting from anti addition of the trifluoromethyl and triflate groups. Subsequent palladium‐catalyzed cross‐couplings led to tetrasubstituted trifluoromethylated alkenes in a highly stereoselective manner. The present method is the first example of a facile one‐pot synthesis of tetrasubstituted trifluoromethylated alkenes from simple alkynes.     

Visible‐Light‐Induced Hydrodifluoromethylation of Alkenes with a Bromodifluoromethylphosphonium Bromide

Bromodifluoromethylphosphonium bromide was solely used as the precursor of difluorocarbene. Herein, an unprecedented visible‐light‐induced hydrodifluoromethylation of alkenes with bromodifluoromethylphosphonium bromide using H₂O and THF as hydrogen sources for the synthesis of difluoromethylated alkanes is described. This difluoromethylation is characterized by mild reaction conditions, ready availability of reagents, and excellent functional‐group tolerance.     

Efficient Cu‐catalyzed Atom Transfer Radical Addition Reactions of Fluoroalkylsulfonyl Chlorides with Electron‐deficient Alkenes Induced by Visible Light

Fluoroalkylsulfonyl chlorides, R_fSO₂Cl, in which R_f=CF₃, C₄F₉, CF₂H, CH₂F, and CH₂CF₃, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron‐deficient, unsaturated carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α‐chloro‐β‐fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α‐chloro substituent is shown to lead to further diverse functionalization of the products.     

Phosphine‐Catalyzed [3+2] Cycloaddition Reactions of Azomethine Imines with Electron‐Deficient Alkenes: A Facile Access to Dinitrogen‐Fused Heterocycles

An efficient method for the phosphine‐catalyzed [3+2] cycloaddition reaction of azomethine imines with diphenylsulfonyl alkenes to give dinitrogen‐fused bi‐ or tricyclic heterocyclic compounds in high yields has been described. Moreover, two phenylsulfonyl groups installed on the heterocyclic products could be conveniently removed or transformed to other functional groups, making the reaction more useful.     

Transition-Metal-Free Three-Component Radical 1,2-Amidoalkynylation of Unactivated Alkenes

A transition-metal-free radical 1,2-amidoalkynylation of unactivated alkenes is presented. α-Amido-oxy acids were used as amidyl radical precursors, which were oxidized by an organic photoredox catalyst (4CzlPN). The electrophilic N-radicals chemoselectively reacted with various aliphatic alkenes and the adduct radicals were then trapped by ethynylbenziodoxolone (EBX) reagents to eventually provide the amidoalkynylation products. These transformations, which were conducted under practical and mild conditions, showed high functional group tolerance and broad substrate scope. Mechanistic studies supported the radical nature of these cascades.     

Development,Scope and Mechanisms of Multicomponent Reactions of Asymmetric Electron‐Deficient Alkynes with Amines and Formaldehyde

Based on the reactive behaviour of the substrates, two synthetic routes to polysubstituted pyrimidine derivatives are presented herein: 1) A catalyst‐free multicomponent reaction of electron‐deficient alkynes, aliphatic amines and formaldehyde and 2) Ag^I‐catalyzed synthesis of pyrimidines from electron‐deficient alkynes, anilines and formaldehyde by a domino reaction. Under optimized conditions, the multicomponent reactions were accomplished with high regioselectivity and excellent yields. A computational study was carried out by using the B3LYP density functional theory to elucidate the mechanisms of the catalyst‐free hydroamination reaction. Calculations showed the activation free energies of aliphatic amines were lower than those of anilines, which is consistent with the experimental results.     

Copper‐Catalyzed Oxyboration of Unactivated Alkenes

The first regiodivergent oxyboration of unactivated terminal alkenes is reported, using copper alkoxide as a catalyst, bis(pinacolato)diboron [(Bpin)₂] as a boron source, and (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) as an oxygen source. The reaction is compatible with various functional groups. Two regioisomers are selectively produced by selecting the appropriate ligands on copper. The products may be used as a linchpin precursor for various other functionalizations, and net processes such as carbooxygenation, aminooxygenation, and dioxygenation of alkenes can be achieved after C?B bond transformations. Mechanistic studies indicate that the reaction involves the following steps: 1) Transmetalation between CuOtBu and (Bpin)₂ to generate a borylcopper species; 2) regiodivergent borylcupration of alkenes; 3) oxidation of the thus‐generated C?Cu bond to give an alkyl radical; 4) trapping of the resulting alkyl radical by TEMPO.     

Photoredox‐Catalyzed Alkenylation of Benzylsulfonium Salts

Visible light‐mediated radical alkenylation of benzylsulfonium salts was achieved by means of fac‐Ir(ppy)₃ as a photocatalyst, giving allylbenzenes as products. A variety of functional groups, such as halogen, ester, and cyano, were well tolerated in this transformation. Starting benzylsulfonium salts could be readily prepared from benzyl alcohols by an acid‐mediated substitution, increasing the synthetic utility of this transformation.     

Nickel‐Catalyzed Asymmetric Reductive 1,2‐Carboamination of Unactivated Alkenes

Starting from diverse alkene‐tethered aryl iodides and O‐benzoyl‐hydroxylamines, the enantioselective reductive cross‐electrophilic 1,2‐carboamination of unactivated alkenes was achieved using a chiral pyrox/nickel complex as the catalyst. This mild, modular, and practical protocol provides rapid access to a variety of β‐chiral amines with an enantioenriched aryl‐substituted quaternary carbon center in good yields and with excellent enantioselectivities. This process reveals a complementary regioselectivity when compared to Pd and Cu catalysis.     

Copper‐Catalyzed Aerobic Decarboxylation/Ketooxygenation of Electron‐Deficient Alkenes

A copper‐catalyzed ketooxygenation of electron‐deficient alkenes was developed. This approach combines O?H alkylation, aerobic decarboxylation, and oxygenation in one transformation. Mechanistic investigation of this reaction showed that the copper salt is responsible for both generating the amidoxyl radical and promoting aerobic decarboxylation.     

anti‐Markovnikov Hydroamination of Alkenes Catalyzed by a Two‐Component Organic Photoredox System: Direct Access to Phenethylamine Derivatives

Disclosed herein is a general catalytic system for the intermolecular anti‐Markovnikov hydroamination of alkenes. By using an organocatalytic photoredox system, α‐ and β‐substituted styrenes as well as aliphatic alkenes undergo anti‐Markovnikov hydroamination. Heterocyclic amines were also successfully employed as nitrogen nucleophiles, thus providing a direct route to heterocyclic motifs common in medicinal agents.     

Pd‐Catalyzed Difluoromethylation of Vinyl Bromides,Triflates, Tosylates,and Nonaflates

Pd‐catalyzed difluoromethylation of di‐, tri‐ or tetra‐substituted vinyl bromides, triflates, tosylates and nonaflates under mild conditions is described. The reaction tolerates a wide range of functional groups, such as bromide, chloride, fluoride, ester, amine, nitrile, and protected carbonyl, thus providing a general route for the preparation of difluoromethylated alkenes.     

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.     

Synthesis of trans‐Disubstituted Alkenes by Cobalt‐Catalyzed Reductive Coupling of Terminal Alkynes with Activated Alkenes

A cobalt‐catalyzed reductive coupling of terminal alkynes, RC?CH, with activated alkenes, R′CH?CH₂, in the presence of zinc and water to give functionalized trans‐disubstituted alkenes, RCH?CHCH₂CH₂R′, is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl₂/P(OMe)₃/Zn catalyst system to afford 1,2‐trans‐disubstituted alkenes with high regio‐ and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl₂/P(OPh)₃/Zn system providing a mixture of 1,2‐trans‐ and 1,1‐disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3‐enynes and acetylene gas with alkenes. Furthermore, a phosphine‐free cobalt‐catalyzed reductive coupling of terminal alkynes with enones, affording 1,2‐trans‐disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air‐stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed.     

Palladium‐Catalyzed para‐Selective Alkylation of Electron‐Deficient Arenes

Intermolecular alkylations of electron‐deficient arenes proceed with good para selectivity. Palladium catalysts were used to generate nucleophilic alkyl radicals from alkyl halides, which then directly add onto the arenes. The arene scope and the site of alkylation are opposite to those of classical Friedel–Crafts alkylations, which prefer electron‐rich systems.