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.     

Calcium‐Catalyzed Carboarylation of Alkynes

The first transition‐metal‐free carboarylation of alkynes with commercial and readily available alcohols as alkylating agents was realized in the presence of an environmentally benign calcium catalyst. Thereby, a novel protocol for the one‐step synthesis of highly congested, all‐carbon tetrasubstituted alkenes, as incorporated in potentially bioactive, complex dihydronaphthalene, chromene and dihydroquinoline structures, is provided. The reaction features an unprecedented, particularly wide substrate scope, good functional‐group tolerance and simple experimental operation under mild reaction conditions.     

Copper‐Catalyzed Stereoselective Aminoboration of Bicyclic Alkenes

A copper‐catalyzed aminoboration of bicyclic alkenes, including oxa‐ and azabenzonorbornadienes, has been developed. With this method, amine and boron moieties are simultaneously introduced at an olefin with exo selectivity. Subsequent stereospecific transformations of the boryl group can provide oxygen‐ and nitrogen‐rich cyclic molecules with motifs that may be found in natural products or pharmaceutically active compounds. Moreover, a catalytic asymmetric variant of this transformation was realized by using a copper complex with a chiral bisphosphine ligand, namely (R,R)‐Ph‐BPE.     

Selective Ruthenium‐Catalyzed Hydrochlorination of Alkynes: One‐Step Synthesis of Vinylchlorides

An unprecedented ruthenium‐catalyzed direct and selective alkyne hydrochlorination is reported and leads to vinylchlorides in excellent yields with atom economy. The reaction proceeds at room temperature from terminal alkynes and provides a variety of chloroalkenes. Only the regioisomer resulting from the formal Markovnikov addition is selectively formed. Mechanistic studies show the stereoselective syn addition of HCl to alkynes at room temperature and suggest a chloro hydrido Ru^IV species as a key intermediate of the reaction.     

Copper‐Catalyzed Borocarbonylative Coupling of Internal Alkynes with Unactivated Alkyl Halides: Modular Synthesis of Tetrasubstituted β‐Borylenones

Reported is a general procedure to synthesize tetrasubstituted enones, which are borylated in the β‐position, using a copper‐catalyzed four‐component coupling reaction of simple chemical feedstocks: internal alkynes, alkyl halides, bis(pinacolato)diboron (B₂pin₂), and CO. A broad scope of highly functionalized β‐borylated enones, a largely unknown class of organic compounds, can be accessed efficiently using this method. The synthesis of all‐carbon tetrasubstituted enones was realized by employing the β‐borylated enone unit, without purification, in a Suzuki–Miyaura coupling. The utility of the method was further demonstrated by various transformations, including halogenation, oxidation, and protodeboration, of the corresponding reduced oxaborole species to provide densely substituted allylic alcohol and ketone products.     

Ruthenium‐Catalyzed Oxidation of Alkenes,Alkynes, and Alcohols to Organic Acids with Aqueous Hydrogen Peroxide

A protocol that adopts aqueous hydrogen peroxide as a terminal oxidant and [(Me₃tacn)(CF₃CO₂)₂Ru^III(OH₂)]CF₃CO₂ ( 1 ; Me₃tacn=1,4,7‐trimethyl‐1,4,7‐triazacyclononane) as a catalyst for oxidation of alkenes, alkynes, and alcohols to organic acids in over 80 % yield is presented. For the oxidation of cyclohexene to adipic acid, the loading of 1 can be lowered to 0.1 mol %. On the one‐mole scale, the oxidation of cyclohexene, cyclooctene, and 1‐octanol with 1 mol % of 1 produced adipic acid (124 g, 85 % yield), suberic acid (158 g, 91 % yield), and 1‐octanoic acid (129 g, 90 % yield), respectively. The oxidative C?C bond‐cleavage reaction proceeded through the formation of cis‐ and trans‐diol intermediates, which were further oxidized to carboxylic acids via C? C bond cleavage.     

Ruthenium‐Catalyzed trans‐Selective Hydrostannation of Alkynes

In contrast to all other transition‐metal‐catalyzed hydrostannation reactions documented in the literature, the addition of Bu₃SnH across various types of alkynes proceeds with excellent trans selectivity, provided the reaction is catalyzed by [Cp*Ru]‐based complexes. This method is distinguished by a broad substrate scope and a remarkable compatibility with functional groups, including various substituents that would neither survive under the conditions of established Lewis acid mediated trans hydrostannations nor withstand free‐radical reactions. In case of unsymmetrical alkynes, a cooperative effect between the proper catalyst and protic functionality in the substrate allows outstanding levels of regioselectivity to be secured as well.     

Highly Chemo‐, Regio‐, and Enantioselective Rhodium‐Catalyzed Cross‐Cyclotrimerization of Two Different Alkynes with Alkenes

It has been established that a cationic rhodium(I)/(R)‐tol‐binap complex catalyzes the cross‐cyclotrimerization of silylacetylenes, di‐tert‐butyl acetylenedicarboxylates, and acrylamides with excellent chemo‐, regio‐, and enantioselectivities. Unsymmetrical alkynoates can also be employed in place of di‐tert‐butyl acetylenedicarboxylate for this process, but with reduced chemoselectivity.     

Nickel‐Catalyzed Stereoselective Dicarbofunctionalization of Alkynes

A nickel‐catalyzed three‐component reaction involving terminal alkynes, boronic acids, and alkyl halides is presented herein. Trisubstituted alkenes can be obtained in a highly regio‐ and stereocontrolled manner by the simultaneous addition of both aryl and alkyl groups across the triple bond in a radical‐mediated process. The reaction, devoid of air‐ and moisture‐sensitive organometallic reagents and catalysts, is operationally simple and offers a broad scope and functional‐group tolerance.     

Palladium‐Catalyzed Formal Hydroalkylation of Aryl‐Substituted Alkynes with Hydrazones

We have developed an unprecedented Pd‐catalyzed formal hydroalkylation of alkynes with hydrazones, which are generated in situ from naturally abundant aldehydes, as both alkylation reagents and hydrogen donors. The hydroalkylation proceeds with high regio‐ and stereoselectivity to form (Z)‐alkenes, which are more difficult to generate compared to (E)‐alkenes. The reaction is compatible with a wide range of functional groups, including hydroxy, ester, ketone, nitrile, boronic ester, amine, and halide groups. Furthermore, late‐stage modifications of natural products and pharmaceutical derivatives exemplify its unique chemoselectivity, regioselectivity, and synthetic applicability. Mechanistic studies indicate the possible involvement of Pd‐hydride intermediates.     

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.     

Cobalt‐Catalyzed Alkenylzincation of Unfunctionalized Alkynes

While transition metal catalyzed addition reactions of arylmetal reagents to unfunctionalized alkynes have been extensively developed in the last decade, analogous reactions using alkenylmetal reagents remain rare regardless of their potential utility for the synthesis of unsymmetrical 1,3‐dienes. Reported herein is the development of a cobalt/diphosphine catalyst which promotes efficient and stereoselective addition of alkenylzinc reagents to unfunctionalized internal alkynes. The resulting dienylzinc species serve as versatile intermediates for further synthetic transformations.