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?CH(2) , in the presence of zinc and water to give functionalized trans-disubstituted alkenes, RCH?CHCH(2) CH(2) R', 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 CoCl(2) /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 CoCl(2) /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.     

Cobalt-catalyzed reductive coupling of activated alkenes with alkynes

Cobalt complex/Zn systems effectively catalyze the reductive coupling of activated alkenes with alkynes in the presence of water to give substituted alkenes with very high regio- and stereoselectivity in excellent yields. While the intermolecular reaction of acrylates, acrylonitriles, and vinyl sulfones with alkynes takes place in the presence of CoI2(PPh3)2/Zn, the reaction of enones and enals with alkynes requires the use of the CoI2(dppe)/Zn/ZnI2 system. The intramolecular reductive coupling of activated alkenes (enones, enals, acrylates, and acrylonitriles) with alkynes also works efficiently. Further a variety of cyclic lactones and lactams were prepared using this methodology. Possible mechanistic pathways are proposed based on a deuterium-labeling experiment carried out in the presence of D2O.     

Palladium‐Catalyzed Reductive Coupling Reaction of Terminal Alkynes with Aryl Iodides Utilizing Hafnocene Difluoride as a Hafnium Hydride Precursor Leading to trans‐Alkenes

Herein, we describe a reductive cross‐coupling of alkynes and aryl iodides by using a novel catalytic system composed of a catalytic amount of palladium dichloride and a promoter precursor, hafnocene difluoride (Cp₂HfF₂, Cp=cyclopentadienyl anion), in the presence of a mild reducing reagent, a hydrosilane, leading to a one‐pot preparation of trans‐alkenes. In this process, a series of coupling reactions efficiently proceeds through the following three steps: (i) an initial formation of hafnocene hydride from hafnocene difluoride and the hydrosilane, (ii) a subsequent hydrohafnation toward alkynes, and (iii) a final transmetalation of the alkenyl hafnium species to a palladium complex. This reductive coupling could be chemoselectively applied to the preparation of trans‐alkenes with various functional groups, such as an alkyl group, a halogen, an ester, a nitro group, a heterocycle, a boronic ester, and an internal alkyne.     

Iron‐Catalyzed 1,2‐Addition of Perfluoroalkyl Iodides to Alkynes and Alkenes

Iron catalysis has been developed for the intermolecular 1,2‐addition of perfluoroalkyl iodides to alkynes and alkenes. The catalysis has a wide substrate scope and high functional‐group tolerance. A variety of perfluoroalkyl iodides including CF₃I can be employed. The resulting perfluoroalkylated alkyl and alkenyl iodides can be further functionalized by cross‐coupling reactions. This methodology provides a straightforward and streamlined access to perfluoroalkylated organic molecules.     

Palladium/Copper‐Catalyzed Oxidative Arylation of Terminal Alkenes with Aroyl Hydrazides

An unprecedented oxidative arylation reaction of terminal alkenes with simple aroyl hydrazides has been developed under aerobic conditions for the stereoselective synthesis of 1,2‐disubstituted alkenes. A range of aroyl hydrazides underwent palladium/copper‐catalyzed oxidative Mizoroki–Heck reaction with terminal alkenes open to air in a 1:1 mixture of dimethyl sulfoxide and acetonitrile to give structurally diverse 1,2‐disubstituted alkenes in moderate to excellent yields with excellent regio‐ and E‐selectivity. The reaction tolerated a wide variety of functional groups, such as alkoxy, hydroxy, amino, fluoro, chloro, bromo, cyano, nitro, ester, amide, imide, phosphine oxide, and sulfone groups, and, moreover, molecular oxygen and dimethyl sulfoxide were demonstrated to serve as terminal oxidants. This study provides a useful method for the stereoselective synthesis of 1,2‐disubstituted alkenes through direct transformation of the vinylic C?H bonds in terminal alkenes.     

Construction of Quaternary Stereogenic Carbon Centers through Copper‐Catalyzed Enantioselective Allylic Cross‐Coupling with Alkylboranes

A combination of an in situ generated chiral Cu^I/DTBM‐MeO‐BIPHEP catalyst system and EtOK enabled the enantioselective S_N2′‐type allylic cross‐coupling between alkylborane reagents and γ,γ‐disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp³‐alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross‐coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.     

Stereoselective Synthesis of Trisubstituted Alkenes through Sequential Iron‐Catalyzed Reductive anti‐Carbozincation of Terminal Alkynes and Base‐Metal‐Catalyzed Negishi Cross‐Coupling

The stereoselective synthesis of trisubstituted alkenes is challenging. Here, we show that an iron‐catalyzed anti‐selective carbozincation of terminal alkynes can be combined with a base‐metal‐catalyzed cross‐coupling to prepare trisubstituted alkenes in a one‐pot reaction and with high regio‐ and stereocontrol. Cu‐, Ni‐, and Co‐based catalytic systems are developed for the coupling of sp‐, sp²‐, and sp³‐hybridized carbon electrophiles, respectively. The method encompasses a large substrate scope, as various alkynyl, aryl, alkenyl, acyl, and alkyl halides are suitable coupling partners. Compared with conventional carbometalation reactions of alkynes, the current method avoids pre‐made organometallic reagents and has a distinct stereoselectivity.     

Iron‐Catalyzed Regioselective Transfer Hydrogenative Couplings of Unactivated Aldehydes with Simple Alkenes

An FeBr₃‐catalyzed reductive coupling of various aldehydes with alkenes that proceeds through a direct hydride transfer pathway has been developed. With ⁱPrOH as the hydrogen donor under mild conditions, previously challenging coupling reactions of unactivated alkyl and aryl aldehydes with simple alkenes, such as styrene derivatives and α‐olefins, proceeded smoothly to furnish a diverse range of functionalized alcohols with complete linear regioselectivity.     

A Robust and Broadly Applicable Cobalt‐Catalyzed Cross‐Coupling of Functionalized Bench‐Stable Organozinc Pivalates with Unsaturated Halides

We report a robust and broadly applicable CoCl₂‐catalyzed cross‐coupling between functionalized aryl and heteroaryl zinc pivalates and various electron‐poor aryl and heteroaryl halides (X=Cl, Br, I). Couplings with (E)‐ or (Z)‐bromo‐ or iodo‐alkenes proceed with retention of configuration. Also, alkynyl bromides react with arylzinc pivalates providing arylated alkynes.     

Highly Regio‐ and Stereoselective Hydrosilylation of Alkynes Catalyzed by Tridentate Cobalt Complexes

Several cobalt complexes bearing tridentate (NNN) ligands were synthesized and served as precatalysts for alkyne hydrosilylation with Ph₂SiH₂. For terminal alkynes, the catalyst L2 b‐CoCl₂ was selected, and resulted in the corresponding α‐vinylsilanes with high (Markovnikov) regioselectivity and extensive functional‐group tolerance. For internal diaryl alkynes, the catalyst L2 c‐CoCl₂ exhibited the best activity, and afforded E‐selective vinylsilanes through syn‐addition in excellent yield under mild conditions.     

Redox‐Divergent Synthesis of Fluoroalkylated Pyridines and 2‐Pyridones through Cu‐Catalyzed N−O Cleavage of Oxime Acetates

Cu‐catalyzed redox‐divergent [3+3] coupling of oxime esters with β‐CF₃ enones and acrylates is described. This redox‐neutral coupling with enones and acrylates affords trifluoromethylated pyridines and pyridones, respectively. Under reductive conditions, difluoromethylated pyridines, difluoromethlated pyridones, and trifluoromethylated dihydropyridones are obtained. The reactions occur under mild conditions with broad substrate scope and regio/redox selectivity.     

Enantiospecific Alkynylation of Alkylboronic Esters

Enantioenriched secondary and tertiary alkyl pinacolboronic esters undergo enantiospecific deborylative alkynylation through a Zweifel‐type alkenylation followed by a 1,2‐elimination reaction. The process involves use of α‐lithio vinyl bromide or vinyl carbamate species, for which application to Zweifel‐type reactions has not previously been explored. The resulting functionalized 1,1‐disubstituted alkenes undergo facile base‐mediated elimination to generate terminal alkyne products in high yield and excellent levels of enantiospecificity over a wide range of pinacolboronic ester substrates. Furthermore, along with terminal alkynes, internal and silyl‐protected alkynes can be formed by simply introducing a suitable carbon‐ or silicon‐based electrophile after the base‐mediated 1,2‐elimination reaction.     

Combined Experimental and Computational Investigations of Rhodium‐Catalysed CH Functionalisation of Pyrazoles with Alkenes

Detailed experimental and computational studies have been carried out on the oxidative coupling of the alkenes C₂H₃Y (Y=CO₂Me ( a ), Ph ( b ), C(O)Me ( c )) with 3‐aryl‐5‐R‐pyrazoles (R=Me ( 1 a ), Ph ( 1 b ), CF₃ ( 1 c )) using a [Rh(MeCN)₃Cp*][PF₆]₂/Cu(OAc)₂ ? H₂O catalyst system. In the reaction of methyl acrylate with 1 a , up to five products ( 2 aa – 6 aa ) were formed, including the trans monovinyl product, either complexed within a novel Cu^I dimer ( 2 aa ) or as the free species ( 3 aa ), and a divinyl species ( 6 aa ); both 3 aa and 6 aa underwent cyclisation by an aza‐Michael reaction to give fused heterocycles 4 aa and 5 aa , respectively. With styrene, only trans mono‐ and divinylation products were observed, whereas with methyl vinyl ketone, a stronger Michael acceptor, only cyclised oxidative coupling products were formed. Density functional theory calculations were performed to characterise the different migratory insertion and β‐H transfer steps implicated in the reactions of 1 a with methyl acrylate and styrene. The calculations showed a clear kinetic preference for 2,1‐insertion and the formation of trans vinyl products, consistent with the experimental results.     

An Alternative Mechanism for the Cobalt‐Catalyzed Isomerization of Terminal Alkenes to (Z)‐2‐Alkenes

The cobalt‐catalyzed selective isomerization of terminal alkenes to the thermodynamically less‐stable (Z)‐2‐alkenes at ambient temperatures takes place by a new mechanism involving the transfer of a hydrogen atom from a Ph₂PH ligand to the starting material and the formation of a phosphenium complex, which recycles the Ph₂PH complex through a 1,2‐H shift.     

Rhodium‐Catalyzed Intermolecular trans‐Disilylation of Alkynones with Unactivated Disilanes

Disilylation of alkynes could provide rapid entry to synthetically useful 1,2‐bissilyl‐alkenes, but is currently limited to activated disilanes reacting in an intramolecular fashion. Reported herein is an efficient rhodium(I)‐catalyzed intermolecular disilylation of a wide array of alkynones with unactivated disilanes. Importantly, this reaction produces exclusively trans‐disilylation products, selectivity that has been rarely reported. These disilylation products were transformed into interesting pentacyclic vinyl silane ethers, among other additional synthetic manipulations. Mechanistic studies uncovered that the unactivated disilanes underwent facile Si?Si activation and crossover under the reaction conditions.     

Catalytic CN Bond Alkynylation of N‐Benzylic Sulfonamides with Terminal Alkynes

A new cross‐coupling reaction of N‐benzylic sulfonamides with terminal alkynes for the synthesis of internal alkynes is reported. In the presence of 5 mol% of (Tf)₂NH/Bi(OTf)₃ (1:1), a broad range of N‐benzylic sulfonamides react smoothly with arylacetylenes to afford structurally diverse internal alkynes in moderate to excellent yields. We reasoned that vinyl cations could be formed by the regioselective attack of terminal alkynes with benzyl cations generated in situ from N‐benzylic sulfonamides under acidic conditions, which then eliminated to form a carbon‐carbon triple bond.     

An Alkene‐Promoted Borane‐Catalyzed Highly Stereoselective Hydrogenation of Alkynes to Give Z‐ and E‐Alkenes

The stereoselective hydrogenation of alkynes to alkenes is an extremely useful transformation in synthetic chemistry. Despite numerous reports for the synthesis of Z‐alkenes, the hydrogenation of alkynes to give E‐alkenes is still not well resolved. In particular, selective preparation of both Z‐ and E‐alkenes by the same catalytic hydrogenation system using molecular H₂ has rarely been reported. In this paper, a novel strategy of using simple alkenes as promoters for the HB(C₆F₅)₂‐catalyzed metal‐free hydrogenation of alkynes was adopted. Significantly, both Z‐ and E‐alkenes can be furnished by hydrogenation with molecular H₂ in high yields with excellent stereoselectivities. Further experimental and theoretical mechanistic studies suggest that interactions between H and F atoms of the alkene promoter, borane intermediate, and H₂ play an essential role in promoting the hydrogenolysis reaction.     

Regio‐ and Stereoselective Reductive Coupling of Bicyclic Alkenes with Propiolates Catalyzed by Nickel Complexes: A Novel Route to Functionalized 1,2‐Dihydroarenes and γ‐Lactones

7‐Oxabenzonorbornadienes derivatives 1 a – d underwent reductive coupling with alkyl propiolates CH₃C?CCO₂CH₃ ( 2 a ), PhC?CCO₂Et ( 2 b ), CH₃(CH₂)₃C?CCO₂CH₃ ( 2 c ), CH₃(CH₂)₄C?CCO₂CH₃ ( 2 d ), TMSC?CCO₂Et ( 2 e ), (CH₃)₃C?CCO₂CH₃ ( 2 f ) and HC?CCO₂Et ( 2 g ) in the presence of [NiBr₂(dppe)] (dppe=Ph₂PCH₂CH₂PPh₂), H₂O and zinc powder in acetonitrile at room temperature to afford the corresponding 2alkenyl‐1,2‐dihydronapthalen‐1‐ol derivatives 3 a – n with remarkable regio‐ and diastereoselectivity in good to excellent yields. Similarly, the reaction of 7azabenzonorbornadienes derivative 1 e with propiolates 2 a, b and d proceeded smoothly to afford reductive coupling products 2alkenyl‐1,2‐dihydronapthalene carbamates 3 o – p in good yields with high regio‐ and stereoselectivity. This nickel‐catalyzed reductive coupling can be further extended to the reaction of 7oxabenzonorbornene derivatives. Thus, 5,6‐di(methoxymethyl)‐7‐oxabicyclo[2.2.1]hept‐2‐ene ( 4 ) reacted with 2 a and 2 d to furnish cyclohexenol derivatives bearing four cis substituents 5 a and b in 81 and 84 % yield, respectively. In contrast to the results of 4 with 2 , the reaction of dimethyl 7oxabicyclo[2.2.1]hept‐5‐ene‐2,3‐dicarboxylate ( 6 ) with propiolates 2 a – d afforded the corresponding reductive coupling/cyclization products, bicyclo[3.2.1]γ‐lactones 7 a – d in good yields. The reaction provides a convenient one‐pot synthesis of γ‐lactones with remarkably high regio‐ and stereoselectivity.     

Oxidant promoted 1,3‐dipolar cycloaddition of benzimidazolium ylides to alkenes for preparation of 4H‐pyrrolo[1,2‐a]benzimidazole

An oxidant promoted 1,3‐dipolar cycloaddition of benzimidazolium ylides to alkenes was developed for the preparation of 4H‐pyrrolo[1,2‐a]benzimidazole derivatives in moderate yields under mild conditions. In the presence of a suitable oxidant, the most commercially available “normal” alkenes, instead of alkynes or “abnormal” alkenes, could be used as dipolarophiles successfully. Moreover, CrO₃/Et₃N has been proved to be a more effective dehydrogenating reagent than MnO₂ or tetrakispyridine cobalt (II) dichromate (TPCD) in this procedure.     

Modular Access to the Stereoisomers of Fused Bicyclic Azepines: Rhodium‐Catalyzed Intramolecular Stereospecific Hetero‐[5+2] Cycloaddition of Vinyl Aziridines and Alkenes

The first rhodium‐catalyzed intramolecular hetero‐[5+2] cycloaddition reaction of vinyl aziridines and alkenes was realized, wherein both internal and terminal alkenes were applicable. With this method, a variety of unique substituted chiral fused bicyclic azepines, bearing multiple contiguous stereogenic centers, were facilely accessed in a straightforward, high‐yielding, and highly stereoselective manner under mild reaction conditions. Notably, the E/Z geometry of the C?C bonds in the vinyl aziridine‐alkene substrates impact the cis/trans stereochemistry of the cycloadducts and up to six stereoisomers could be delivered.