Pyridine‐Enhanced Head‐to‐Tail Dimerization of Terminal Alkynes by a Rhodium–N‐Heterocyclic‐Carbene Catalyst

A general regioselective rhodium‐catalyzed head‐to‐tail dimerization of terminal alkynes is presented. The presence of a pyridine ligand (py) in a Rh–N‐heterocyclic‐carbene (NHC) catalytic system not only dramatically switches the chemoselectivity from alkyne cyclotrimerization to dimerization but also enhances the catalytic activity. Several intermediates have been detected in the catalytic process, including the π‐alkyne‐coordinated Rh^I species [RhCl(NHC)(η²‐HC?CCH₂Ph)(py)] ( 3 ) and [RhCl(NHC){η²‐C(tBu)?C(E)CH?CHtBu}(py)] ( 4 ) and the Rh^III–hydride–alkynyl species [RhClH{? C?CSi(Me)₃}(IPr)(py)₂] ( 5 ). Computational DFT studies reveal an operational mechanism consisting of sequential alkyne C? H oxidative addition, alkyne insertion, and reductive elimination. A 2,1‐hydrometalation of the alkyne is the more favorable pathway in accordance with a head‐to‐tail selectivity.     

Highly modulated bisindoles: ligands for copper‐catalyzed Sonogashira reaction

Bisindoles (BIMs) were modulated as powerful N,N′ donor ligands for the copper‐catalyzed Sonogashira reaction. Ligand screening experiments on 11 BIM compounds found that 3,3′‐(4‐chlorophenyl)methylenebis(1‐methyl‐1H‐indole) (10%) efficiently accelerated CuCl (5%)‐catalyzed cross‐coupling of aryl iodides with terminal alkynes. A wide range of substituted aryl iodides and/or alkyl‐ and aryl‐substituted terminal alkynes were examined, leading to the corresponding coupling products with yields up to 99%. An efficient and scalable protocol for the synthesis of BIM ligands on a gram scale, with extremely low catalyst loading of o‐ClC₆H₄NH₃⁺Cl^?, was also developed with a reaction time of 20 min with yields up to 93%. This novel N,N′ ligand was air‐stable, easily available and highly modulated with low copper loading. Copyright © 2016 John Wiley & Sons, Ltd.     

Dihydrobiphenylenes through Ruthenium‐Catalyzed [2+2+2] Cycloadditions of ortho‐Alkenylarylacetylenes with Alkynes

A new synthetic route to dihydrobiphenylenes has been developed. The process involves a mild Ru^II‐catalyzed [2+2+2] dimerization of ortho‐alkenylarylacetylenes or its more versatile variant, the Ru‐catalyzed [2+2+2] cycloaddition of ortho‐ethynylstyrenes with alkynes. Mechanistic aspects of this [2+2+2] cycloaddition are discussed.     

Novel pyridine‐bis(ferrocene‐isoxazole) ligand: synthesis and application to palladium‐catalyzed Sonogashira cross‐coupling reactions under copper‐ and phosphine‐free conditions

We present here the first synthesis and application to Sonogashira reaction of pyridine‐bis(ferrocene‐isoxazole) Pd(II) complex 5 , prepared from 2,6‐bis‐(5‐ferrocenylisoxazole‐3‐yl)pyridine. Under copper‐ and phosphine‐free conditions, the stable complex 5 efficiently catalyzed the cross‐coupling of aryl halides with terminal alkynes in DMF–H₂O with TBAB as an additive, hexahydropyridine as base and affording internal arylated alkynes in moderate to excellent yields. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

Diastereo‐ and Enantioselective Synthesis of (E)‐δ‐Boryl‐Substituted anti‐Homoallylic Alcohols in Two Steps from Terminal Alkynes

We report the highly diastereo‐ and enantioselective preparation of (E)‐δ‐boryl‐substituted anti‐homoallylic alcohols in two steps from terminal alkynes. This method consists of a cobalt(II)‐catalyzed 1,1‐diboration reaction of terminal alkynes with B₂pin₂ and a palladium(I)‐mediated asymmetric allylation reaction of the resulting 1,1‐di(boryl)alk‐1‐enes with aldehydes in the presence of a chiral phosphoric acid. Propyne, which is produced as the byproduct during petroleum refining, could be used as the starting material to construct homoallylic alcohols that are otherwise difficult to synthesize with high stereocontrol.     

Cobalt‐Catalyzed Z‐Selective Hydrosilylation of Terminal Alkynes

A cobalt‐catalyzed Z ‐selective hydrosilylation of alkynes has been developed relying on catalysts generated from bench‐stable Co(OAc)₂ and pyridine‐2,6‐diimine (PDI) ligands. A variety of functionalized aromatic and aliphatic alkynes undergo this transformation, yielding Z ‐vinylsilanes in high yields with excellent selectivities (Z /E ratio ranges from 90:10 to >99:1). The addition of a catalytic amount of phenol effectively suppressed the Z /E ‐isomerization of the Z ‐vinylsilanes that formed under catalytic conditions.     

[5+2] Cycloaddition of 2‐(2‐Aminoethyl)oxiranes with Alkynes via Epoxide Ring‐Opening: A Facile Access to Azepines

A new FeCl₃ and BF₃?OEt₂ co‐catalyzed tandem hetero‐[5+2] cycloaddition of 2‐(2‐aminoethyl)oxiranes with a wide range of alkynes, including terminal alkynes and alkyl‐substituted internal alkynes is presented. This is the first example of rapid and facile production of diverse 2,3‐dihydro‐1H‐azepines through a sequence of epoxide ring‐opening, annulation, and dehydroxylation with broad substrate scope and exquisite selectivity control.     

First report of a nano‐Cu2O‐catalyzed protocol for homo‐coupling reaction of terminal alkynes in water/ionic liquid medium

A new, efficient and green protocol for the nano‐Cu₂O‐catalyzed homo‐coupling reaction of terminal alkynes has been developed, using water/ionic liquid as an environmentally friendly solvent. Moreover, the system also allows the synthesis of unsymmetric 1,3‐diynes by cross‐coupling of two different terminal alkynes. It is noteworthy that the nano‐Cu₂O‐catalyzed methodology is a good supplement to copper catalyst for the Glaser‐type homo‐coupling reaction. Copyright © 2016 John Wiley & Sons, Ltd.     

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.     

Synthesis of Silaphenalenes by Ruthenium‐Catalyzed Annulation between 1‐Naphthylsilanes and Internal Alkynes through CH Bond Cleavage

Ruthenium‐catalyzed annulation of 1‐naphthylsilanes with internal alkynes afforded silaphenalenes through cleavage of the C?H bond at the 8‐position of the naphthalene. [RuH₂(CO){P(p‐FC₆H₄)₃}₃] efficiently catalyzed the reaction. The use of 1‐naphthyldiphenylsilane as a substrate resulted in a better yield of the annulation product compared to the use of silanes with alkyl groups on the silicon atom. Internal alkynes with both aryl and alkyl groups were tolerated in this reaction.     

Cobalt‐Catalyzed E‐Selective Cross‐Dimerization of Terminal Alkynes: A Mechanism Involving Cobalt(0/II) Redox Cycles

A highly E‐selective cross‐dimerization of terminal alkynes with either terminal silylacetylenes, tert‐butylacetylene, or 1‐trimethylsilyloxy‐1,1‐diphenyl‐2‐propyne in the presence of a dichlorocobalt(II) complex bearing a sterically demanding 2,9‐bis(2,4,6‐triisopropylphenyl)‐1,10‐phenanthroline, activated with two equivalents of EtMgBr, gives a variety of (E)‐1,3‐enynes. A well‐characterized diolefin/cobalt(0) complex, with divinyltetramethyldisiloxane, acted as a catalytically active species without any activation, clearly indicating that a cobalt(0) species is involved in the catalytic cycle.     

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.     

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.     

Iron‐Catalyzed Diboration and Carboboration of Alkynes

An iron‐catalyzed diboration reaction of alkynes with bis(pinacolato)diboron (B₂pin₂) and external borating agents (MeOB(OR)₂) affords diverse symmetrical or unsymmetrical cis‐1,2‐diborylalkenes. The simple protocol for the diboration reaction can be extended to the iron‐catalyzed carboboration of alkynes with primary and, unprecedentedly, secondary alkyl halides, affording various tetrasubstituted monoborylalkenes in a highly stereoselective manner. DFT calculations indicate that a boryliron intermediate adds across the triple bond of an alkyne to afford an alkenyliron intermediate, which can react with the external trapping agents, borates and alkyl halides. In situ trapping experiments support the intermediacy of the alkenyl iron species using radical probe stubstrates.     

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.     

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.     

Nickel‐Catalyzed Cyclization of ortho‐Iodoketoximes and ortho‐Iodoketimines with Alkynes: Synthesis of Highly Substituted Isoquinolines and Isoquinolinium Salts

A convenient method for the synthesis of highly substituted isoquinolines and isoquinolinium salts by the nickel‐catalyzed cyclization of ortho‐haloketoximes and ‐ketimines, respectively, with alkynes is described. The reaction of ortho‐haloketoximes and various alkynes in the presence of [Ni(PPh₃)₂Br₂] and zinc powder in a mixture of acetonitrile and tetrahydrofuran at 80 °C for 15 hours gave 1,3,4‐trisubstituted isoquinoline products in moderate to excellent yields and high regioselectivity. The corresponding isoquinoline N‐oxide was found to be the intermediate in the cyclization reaction pathway. In contrast, the reaction of ortho‐haloketimines and alkynes under similar catalytic conditions in tetrahydrofuran at 70 °C for two hours gave 1,2,3,4‐tetrasubstituted isoquinolinium salts in good to excellent yields.     

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.     

Catalytic Enantioselective Cyclopropenation of Internal Alkynes: Access to Difluoromethylated Three‐Membered Carbocycles

Herein we described an efficient Rh^II‐catalyzed enantioselective cyclopropenation reaction of internal alkynes with a masked difluorodiazoethane reagent (PhSO₂CF₂CHN₂, Ps‐DFA). This asymmetric transformation offers efficient access to a broad range of enantioenriched difluoromethylated cyclopropenes (40 examples, up to 99 % yield, 97 % ee). The synthetic utility of obtained strained carbocycles is demonstrated by subsequent stereodefined processes, including cross‐couplings, hydrogenation, Diels–Alder reaction, and Pauson–Khand reaction.