Iron‐Induced Regio‐ and Stereoselective Addition of Sulfenyl Chlorides to Alkynes by a Radical Pathway

The radical addition of the Cl? S σ‐bond in sulfenyl chlorides to various C? C triple bonds has been achieved with excellent regio‐ and stereoselectivity in the presence of a catalytic amount of a common iron salt. The reaction is compatible with a variety of functional groups and can be scaled up to the gram‐scale with no loss in yield. As well as terminal alkynes, internal alkynes underwent stereodefined chlorothiolation to provide tetrasubstituted alkynes. Preliminary mechanistic investigations revealed a plausible radical process involving a sulfur‐centered radical intermediate via iron‐mediated homolysis of the Cl? S bond. The resulting chlorothiolation adducts can be readily transformed to the structurally complex alkenyl sulfides by cross‐coupling reactions. The present reaction can also be applied to the complementary synthesis of the potentially useful bis‐sulfoxide ligands for transition‐metal‐catalyzed reactions.     

Regioselective Formation of (E)‐β‐Vinylstannanes with a Topologically Controlled Molybdenum‐Based Alkyne Hydrostannation Catalyst

The regioselective formation of (E)‐β‐vinylstannanes has been a long‐standing challenge in transition‐metal‐catalyzed alkyne hydrostannation. Herein, we report a well‐defined molybdenum‐based system featuring two encumbering m‐terphenyl isocyanides that reliably and efficiently delivers (E)‐β‐vinylstannanes from a range of terminal and internal alkynes with high regioselectivity. The system is particularly effective for aryl alkynes and can discriminate between alkyl chains of low steric hindrance in unsymmetrically substituted dialkyl alkynes. Catalytic hydrostannation with this system is also characterized by an electronic effect that leads to a decrease in regioselectivity when electron‐withdrawing groups are present on the alkyne substrate.     

Copper‐Catalyzed Synthesis of Alkynyl Hydrazones from Alkynes and Hydrazonyl Chlorides

A novel ligand‐free synthesis of alkynyl hydrazones via coupling reaction of hydrazonyl chlorides and terminal alkynes, catalyzed by CuI led to excellent yields.     

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.     

Z‐Selective (Cross‐)Dimerization of Terminal Alkynes Catalyzed by an Iron Complex

Efficient iron‐catalyzed homocoupling of terminal alkynes and cross‐dimerization of aryl acetylenes with trimethylsilylacetylene is reported. The complex [Fe(H)(BH₄)(iPr‐PNP)] ( 1 ) catalyzed the (cross‐)dimerization of alkynes at room temperature, with no need for a base or other additives, to give the corresponding dimerized products with Z selectivity in excellent yields (79–99 %).     

3 d Transition Metal‐Catalyzed Hydrogenation of Nitriles and Alkynes

Selective hydrogenation of nitriles and alkynes is crucial considering the vast applications of reduced products in industries and in the synthesis of bioactive compounds. Particularly, the late 3d transition metal catalysts (manganese, iron, cobalt, nickel and copper) have shown promising activity for the hydrogenation of nitriles to primary amines, secondary amines and imines. Similarly, semihydrogenation of alkynes to E‐ and Z‐alkenes by 3d metals is adequately successful both via the transfer hydrogenation and by using molecular hydrogen. The emergence of 3d transition metals in the selective synthesis of industrially relevant amines, imines and alkenes makes this protocol more attractive. Herein, we provide a concise overview on the late 3d transition metal‐catalyzed hydrogenation of nitriles to amines and imines as well as semihydrogenation of alkynes to alkenes.     

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.     

Organosulfide‐Catalyzed Diboration of Terminal Alkynes under Light

An efficient metal‐free diboration of terminal alkynes is reported. In the presence of a catalytic amount of organosulfides under light, the addition of bis(pinacolato)diboron (B₂pin₂) to terminal alkynes takes place efficiently to produce the corresponding double borylation products in good yields. Mechanistic studies indicate that this metal‐free sulfide‐catalyzed diboration of alkynes likely occurs by generation of a boryl‐centered radical with the aid of light and a sulfide, since such a radical was detected in the reaction mixture by electron spin resonance (ESR) spectroscopy. The present form of catalysis (sulfide/light) is thought to be unprecedented and provides a new means of preparation for organoboranes without heavy metal contamination in the products, which is highly desired in the preparation of drugs and electronic materials.     

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.     

Xantphos Doped POPs‐PPh3 as Heterogeneous Ligand for Cobalt‐Catalyzed Highly Regio‐ and Stereoselective Hydrosilylation of Alkynes

A Co(acac)₂/POL‐Xantphos@10PPh₃‐catalyzed hydrosilylation of unsymmetrical internal alkynes with Ph₂SiH₂ has been developed for the synthesis of highly selective syn‐α‐vinylsilane products. Furthermore, terminal alkynes were also used and gave the products with excellent regioselectivity and a wide functional group tolerance. Because this porous organic polymer combines the selectivity and activity merits of Xantphos with the stability advantage derived from the high concentration of PPh₃, the Co(acac)₂/POL‐Xantphos@10PPh₃ can be recycled multiple times without loss of activity and selectivity. This heterogeneous catalyst is expected to find promising applications in industrial synthesis.     

Highly Regioselective Sequential 1,1‐Dihydrosilylation of Terminal Aliphatic Alkynes with Primary Silanes

A regioselective double 1,1‐hydrosilylation of terminal aliphatic alkynes with primary silanes catalyzed by one cobalt catalyst has been developed. gem‐Bis(dihydrosilyl)alkanes containing four silicon‐hydrogen bonds are efficiently constructed in an atom‐economical manner. Tolerated substrates include simplest alkyne‐ethyne, a complicated drug derivative and various functionalized terminal aliphatic alkynes. Asymmetric approach using two catalysts is achieved with excellent enantioselectivities to access corresponding chiral products. The transformations of Si—H bonds into Si—C, Si—O, and Si—F bonds and the synthesis of enantioriched α‐hydroxysilane show synthetic utility.     

Room‐Temperature Arylation of Thiols: Breakthrough with Aryl Chlorides

The formation of aryl C−S bonds is an important chemical transformation because aryl sulfides are valuable building blocks for the synthesis of biologically and pharmaceutically active molecules and organic materials. Aryl sulfides have traditionally been synthesized through the transition‐metal‐catalyzed cross‐coupling of aryl halides with thiols. However, the aryl halides used are usually bromides and iodides; readily available, low‐cost aryl chlorides often not reactive enough. Furthermore, the deactivation of transition‐metal catalysts by thiols has forced chemists to use high catalyst loadings, specially designed ligands, high temperatures, and/or strong bases, thus leading to high costs and the incompatibility of some functional groups. Herein, we describe a simple and efficient visible‐light photoredox arylation of thiols with aryl halides at room temperature. More importantly, various aryl chlorides are also effective arylation reagents under the present conditions.     

Cu–N‐heterocyclic carbene‐catalysed synthesis of 2‐aryl‐3‐(arylethynyl)quinoxalines from one‐pot tandem coupling of o‐phenylenediamines and terminal alkynes

A series of new benzimidazolium chlorides bearing N,N′‐benzyl, 2,4,6‐trimethylbenzyl and 2,4,6‐triisopropylbenzyl substituents have been designed and synthesized from various o‐phenylenediamines. Subsequently, corresponding Cu‐based N‐heterocyclic carbenes (NHCs) were generated in situ in the reaction medium which represents a new application of NHCs exploiting distinct catalytic property towards intermolecular cyclization reaction cascade for the synthesis of 2‐aryl‐3‐(arylethynyl)quinoxalines from o‐phenylenediamines and terminal alkynes. The outcome of the cyclization reaction product depends upon the N,N′‐substituents present on the benzimidazolium chlorides.     

Ring‐Opening Regio‐, Diastereo‐, and Enantioselective 1,3‐Chlorochalcogenation of Cyclopropyl Carbaldehydes

meso‐Cyclopropyl carbaldehydes are treated in the presence of an organocatalyst with sulfenyl and selenyl chlorides to afford 1,3‐chlorochalcogenated products. The transformation is achieved by a merged iminium–enamine activation. The enantioselective desymmetrization reaction, leading to three adjacent stereocenters, furnished the target products in complete regioselectivity and moderate to high diastereo‐ and enantioselectivities (d.r. up to 15:1 and e.r. up to 93:7).     

Directing‐Group‐mediated C−H‐Alkynylations

C?C triple bonds are amongst the most versatile functional groups in synthetic chemistry. Complementary to the Sonogashira coupling the direct metal‐catalyzed alkynylation of C?H bonds has emerged as a highly promising approach in recent years. To guarantee a high regioselectivity suitable directing groups (DGs) are necessary to guide the transition metal (TM) into the right place. In this Focus Review we present the current developments in DG‐mediated C(sp²)?H and C(sp³)?H modifications with terminal alkynes under oxidative conditions and with electrophilic alkynylation reagents. We will discuss further modifications of the alkyne, in particular subsequent cyclizations to carbo‐ and heterocycles and modifications of the DG in the presence of the alkyne.     

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.     

Mechanism of Gold(I)‐Catalyzed Conia‐ene Reaction of β‐Ketoesters with Alkynes: A DFT Study

Density functional calculations have been performed to comparatively investigate two possible pathways of Au(I)‐catalyzed Conia‐ene reaction of β‐ketoesters with alkynes. Our studies find that, under the assistance of trifluoromethanesulfonate (TfO), the β‐ketoester is the most likely to undergo Model II to isomerize into its enol form, in which TfO plays a proton transfer role through a 6‐membered ring transition state. The coordination of the Au(I) catalyst to the alkynes triple bond can enhance the eletrophilic capability and reaction activity of the alkynes moiety, which triggers the nucleophilic addition of the enol moiety on the alkynes moiety to give a vinyl‐Au intermediate. This cycloisomerizaion step is exothermal by 21.3 kJ/mol with an energy barrier of 56.0 kJ/mol. In the whole catalytic process, the protonation of vinyl‐Au is almost spontaneous, and the formation of enol is a rate‐limiting step. The generation of enol and the activation of Au(I) catalyst on the alkynes are the key reasons why the Conia‐ene reaction can occur in mild condition. These calculations support that Au(I)‐catalyzed Conia‐ene reactions of β‐ketoesters with alkynes go through the pathway 2 proposed by Toste.     

Copper‐Catalyzed Tandem Synthesis of Functionalized Sulfonyl‐yn‐imines from Sodium Arylsulfinates,Trichloroacetonitrile, and Terminal Alkynes

A one‐pot synthesis of functionalized sulfonyl‐yn‐imines via a Cu‐catalyzed tandem reaction of sodium arylsulfinates, trichloroacetonitrile, and terminal alkynes has been developed.     

Platinum‐Catalyzed Asymmetric Ring‐opening Reaction of Oxabenzonorbornadiene with Terminal Alkynes

A novel platinum‐catalyzed asymmetric ring‐opening reaction of oxabenzonorbornadiene with terminal alkynes is described. The reaction affords optically active cis‐2‐alkynyl‐1,2‐dihydronaphthalen‐1‐ols in moderate yields with good enantioselectivity in the presence of catalytic amounts of Pt(COD)Cl₂/(S)‐BINAP and an excess of zinc powder. The products were obtained exclusively with the relative cis‐configuration of the ring substituents and the prevalent (1R,2S)‐configuration of the stereocenters, as determined by single crystal X‐ray diffraction analysis.     

Facile synthesis of 1, 2‐benzisothiazole‐3‐one‐1,1 ‐dioxide methylsulfonyl derivatives

An improved and general synthesis of saccharin methylthio and methylsulfone derivatives from chlorosubstituted saccharins is presented. A large‐scale procedure for preparation of chloro‐substituted saccharins was developed. Treatment of the saccharin chlorides with sodium thiomethoxide and t‐BuOK in DMF gave the saccharin methyl sulfides, which upon chromium(VI) oxide catalyzed oxidation with periodic acid afforded the corresponding saccharin methylsulfones in high yields.