Cobalt‐Catalyzed,Aminoquinoline‐Directed C(sp2)H Bond Alkenylation by Alkynes

A method for cobalt‐catalyzed, aminoquinoline‐ and picolinamide‐directed C(sp²)? H bond alkenylation by alkynes was developed. The method shows excellent functional‐group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂?4 H₂O catalyst, Mn(OAc)₂ co‐catalyst, and oxygen (from air) as a terminal oxidant.     

Mapping the Interactions of I2, I., I−, and I+ with Alkynes and Their Roles in Iodocyclizations

A combination of experiment and theory has been used to explore the mechanisms by which molecular iodine (I₂) and iodonium ions (I⁺) activate alkynes towards iodocyclization. Also included in the analysis are the roles of atomic iodine (I ^. ) and iodide ion (I^?) in mediating the competing addition of I₂ to the alkyne. These studies show that I₂ forms a bridged I₂–alkyne complex, in which both alkyne carbons are activated towards nucleophilic attack, even for quite polarized alkynes. By contrast, I⁺ gives unsymmetrical, open iodovinyl cations, in which only one carbon is activated toward nucleophilic attack, especially for polarized alkynes. Addition of I₂ to alkynes competes with iodocyclization, but is reversible. This fact, together with the capacity of I₂ to activate both alkyne carbons towards nucleophilic attack, makes I₂ the reagent of choice (superior to iodonium reagents) for iodocyclizations of resistant substrates. The differences in the nature of the activated intermediate formed with I₂ versus I⁺ can also be exploited to accomplish reagent‐controlled 5‐exo/6‐endo‐divergent iodocyclizations.     

A Convergent Synthesis of Functionalized Alkenyl Halides through Cobalt(III)‐Catalyzed Three‐Component C−H Bond Addition

A Co^III‐catalyzed three‐component coupling of C(sp²)−H bonds, alkynes, and halogenating agents to give alkenyl halides is reported. This transformation proceeds with high regio‐ and diastereoselectivity, and is effective for a broad range of aryl and alkyl terminal alkynes. Diverse C−H bond partners also exhibit good reactivity for a range of heteroaryl and aryl systems as well as synthetically useful secondary and tertiary amide, urea, and pyrazole directing groups. This multicomponent transformation is also compatible with allenes in place of alkynes to furnish tetrasubstituted alkenyl halides, showcasing the first halo‐arylation of allenes.     

Cobalt‐Catalyzed,Aminoquinoline‐Directed C(sp2)?H Bond Alkenylation by Alkynes

A method for cobalt‐catalyzed, aminoquinoline‐ and picolinamide‐directed C(sp²) H bond alkenylation by alkynes was developed. The method shows excellent functional‐group tolerance and both internal and terminal alkynes are competent substrates for the coupling. The reaction employs a Co(OAc)₂⋅4 H₂O catalyst, Mn(OAc)₂ co‐catalyst, and oxygen (from air) as a terminal oxidant.     

Nickel‐Catalyzed Insertion of Alkynes and Electron‐Deficient Olefins into Unactivated sp3 CH Bonds

Insertion of unsaturated systems such as alkynes and olefins into unactivated sp³ C?H bonds remains an unexplored problem. We herein address this issue by successfully incorporating a wide variety of functionalized alkynes and electron‐deficient olefins into the unactivated sp³ C?H bond of pivalic acid derivatives with excellent syn‐ and linear‐ selectivity. A strongly chelating 8‐aminoquinoline directing group proved beneficial for these insertion reactions, while an air‐stable and inexpensive Ni^II salt has been employed as the active catalyst.     

Synthesis and spectroscopic characteristics of σ-vinyl derivatives of platinum(<Emphasis Type="SmallCaps">IV</Emphasis>) chloride complexes

A procedure was developed for the synthesis of previously unknown β-chlorovinyl derivatives of Pt^IV chloride complexes by chloroplatination of terminal alkynes catalyzed by Pt^II chloride complexes. The reaction is highly stereoselective and gives only the products of trans-anti-addition of platinum and chlorine atoms. The regioselectivity of the catalytic reaction formally corresponds to Markovnikov’s rule, e.g., in alkynes containing electron-donating substituents, platinum attacks the terminal carbon atom. The σ-vinyl derivatives of Pt^IV chloride complexes were characterized by IR spectroscopy and ¹H and ¹³C NMR spectroscopy. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2380–2384, October, 2005.     

A Sequential Homologation of Alkynes and Aldehydes for Chain Elongation with Optional 13C‐Labeling

Terminal alkynes (RCCH) are homologated by a sequence of ruthenium‐catalyzed anti‐Markovnikov hydration of alkyne to aldehyde (RCH₂CHO), followed by Bestmann–Ohira alkynylation of aldehyde to chain‐elongated alkyne (RCH₂CCH). Inverting the sequence by starting from aldehyde brings about the reciprocal homologation of aldehydes instead. The use of ¹³C‐labeled Bestmann–Ohira reagent (dimethyl ((1‐¹³C)‐1‐diazo‐2‐oxopropyl)phosphonate) for alkynylation provides straightforward access to singly or, through additional homologation, multiply ¹³C‐labeled alkynes. The labeled alkynes serve as synthetic platform for accessing a multitude of specifically ¹³C‐labeled products. Terminal alkynes with one or two ¹³C‐labels in the alkyne unit have been submitted to alkyne–azide click reactions; the copper‐catalyzed version (CuAAC) was found to display a regioselectivity of >50 000:1 for the 1,4‐ over the 1,5‐triazine isomer, as shown analytically by ¹³C NMR spectroscopy.     

Synthesis of New 1,2,3‐Triazole Derivatives Possessing 4H‐Pyran‐4‐one Moiety by 1,3‐Dipolar Cycloaddition Reaction of Azidomethyl Phenylpyrone with Various Alkynes

A series of new 1,2,3‐triazole derivatives were synthesized by 1,3‐dipolar cycloaddition reaction of 2‐(4‐azidomethylphenyl)‐6‐phenyl‐4H‐pyran‐4‐one with different alkynes in 40–71% yields. In the case of terminal alkynes, the reaction was proceeded in the presence of Cu(I) catalyst. The structure of the synthesized compounds were confirmed by FTIR, ¹H‐NMR, and ¹³C‐NMR spectroscopy and elemental analysis.     

3‐(Diphenylphosphino)propanoic acid: an efficient ligand for the Pd/Cu‐catalyzed homo‐coupling of terminal alkynes in the presence of oxygen at room temperature

A simple, yet efficient system for PdCl₂/CuI to catalyze the homo‐coupling reactions of various terminal alkynes has been developed using 3‐(diphenylphosphino)propanoic acid as ligand in the presence of oxygen. The alkynes, including aromatic, heteroaromatic and aliphatic alkynes, were transformed at room temperature into the corresponding 1,3‐diynes in moderate to excellent yields. The turnover number was up to 1.04 × 10³. Copyright © 2015 John Wiley & Sons, Ltd.     

Palladium‐Catalyzed One‐Pot Three‐ or Four‐Component Coupling of Aryl Iodides,Alkynes, and Amines through CN Bond Cleavage: Efficient Synthesis of Indole Derivatives

An efficient synthesis of N‐substituted indole derivatives was realized by combining the Pd‐catalyzed one‐pot multicomponent coupling approach with cleavage of the C(sp³)?N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene–phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1‐bromo‐2‐iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4‐methylpiperidine, 1‐methylpiperazine, 2‐methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3‐b]indole.     

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.     

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.     

2,4‐Dinitrophenol‐Catalyzed α‐C(sp3)−H and C(sp)−H Bond Functionalization of Cyclic Amines and Alkynes: Highly Regio‐/Diastereoselective Synthesis of α‐Alkynyl‐3‐Amino‐2‐Oxindoles

A transition‐metal‐ and oxidant‐free DNP (2,4‐dinitrophenol)‐catalyzed atom‐economical regio‐ and diastereoselective synthesis of monofunctionalized α‐alkynyl‐3‐amino‐2‐oxindole derivatives by C?H bond functionalization of cyclic amines and alkynes with indoline‐2,3‐diones has been developed. This cascade event sequentially involves the reductive amination of indoline‐2,3‐dione by imine formation and cross coupling between C(sp³)?H and C(sp)?H of the cyclic amines and alkynes. This reaction offers an efficient and attractive pathway to different types of α‐alkynyl‐3‐amino‐2‐oxindole derivatives in good yields with a wide tolerance of functional groups. The salient feature of this methodology is that it completely suppresses the homocoupling of alkynes. To the best of our knowledge, this is the first example of a DNP‐catalyzed metal‐free direct C(sp³)?H and C(sp)?H bond functionalization providing biologically active α‐alkynyl‐3‐amino‐2‐oxindole scaffolds.     

Gold‐Catalyzed C(sp3)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

In sharp contrast to the gold‐catalyzed reactions of alkynes/allenes with nucleophiles, gold‐catalyzed oxidative cross‐couplings and especially C? H/C? H cross‐coupling have been under represented. By taking advantage of the unique redox property and carbophilic π acidity of gold, this work realizes the first gold‐catalyzed direct C(sp³)? H alkynylation of 1,3‐dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region‐defined approach to 3‐alkynyl polysubstituted furans.     

Microwave‐Assisted,Rhodium(III)‐Catalyzed N‐Annulation Reactions of Aryl and α,β‐Unsaturated Ketones with Alkynes

New Rh^III‐catalyzed, one‐pot N‐annulation reactions of aryl and α,β‐unsaturated ketones with alkynes in the presence of ammonium acetate have been developed. Under microwave irradiation conditions, the processes lead to rapid formation of the respective isoquinoline and pyridine derivatives with efficiencies that are strongly dependent on the steric nature of the aryl ring and enone substituents. By employing this protocol, a variety of isoquinoline and pyridine derivatives were prepared in high yields. In addition, a new one‐pot approach to the synthesis of pyridines, involving four‐component reactions of ketones, formaldehyde, NH₄OAc, and alkynes, has been uncovered. This process takes place through a route involving initial aldol condensation of the ketone with formaldehyde to generate a branched α,β‐unsaturated ketone that then undergoes Rh^III‐catalyzed N‐annulation with NH₄OAc and the alkyne.     

Key Non‐Metal Ingredients for Cu‐catalyzed “Click” Reactions in Glycerol: Nanoparticles as Efficient Forwarders

The effect of long‐alkyl‐chain amines in CuI‐assisted azide–alkyne cycloadditions of terminal alkynes with organic azides in glycerol and other environmentally benign solvents (water, ethanol) has been examined. The presence of these additives favors the in situ formation of Cu^I‐based nanoparticles and results in an increase of the catalytic reactivity. In glycerol, liquid‐phase transmission electron microscopy (TEM) analyses, enabled by the negligible vapor pressure of this solvent, proved that Cu^I nanoparticles are responsible for the observed catalytic activity. The wide variety of alkynes and azides of which this effect has been investigated (14 combinations) confirms the role played by these additives in Cu‐catalyzed Huisgen cycloadditions.     

Nickel-catalyzed C–O/N–H,C–S/N–H,and C–CN/N–H annulation of aromatic amides with alkynes: C–O,C–S,and C–CN activation

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones. The use of a base is essential for the reaction to proceed. The reaction proceeds, even in the absence of a ligand, and under mild reaction conditions (40 °C). An electron-donating group on the aromatic ring facilitates the reaction. The reaction was also applicable to carbamate (C–O bond activation), methylthio (C–S bond activation), and cyano (C–CN bond activation) groups as leaving groups.

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones.     

Decarboxylative A3‐coupling reactions: An overview

The propargylamine motif is not only prevalent in a wide variety of pharmaceuticals and other biologically active compounds but also utilized as a versatile building block in organic synthesis. Among the various methods for the synthesis of propargylamine derivatives, A³‐coupling represents one of the most general and attractive routes, since it offers the possibility for the construction of complex molecules from simple starting materials (amines, aldehydes, and alkynes) in one‐step with high atom economy. However, the use of volatile alkynes is the main disadvantage of this reaction. Recently, alkynyl carboxylic acids were successfully used as easily accessible and high stable surrogates for alkynes (via in situ decarboxylation) in A³‐coupling reactions. This Focus‐Review aims to give an overview of the decarboxylative A³‐coupling reactions by hoping that it will be beneficial to elicit further research in this appealing research arena. A special emphasis is placed on mechanistic aspect of reactions which may allow possible new insights into catalyst improvement.     

Strain‐Accelerated Formation of Chiral,Optically Active Buta‐1,3‐dienes

The formal [2+2] cycloaddition–retroelectrocyclization (CA–RE) reactions between tetracyanoethylene (TCNE) and strained, electron‐rich dibenzo‐fused cyclooctynes were studied. The effect of ring strain on the reaction kinetics was quantified, revealing that the rates of cycloaddition using strained, cyclic alkynes are up to 5500 times greater at 298 K than those of reactions using unstrained alkynes. Cyclobutene reaction intermediates, as well as buta‐1,3‐diene products, were isolated and their structures were studied crystallographically. Isolation of a rare example of a chiral buta‐1,3‐diene that is optically active and configurationally stable at room temperature is reported. Computational studies on the enantiomerization pathway of the buta‐1,3‐diene products showed that the eight‐membered ring inverts via a boat conformer in a ring‐flip mechanism. In agreement with computed values, experimentally measured activation barriers of racemization in these compounds were found to be up to 26 kcal mol^?1.     

Rhodium(III)‐Catalyzed CC and CO Coupling of Quinoline N‐Oxides with Alkynes: Combination of CH Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C? H activation of arenes assisted by an oxidizing N? O or N? N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N? O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N? O bonds in both C? H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N? O bond acts as both a directing group for C? H activation and as an O‐atom donor.