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Inexpensive cobalt‐catalyzed, pivalic acid‐assisted oxidative C−H functionalization of benzimidates or NH‐benzaldimines with ynamides is presented, providing an access to 3‐aminoisoquinoline derivatives. The procedure is compatible with various substrates featuring alkyl, alkoxy, acyl or halogen as substituents, heteroaryl structures, and diverse ynamides. The reaction has been scaled up, with subsequent transformation of the yielded products. Control experiments and mechanistic investigations corroborate the regioselectivity of this conversion, positioning the amine group proximal to the nitrogen atom in isoquinolines. [ABSTRACT FROM AUTHOR]

In this manuscript we report the synthesis of 3‐amido‐benzo[b]silines thanks to a 2‐step strategy involving a 3‐component silylformylation of ynamides followed by a Friedel‐Crafts cyclization/isomerizing dehydration domino sequence. This reaction is tolerant to various structural variations and has allowed us to synthesize a library of diversely substituted silacycles with yields from 33 to 85%. We also studied the fluorescence properties of these compounds which show structural similarities with recognized probes such as Si‐Rhodamine for example. [ABSTRACT FROM AUTHOR]

We report here a formal insertion of a metal carbene complex in a single carbon‐carbon bond. This behavior occurs with the participation of an α‐imino gold carbene complex, generated from benzofused triazapentalenes or, in a one‐pot procedure, from their 1‐propargyl‐1H‐benzotriazole precursors, and gold‐catalytically activated ynamides. As the result, 3H‐indole derivatives were obtained, with formation of a quaternary center. A computational analysis carried out on the reaction mechanism indicates that the bulkiness of the gold ligand plays a key role forcing a conformation, which includes aromatic interactions, that favors the approximation of the carbenic carbon to the reactive site. In addition, a negative crossover experiment rules out a cationic arene migration pathway. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of ynamides, a class of N-alkynyl compounds, through various catalytic reactions. The authors highlight the importance of ynamides in the synthesis of nitrogen-containing scaffolds and summarize existing methods for their synthesis. They also present their own research on the direct catalytic addition of terminal alkynes to azodicarboxylates to produce ynehydrazides, which can then be converted into ynamides. The authors propose potential future directions for further research in this field. [Extracted from the article]

This article discusses a new method for synthesizing β-acylamino amides, which are important compounds found in natural products, β-peptides, and pharmaceuticals. The traditional method for synthesizing these compounds is limited and uses hazardous components. However, the authors propose a more efficient approach using multicomponent reactions (MCRs) with Lewis acids and temperature modification strategies. The article describes the reaction conditions, optimization, and substrate scope, and proposes a reaction mechanism based on experimental results. This method provides a practical and efficient approach to synthesizing amino amides with a branched aliphatic chain, which is important in medicinal chemistry. [Extracted from the article]

Environmentally friendly acid-catalyzed ynamide N–Csp bond cleavage, skeletal rearrangement and chemo-, regio- and stereospecific functionalization with nucleophiles are of great interest in synthetic chemistry. However, such transformations present remarkable regio- and stereospecific challenges due to the biased carbon–carbon (α and β) triple bonds in ynamides. Herein, we developed a greener and faster acid-catalyzed ynamide N–Csp bond fission, skeletal rearrangement and stereospecific functionalization with nucleophilic anisole derivatives to produce thermodynamically unstable challenging cis-alkene tethered indole scaffolds in a very short reaction time (5–10 min). The key features of this transformation are its transition-metal-free nature, broad scope, ease of handling, simple setup, mild reaction conditions, atom/step/time economy, and the gram-scale experiment. Most importantly, 13C-isotope labeling experiments in mechanistic studies confirmed the alkyne-carbon position in the rearrangement process. The green chemistry metrics evaluation and EcoScale score (75 on a scale of 0–100) indicate that our transformation is safer, environmentally friendly, and economically feasible. [ABSTRACT FROM AUTHOR]

The hydrofluorination of alkynes is an efficient synthetic route to monofluoroalkenes or difluoroalkanes. Both fluorinated motifs have found applications in medicinal chemistry and beyond. This review explores the recent advances in the hydrofluorination of diverse alkynes through various activation methods, from classical coinage metal catalysis to metal‐free conditions. The range of alkynes goes from the simplest unactivated alkynes to activated ones (ynones and derivatives, ynamides, alkynyl sulfides and sulfones as much as haloalkynes). Regio‐ and stereoselective methods exists, but there is still room for improvement depending on the type of alkyne. [ABSTRACT FROM AUTHOR]

N-Arenesulfonyl α-hydroxyamides are conveniently synthesized from N-arylethynylsulfonamides (ynamides) via oxidation with dimethyl sulfoxide (DMSO) in the presence of equivalent of trifluoromethanesulfonic acid (TfOH) followed by treatment with water. In this reaction, ynamides are activated by protonation with TfOH and then undergo double DMSO nucleophilic addition and subsequent hydrolysis. Investigations on the substrate scope indicate N-arenesulfonyl and arylethynyl substituted ynamides proceed the oxidation well. Compared to the previous methods, the current method realizes the direct conversion from N-arylethynylsulfonamides to N-arenesulfonyl α-hydroxyamides with mild DMSO as a nucleophilic oxidant in the presence of strong acid trifluoromethanesulfonic acid. [ABSTRACT FROM AUTHOR]

First examples of the reactions of 3-trimethylsilyl-2-propynamides with organic diselenides yielding 3-alkylselanyl-2-propenamides and 3-organylselanyl-2-propynamides were realized. The latter compounds were obtained by the Cu-catalyzed reaction of organic diselenides with 4-propioloylmorpholine. The reaction of 3-trimethylsilyl-2-propynamides with dialkyl diselenides in the system NaBH4/H2O/K2CO3/THF proceeded in a regio- and stereoselective fashion, affording 3-alkylselanyl-2-propenamides in 90–94% yields. An unsymmetrical divinyl selenide with the cyclic amide groups and a product, containing two selanyl-2-propenamide moieties and three cyclic amide groups, were synthesized. The Cu-catalyzed allylation reaction of 3-trimethylsilyl-2-propynamides was accompanied with desilylation to yield 3-allyl-2-propynamides. [ABSTRACT FROM AUTHOR]

We demonstrate the potential of Ni(COD)(DQ), a bench-stable Ni0 complex, as a catalyst for the reductive coupling of aldehydes with alkynes and ynamides, providing silylated allyl alcohols with excellent yields and regioselectivities. Mass spectrometric identification of the intermediates and DFT studies supported the proposed mechanism. [ABSTRACT FROM AUTHOR]

An efficient approach to a novel family of (Z)-3-amino-3-oxo-1-propenyl selenocyanates was developed based on the reaction of KSeCN with 3-trimethylsilyl-2-propynamides in the presence of ammonium chloride in methanol. The reaction was accompanied by a desilylation process. The products were not formed under the same reaction conditions in the absence of ammonium chloride, which was used for the first time in the reactions of selenocyanates with acetylenes. The use of this new methodology allowed the reaction to carry out in a regio- and stereoselective fashion as anti-addition affording vinyl selenocyanates with a (Z)-configuration in high yields. [ABSTRACT FROM AUTHOR]

Ynamides/arylynamines are challenging substrates for oxyacetoxylation, especially due to various reactive sites of the N‐heteroaryl ring. Herein, we report a metal‐free PhI(OAc)2‐mediated oxyacetoxylation of arylynamines/ynamides to provide α‐acetoxyl amides in good to excellent yields. The transformation completes in a short time to afford solely the product in a highly regio‐ and chemo‐selective manner through β‐iodo keteneiminium intermediate, without functionalising the N‐heteroaryl moiety. [ABSTRACT FROM AUTHOR]

Silver‐catalyzed N‐aryl‐1H‐pyrazolyl substituted benzenesulfonamide derivatives were obtained regioselectively from ynamides and pyrazoles. In this intermolecular organic transformation, several substituted benzenesulfonamides were obtained in good to excellent yields by forming a new C−N bond under mild reaction conditions. [ABSTRACT FROM AUTHOR]

The use of ynamides in organic synthesis has gained significant attention due to their ability to provide access to complex molecular structures through transformations such as 1,2‐difunctionalization and annulation reactions. These reactions enable the formation of highly functionalized N‐bearing olefins and unusual N‐bearing heterocycles. In this minireview, we present a systematic overview of the regioselective difunctionalization and annulation reactions of ynamides. We discuss the multi‐component reactions, and radical‐triggered functionalizations across the ynamides carbon–carbon multiple bonds and the use of bifunctional reagents in annulation of ynamides, highlighting their potential in expanding the substrate scope. Furthermore, we provide insights into the mechanistic breakthroughs that have been achieved in recent years in the development of these reactions. Finally, we emphasize the promising future prospects of ynamides as versatile building blocks for the synthesis of complex molecular architectures. [ABSTRACT FROM AUTHOR]

The use of ynamides in organic synthesis has gained significant attention due to their ability to provide access to complex molecular structures through transformations such as 1,2‐difunctionalization and annulation reactions. These reactions enable the formation of highly functionalized N‐bearing olefins and unusual N‐bearing heterocycles. In this minireview, we present a systematic overview of the regioselective difunctionalization and annulation reactions of ynamides. We discuss the multi‐component reactions, and radical‐triggered functionalizations across the ynamides carbon–carbon multiple bonds and the use of bifunctional reagents in annulation of ynamides, highlighting their potential in expanding the substrate scope. Furthermore, we provide insights into the mechanistic breakthroughs that have been achieved in recent years in the development of these reactions. Finally, we emphasize the promising future prospects of ynamides as versatile building blocks for the synthesis of complex molecular architectures. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed interplay between ynamides and aminocarbonyls comprises a route to 2‐aminoquinolines. This modular annulation proceeds under relatively mild conditions (Ph3PAuCl/AgNTf2 5 mol %, DCE, 60–80 °C), and a number of functionalities were compatible (42 examples; 25–98% yields). In contrast to a group of other gold‐catalyzed methods employing the ynamide/amine combinations for the assembly of 2‐aminoquinolines, the developed approach utilizes a diversity of aminocarbonyl substrates and, in particular, allows a variation of the substituents in the 4th quinoline position. The synthetic potential of the obtained heterocyclic products was illustrated by post‐modifications of the quinoline backbone and the peripheral substituents. [ABSTRACT FROM AUTHOR]

The first synthesis of N-(acyloxy)ynamides was realized through the coupling of N-(acyloxy)amides and hypervalent alkynyliodane under mild conditions. This reaction probably involves biradical species ("C2") generation and radical processes. Furthermore, we also demonstrated that N-(acyloxy)ynamide could be transformed into a N-sulfonylimidate derivative by a copper catalyst. This study provides new building blocks for synthetic organic chemistry reactions and improves understanding of the chemical reactivity of "C2". [ABSTRACT FROM AUTHOR]

Transition metal‐catalyzed divergent synthesis through alternation of the catalyst is appealing, as it provides an operationally simple way to access different valuable products, while using the same reactants as starting materials. Herein, a gold‐catalyzed cascade reaction of conjugated diynamides with allylic alcohols is described. By variation of the catalysts, substituted allenes and furans could be obtained selectively. Mechanistic studies indicate that, after the addition of allylic alcohol to gold‐activated diynamide, a [3,3]‐sigmatropic rearrangement would take place and lead to the formation of a common reactive intermediate, which would further convert to the final products selectively. Further variation of the structure of diynamides has unveiled an additional reaction sequence involving intramolecular Himbert arene/allene Diels‐Alder cycloaddition to afford a series of dearomatized products bearing bicyclo[2,2,2]octadiene core. [ABSTRACT FROM AUTHOR]

1,3-butadiynamides—the ethynylogous variants of ynamides—receive considerable attention as precursors of complex molecular scaffolds for organic and heterocyclic chemistry. The synthetic potential of these C4-building blocks reveals itself in sophisticated transition-metal catalyzed annulation reactions and in metal-free or silver-mediated HDDA (Hexa-dehydro-Diels–Alder) cycloadditions. 1,3-Butadiynamides also gain significance as optoelectronic materials and in less explored views on their unique helical twisted frontier molecular orbitals (Hel-FMOs). The present account summarizes different methodologies for the synthesis of 1,3-butadiynamides followed by the description of their molecular structure and electronic properties. Finally, the surprisingly rich chemistry of 1,3-butadiynamides as versatile C4-building blocks in heterocyclic chemistry is reviewed by compiling their exciting reactivity, specificity and opportunities for organic synthesis. Besides chemical transformations and use in synthesis, a focus is set on the mechanistic understanding of the chemistry of 1,3-butadiynamides—suggesting that 1,3-butadiynamides are not just simple alkynes. These ethynylogous variants of ynamides have their own molecular character and chemical reactivity and reflect a new class of remarkably useful compounds. [ABSTRACT FROM AUTHOR]

Triterpenoid natural products from the Schisandraceae family have long presented a significant synthetic challenge. Lancifodilactone I, a member of the family not previously synthesized, was identified as a key natural product target, from which many other members could be synthesized. We envisaged that the core ring system of lancifodilactone I could be accessed by a strategy involving palladium-catalysed cascade cyclisation of a bromoenynamide, via carbopalladation, Suzuki coupling and 8π-electrocyclisation, to synthesize the core 7,8-fused ring system. Exploration of this strategy on model systems resulted in efficient syntheses of 5,6- and 5,8-fused systems in high yields, which represent the first such cyclisation where the ynamide nitrogen atom is 'external' to the forming ring system. The enamide functionality resident in the cascade cyclisation product was found to be less nucleophilic than the accompanying tri-/tetrasubstituted alkene(s), enabling regioselective oxidations. Application of this strategy to 7,6-, and 7,8-fused systems, and ultimately the 'real' substrate, was ultimately thwarted by the difficulty of 7-membered ring closure, leading to side product formation. Nevertheless, a tandem bromoenynamide carbopalladation, Suzuki coupling and 6/8π-electrocyclisation was shown to be a highly efficient tactic for the formation of bicyclic enamides, which may find applications in other synthetic contexts. [ABSTRACT FROM AUTHOR]

The fully regio‐ and stereoselective Zn‐catalyzed hydrocyanation of ynamides is reported and represents a general access to various trisubstituted E‐α‐enamidonitriles. The catalyst‐free photoisomerization selectively yields the energetically comparable Z‐stereoisomer. Finally, the synthetic potential of these new α‐enamidonitriles was evaluated through the synthesis of original heterocycles. [ABSTRACT FROM AUTHOR]

We synthesized tetrasubstituted olefins regioselectively and stereoselectively from ynamides and internal alkynes with sulfonyl iodides under blue LEDs in few minutes. The key features are being metal-free, easy to handle, simple, broad in scope, and environmentally friendly. Furthermore, a gram-scale experiment was conducted, and the synthesized corresponding sulfonyl-iodinated products were smoothly altered into various other products. [ABSTRACT FROM AUTHOR]

We report herein intramolecular (3+2) cycloaddition reactions between ynamides as three‐atom components and benzyne. In these intramolecular reactions, the two‐bond formation is realized by exploiting benzyne precursors that contain a chlorosilyl group as a linking functionality. This method thus highlights the ambivalent character of the intermediate indolium ylide, which exhibits both nucleophilic and electrophilic properties at its C2 atom. [ABSTRACT FROM AUTHOR]

We report herein intramolecular (3+2) cycloaddition reactions between ynamides as three‐atom components and benzyne. In these intramolecular reactions, the two‐bond formation is realized by exploiting benzyne precursors that contain a chlorosilyl group as a linking functionality. This method thus highlights the ambivalent character of the intermediate indolium ylide, which exhibits both nucleophilic and electrophilic properties at its C2 atom. [ABSTRACT FROM AUTHOR]

The synthesis of 2‐aminopyrrolo[1,2‐b]pyridazines from 1,3‐diynamides and 1‐aminopyrroles via gold(I)‐catalyzed chemoselective hydroamination/hydroarylation cascade was described. 26 examples were conducted to explore the scope of the substrates. A plausible reaction mechanism was also proposed. In addition, the fluorescence properties both in solutions and in the solid states of the resulting products were investigated. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed three‐component syn‐1,2‐arylmethylation of internal alkynes (ynamides/yne‐acetates/alkynes) is described. The readily available and bench stable coupling partners iodo‐arenes, and methyl boronic acid are successfully used in this coupling strategy to access the methyl‐containing tetra‐substituted olefins; the scope is broad showing excellent functional‐group tolerance. Notably, the transformation is regio‐ as well as stereoselective. The biologically relevant motifs (BRM) bearing iodo‐arenes and ynamides are also used for the late‐stage syn‐1,2‐arylmethylation of alkynes. Aryl‐alkylation, aryl‐trideuteriomethylation, alkynyl‐methylation, and alkenyl‐methylation of ynamides are also presented. The Me‐substituted alkenes are further transformed into synthetically important β‐amino‐indenones and α‐fluoro‐α′‐methyl ketones. [ABSTRACT FROM AUTHOR]

A Pd‐catalyzed three‐component syn‐1,2‐arylmethylation of internal alkynes (ynamides/yne‐acetates/alkynes) is described. The readily available and bench stable coupling partners iodo‐arenes, and methyl boronic acid are successfully used in this coupling strategy to access the methyl‐containing tetra‐substituted olefins; the scope is broad showing excellent functional‐group tolerance. Notably, the transformation is regio‐ as well as stereoselective. The biologically relevant motifs (BRM) bearing iodo‐arenes and ynamides are also used for the late‐stage syn‐1,2‐arylmethylation of alkynes. Aryl‐alkylation, aryl‐trideuteriomethylation, alkynyl‐methylation, and alkenyl‐methylation of ynamides are also presented. The Me‐substituted alkenes are further transformed into synthetically important β‐amino‐indenones and α‐fluoro‐α′‐methyl ketones. [ABSTRACT FROM AUTHOR]

A triphenylphosphine‐ligated cobalt‐catalyzed cyclization manifold with various 1,3‐dicarbonyl compounds and halogenated N‐allyl ynamides was accomplished under alkaline reaction conditions, facilitating the synthesis of differently sized N‐heterocycles. A large array of products was prepared to demonstrate the selective synthesis of N‐heterocycles of different ring sizes (5‐, 6‐, and 7‐membered rings) via cobalt catalysis. The reaction has broad substrate scope and a wide range of functional groups. [ABSTRACT FROM AUTHOR]

Herein, an I2‐catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom‐economy. This protocol not only represents the first molecular‐iodine‐catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine‐ynamides involving distinctively different C(sp3)−C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5‐exo‐dig cyclization/rearrangement process. [ABSTRACT FROM AUTHOR]

Herein, an I2‐catalyzed unprecedented cycloisomerization of ynamides is developed, furnishing various functionalized bis(indole) derivatives in generally good to excellent yields with wide substrate scope and excellent atom‐economy. This protocol not only represents the first molecular‐iodine‐catalyzed tandem complex alkyne cycloisomerizations, but also constitutes the first chemoselective cycloisomerization of tryptamine‐ynamides involving distinctively different C(sp3)−C(sp3) bond cleavage and rearrangement. Moreover, chiral tetrahydropyridine frameworks containing two stereocenters are obtained with moderate to excellent diastereoselectivities and excellent enantioselectivities. Meanwhile, cycloisomerization and aromatization of ynamides produce pyrrolyl indoles with high efficiency enabled by I2. Additionally, control experiments and theoretical calculations reveal that this reaction probably undergoes a tandem 5‐exo‐dig cyclization/rearrangement process. [ABSTRACT FROM AUTHOR]

Nickel(0) nanoparticles coordinated to NHC ligands bearing N-coordinated cinnamyl moieties were readily prepared by reduction of a [NiCpBr(NHC-cinnamyl)] complex with methyl magnesium bromide. The combination of a strong σ-donor NHC ligand with a π-coordinating appended cinnamyl moiety likely prevents nickel(0) nanoparticle aggregation to larger inactive species, and allows the effective and (Z)-selective semi-hydrogenation of alkynes and ynamides. [ABSTRACT FROM AUTHOR]

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold‐catalyzed and para‐toluenesulfonic acid (PTSA)‐assisted cascade cycloisomerization reaction for the synthesis of β‐pyrrole substituted α,β‐unsaturated ketones. Notably, the reaction is stereoselective, offering E‐isomer as major product with low to moderate yield. [ABSTRACT FROM AUTHOR]

A new mesoporous MCM-41-immobilized dichloro(pyridine-2-carboxylato)gold(III) complex [MCM-41-PicAuCl2] was synthesized via an addition reaction of a dichloro(3-hydroxypyridine-2-carboxylato)gold(III) complex to triethoxy(3-isocyanatopropyl)silane, followed by immobilization on MCM-41 and was characterized by different physico-chemical techniques. In the presence of 5 mol% of MCM-41-PicAuCl2, the annulation reaction between anthranils and ynamides proceeded smoothly under mild conditions to afford diverse 6- or 5-formylindoles with high atom economy and good to excellent yields. This new heterogenized gold(III) complex can be easily recovered through a simple filtration process and recycled more than seven times without any apparent loss of its catalytic efficiency. [ABSTRACT FROM AUTHOR]

An efficient radical cyclization of suitably functionalized ynamides to nitrogen-containing heterocycles is reported. Upon reaction with tributyltin hydride in the presence of catalytic amounts of AIBN in toluene at 80 °C, a range of ynamides bearing a N -iodopropyl chain could be smoothly cyclized, in a highly regio- and stereoselective manner, to the corresponding 2-arylidenepyrrolidines in good to excellent yields. The exocyclic double bond was in addition shown to be an excellent anchor for further chemical diversification and the generality of this radical cyclization could be highlighted by its extension to the synthesis of other nitrogen heterocycles including piperidines, azepanes, pyrazolidines and hexahydropyridazines. [ABSTRACT FROM AUTHOR]

A late-stage diversification strategy for synthesizing ynamides has been developed. This strategy was enabled by the copper-catalyzed direct electrophilic diynylation of sulfonamides with a novel triisopropylsilyl diynyl benziodoxolone, deprotection, and the late-stage chemoselective copper-catalyzed azide–alkyne cycloaddition sequence, which yields various complex molecule-derived ynamides with pyrene, amino acid, nucleoside, and N-acetylglucosamine as substituents. [ABSTRACT FROM AUTHOR]

α‐Amino acid derivatives are key components of the molecules of life. The synthesis of α‐amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we report a practical method for the preparation of α‐amino acid derivatives via direct hydrative amination of activated alkynes under mild conditions, relying on sulfinamides as the nitrogen source. Computational studies suggest that the reaction is enabled by a new type of sulfonium [2,3]‐sigmatropic rearrangement. [ABSTRACT FROM AUTHOR]

The aim of this Short Review is to give an updated overview of the synthesis of α-haloenamides, which constitute a versatile subclass of enamides. α-Haloenamides can be prepared from ynamides, acetamides, or gem -dibromoalkenes in the presence of N -nucleophiles and easily converted into more elaborated structures through halogen-metal exchange and transition-metal-catalyzed cross-coupling reactions. 1 Introduction 2 α-Haloenamide Synthesis 2.1 Hydrohalogenation of Ynamides 2.1.1 cis -Hydrohalogenation of Ynamides 2.1.2 trans -Hydrohalogenation of Ynamides 2.2 α,β-Dihalogenation 2.2.1 lodochlorination and Iodobromination of Ynamides 2.2.2 Iodofluorination of Ynamides 2.3 Chloroselenation of Ynamides 2.4 Carbohalogenation of Ynamides 2.4.1 Carboiodination 2.4.2 Chloroallylation 2.4.3 Chloro-benzhydrylation 2.4.4 Chloro-γ-hydroxylation 2.5 Vilsmeier–Haack Reactions 2.6 Cross-Coupling Reaction of gem -Dibromoalkenes in the Presence of N -Nucleophiles 3 Transformations of α-Haloenamides 3.1 Suzuki and Sonogashira Reactions 3.2 Heck Reaction 3.3 Stille Reaction 3.4 Miscellaneous Applications 3.4 Carbonylation 3.4.2 Reduction 3.4.3 Synthesis of α-Fluoroimides 3.4.4 Palladium-Catalyzed Intramolecular Cyclization 4 Conclusion [ABSTRACT FROM AUTHOR]

We report a tri-n-butyl phosphine catalyzed regio- and stereo-selective hydroboration of ynamides to yield (Z)-β-borylenamides in good yields. Surprisingly, a formal cis addition to the triple bond was observed as confirmed by NMR and X-ray crystallography. 31P NMR studies suggest that a zwitterionic vinylphosphonium intermediate is key in the mechanism. The resulting products were further transformed to β-CF3 enamides via stereoretentive trifluoromethylation. [ABSTRACT FROM AUTHOR]

The silica gel promoted or solvent-promoted protonative intramolecular cyclization of ynamides containing an o -(methylthio)aryl group resulted in the one-pot formation of biologically important -benzo[ b ]thiophenes. Compared with ynamide activation methods that use strong Brønsted acids or expensive transition metals, this protocol is mild and economical. Due to these merits, various functionalized 2-amidobenzo[ b ]thiophenes were furnished in a convenient way. [ABSTRACT FROM AUTHOR]

A chemo‐selective copper(I)‐catalyzed oxytrifluoromethylation of N‐Boc‐ynamides with TMSCF3 has been achieved, affording the trifluoromethylated oxazolones in 51–99% yields. The reaction proceeds at room temperature and tolerates a variety of functional groups such as −X, −OMe, alkenyl, and other substituents. The resulting oxazolones provide access to α‐CF3‐substituted amines through decarboxylative reduction. [ABSTRACT FROM AUTHOR]

Ynamides, a class of novel coupling reagents for peptide synthesis, facilitated peptide bond formation in a one‐pot, two‐step manner with α‐acyloxyenamide active esters of amino acids as stable intermediates. Ynamide‐mediated peptide synthesis proceeded by a reaction mechanism that is completely different from that of conventional coupling reagents and exhibited superiority in addressing the issue of racemization/epimerization during peptide bond formation. Herein, we present a systematic mechanistic analysis, including kinetics and Brønsted‐type structure–reactivity studies and density functional theory calculations, providing unprecedented mechanistic insight into ynamide‐mediated peptide bond formation. Based on these mechanistic studies, significant improvements were made, and the applicability of ynamide‐mediated peptide bond formation was successfully expanded to peptide fragment condensation, head‐to‐tail cyclization and solid‐phase peptide synthesis. [ABSTRACT FROM AUTHOR]

Ynamides, a class of novel coupling reagents for peptide synthesis, facilitated peptide bond formation in a one‐pot, two‐step manner with α‐acyloxyenamide active esters of amino acids as stable intermediates. Ynamide‐mediated peptide synthesis proceeded by a reaction mechanism that is completely different from that of conventional coupling reagents and exhibited superiority in addressing the issue of racemization/epimerization during peptide bond formation. Herein, we present a systematic mechanistic analysis, including kinetics and Brønsted‐type structure–reactivity studies and density functional theory calculations, providing unprecedented mechanistic insight into ynamide‐mediated peptide bond formation. Based on these mechanistic studies, significant improvements were made, and the applicability of ynamide‐mediated peptide bond formation was successfully expanded to peptide fragment condensation, head‐to‐tail cyclization and solid‐phase peptide synthesis. [ABSTRACT FROM AUTHOR]

An auto-tandem catalytic, branched-selective rearrangement of substituted N-alloc-N-allyl ynamides was developed. This reaction provides ready access to complex quaternary nitrile products with vinylogous stereocentres in excellent diastereoselectivity, including contiguous all-carbon quaternary centres. The stereochemical outcome is determined via a Pd(0) catalysed dipolar ketenimine aza-Claisen rearrangement and computational studies exemplify the key role ligand geometry plays. [ABSTRACT FROM AUTHOR]

The mechanism of silver-catalyzed hydroamidation of siloxy-alkynes reaction remains controversial. Using density functional theory (DFT), we revealed that the reaction takes place through a silylium ion migration mediated hydroamination (SMH) pathway. The SMH pathway goes through two steps, the first step is Ag+ promoted proton and silylium ion exchange between siloxy-alkynes and amide, leading to ketene and silyl-imines, the second step is Ag+ catalyzed nucleophilic addition between ketene and silyl-imines, following with a silylium ion migration afford the final product. In this reaction, Ag+ activates the siloxy-alkyne into silylium ion (TIPS+) and silver-ketene through the p–π conjugate effect, the silylium ion then catalyzes the reaction. According to our calculation, the scopes of alkynes in this reaction may be extended to silyl-substituted ynamines or silyl-substituted ynamides. The scopes of amide may be extended into the p–π conjugate system such as diazoles, diazepines, etc. Our calculations also reveal a concise way to construct enamides through Ag+ catalyzed nucleophilic addition between substituted-ketenes and silyl-substituted p–π conjugate system. Silver-catalyzed hydroamidation of siloxy-alkynes is a successful approach for the hydroamidation of internal alkynes, however the mechanism of this reaction is poorly understood. Here, the authors use density functional theory calculations to reveal that the reaction takes place through a silver activated silylium ion migration mediated hydroamidation pathway. [ABSTRACT FROM AUTHOR]

Transition metal catalysis is a useful tool for C−C bond‐forming reactions. Of special interest is the hydroalkynylation reaction of alkynes, which provides a simple method for the synthesis of enynes representing interesting structural motifs in organic chemistry. So far, there are only a few examples of gold(I)‐catalyzed hydroalkynylation reactions. Herein, we were able to show experimentally that the gold(I)‐catalyzed hydroalkynylation of ynamides leads regio‐ and stereoselectively to the corresponding ynenamides, a rather unknown type of molecule. A wide range of products could be generated with yields up to 90 % and, in contrast to many other gold‐catalyzed alkyne dimerization reactions, alkyl groups are tolerated. Quantum chemical calculations and NMR labelling experiments reveal a mechanism via dual gold catalysis. [ABSTRACT FROM AUTHOR]

A copper-catalysed three-component coupling reaction between a carbonyl derivative, a terminal ynamide and an amine has been developed for the one-pot green construction of γ-amino-ynamides from simple starting materials and with a broad functional group tolerance.The copper-zeolite-catalysed three-component coupling reaction between an aldehyde or a ketone, a terminal ynamide and an amine is reported. The so-elaborated methods, dubbed AYA (i.e. Aldehyde-Ynamide-Amine) and KYA (i.e. Ketone-Ynamide-Amine), enable the straightforward one-pot synthesis of γ-amino-ynamides from simple starting materials and with a broad functional group tolerance. Moreover, AYA/KYA processes are performed at room temperature under solvent-free conditions or in ethyl acetate as green solvent in the presence of a copper-based easy-to-recover/-remove catalyst, at low loading (3 mol%), making these synthetic methods fully green. [ABSTRACT FROM AUTHOR]

The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon has been explored for the first time in a novel iron(III)-catalyzed tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to an expeditious assembly of synthetically important functionalized cyclopenta[b]indoles. [ABSTRACT FROM AUTHOR]

A straightforward and sustainable approach for the 1,2-addition of propiolic acids to ynamide has led to bench-stable sp2 (E)-enol-enamides of enediynes and dienynes. The reaction is chemo-, regio-, and stereoselective and does not require metal catalysts and solvent. The ynamide motif is extremely amenable to functionalization in the presence of the tethered alkyne triple bond. The synthetic technique is operationally simple; no hydrolysis of ketenimine species occurs under acidic conditions. The transformation tolerates a wide range of common functional groups, constructing a library of highly functionalized 1,5,5′/6′-enediynes and 1,5,5′-dienynes of sp2 (E)-N,O-acetal skeletons. [ABSTRACT FROM AUTHOR]

α-Imino gold carbenoid species have been recognized as key intermediates in a plethora of processes involving gold-activated alkynes. Here, we explored the pathways of the Au(I)-catalyzed [3 + 2] reaction between the mild nucleophiles: anthranil, 1,2,4-oxadiazole, or 4,5-dihydro-1,2,4-oxadiazole, and an ynamide, PhC≡C-N(Ts)Me, proceeding via the formation of the aforementioned α-imino gold carbene intermediate which, after intramolecular capture, regioselectively produces 2-amino-3-phenyl-7-acyl indoles, N-acyl-5-aminoimidazoles, or N-alkyl-4-aminoimidazoles, respectively. In all cases, the regioselectivity of the substituents at 2, 3 in the 7-acyl-indole ring and 4, 5 in the substituted imidazole ring is decided at the first transition state, involving the attack of nitrogen on the C1 or C2 carbon of the activated ynamide. A subsequent and steep energy drop furnishes the key α-imino gold carbene. These features are more pronounced for anthranil and 4,5-dihydro-1,2,4-oxadiazole reactions. Strikingly, in the 4,5-dihydro-1,2,4-oxadiazole reaction the significant drop of energy is due to the formation of an unstable α-imino gold carbene, which after a spontaneous benzaldehyde elimination is converted to a stabilized one. Compared to anthranil, the reaction pathways for 1,2,4-oxadiazoles or 4,5-dihydro-1,2,4-oxadiazoles are found to be significantly more complex than anticipated in the original research. For instance, compared to the formation of a five-member ring from the α-imino gold carbene, one competitive route involves the formation of intermediates consisting of a four-member ring condensed with a three-member ring, which after a metathesis and ring expansion led to the imidazole ring. [ABSTRACT FROM AUTHOR]

[Display omitted] An In(OTf) 3 -catalyzed oxygenative bifunctionalization reaction has been developed for the facile synthesis of various α-functionalized ketones. A wide range of aryl sulfoxides and electron-rich arylalkynes prove to be suitable substrates for this transformation. The potential of our method was then extended to the synthesis of 8-substituted quinolines from ynamides and quinoline- N -oxides. [ABSTRACT FROM AUTHOR]