Difunctionalization Of Alkynes Research Articles

A multicomponent synthesis of stereodefined olefins via nickel catalysis and single electron/triplet energy transfer

Unsaturated carbon–carbon bonds are one of the most common and important structural motifs in many organic molecules, stimulating the continuous development of general, efficient and practical strategies for their functionalization. Here, we report a one-pot difunctionalization of alkynes via a photoredox/nickel dual-catalysed three-component cross-coupling reaction under mild conditions, providing access to a series of highly important tri-substituted alkenes. Notably, in contrast to traditional methods that are based on the steric hindrance of the substrates to control the reaction selectivity, both E- and Z-isomers of tri-substituted alkenes, which are often energetically close, can be obtained by choosing an appropriate photocatalyst with a suitable triplet state energy. Beyond the immediate practicality of this transformation, this newly developed methodology might inspire the development of diverse and important one-pot functionalizations of carbon–carbon multiple bonds via photoredox and transition-metal dual-catalysed multicomponent reactions. The synthesis of stereodefined alkenes is challenging, and often relies on the steric bias of the substituents. Here the authors report a photoredox/nickel catalysed difunctionalization of alkynes, giving access to either E- or Z-tri-substituted alkenes, depending on the photocatalyst used.

Lactone Synthesis by Enantioselective Orthogonal Tandem Catalysis

AbstractIn this work, we report enantioselective orthogonal tandem catalysis for the one pot conversion of Meldrum's acid derivatives and alkynes into δ‐lactones. This new transformation, which resembles a formal [4+2] cycloaddition with concomitant decarboxylation and loss of acetone, proceeds in high yields and excellent enantioselectivity (up to 99 % ee) over a broad substrate scope. The products are densely functionalized and ripe for further transformations, as demonstrated here by both ring‐opening reactions and reduction to saturated lactones. It was discovered that a new and serendipitously formed AgI‐Me‐StackPhos complex efficiently catalyzes the highly selective 6‐endo‐dig cyclization, completely reversing the regiochemistry that has been previously reported in related systems. More generally, in this study we identify a pair of compatible catalysts for alkyne difunctionalization that operate concurrently, which enable the alkyne to act as both a nucleophile and an electrophile in sequential one‐pot transformations.

Regioselective Intermolecular Sulfur-Oxygen Difunctionalization (Phenoxysulfonylation) of Alkynes: One-Pot Construction of ( Z)-β-Phenoxy Vinylsulfones.

The first regioselective phenoxysulfonylation of alkynes with sodium sulfinate and phenol catalyzed by I2/base has been uncovered. This metal-free, one-pot alkyne difunctionalization process provides various ( Z)-β-phenoxy vinylsulfones under mild reaction conditions. A variety of terminal as well as internal alkynes and sodium sulfinates and a wide range of phenols/thiophenols and naphthols are viable in this transformation. Green protocol and wide substrate scope are the remarkable characteristics of this multicomponent procedure.

Copper-Catalyzed Intramolecular Chalcogenoamination of Enynyl Azides: Synthesis of 5-Selenyl/Sulfenyl Nicotinates.

A novel methodology for the synthesis of 5-selenyl/sulfenyl nicotinates involving copper-catalyzed organochalcogenyl aza-annulation of enynyl azide with diorganyl-dichalcogenides has been described. This method offers difunctionalization of alkynes via regioselective intramolecular chalcogenoamination in one pot to provide substituted 5-chalcogenyl nicotinates in good to excellent yields. The resulting nicotinates provide access to their oxides, sulfones, and acid derivatives.

Metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM).

A metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM) was described herein. The reaction was conducted under mild conditions without any catalysts or additives. Preliminary mechanism studies revealed that the formation of VQM was the key for this alkyne di-functionalization reaction. The reaction could be applied in the enantioselective asymmetric synthesis of axially chiral styrene. Furthermore, the selenosulfonylation adducts can be transformed into useful naphtho[2,1-b]furan and benzofuran scaffolds.

Access to 3‐(2‐Oxoalkyl)‐azaspiro[4.5]trienones via Acid‐Triggered Oxidative Cascade Reaction through Alkenyl Peroxide Radical Intermediate

AbstractAzaspiro[4.5]trienones bearing ketone side chains at the 3‐position are prepared from N‐alkyl‐arylpropiolamides and ketones via oxidative 1,2‐difunctionalization of alkynes. The cascade sequence starts with the generation of alkenyl peroxide intermediates, which are obtained by addition of tert‐butyl hydroperoxide to ketones in presence of a catalytic amount of a strong acid. Then, the ketone radical adds to alkynes, followed by spirocyclization and dearomatization process. This method represents a new example of difunctionalization of alkynes with simultaneous formation of two carbon−carbon single bonds and one carbon−oxygen double bond in one step.magnified image

Retraction of "Iron-Catalyzed Three-Component Reaction: Synthesis of Fluoroalkylated 2 H-Azirines".

A convenient route for the synthesis of fluoroalkylated 2H-azirines has been developed, involving an iron-catalyzed azidoperfluoroalkylation of alkynes with perfluoroalkyl iodides and trimethylsilyl azide. This novel alkyne difunctionalization reaction produces versatile fluoroalkylated 2H-azirines, paving the way for further modifications into various heterocycles.

Synthesis of Difluoroalkyl Unsaturated β-Amino Acid Derivatives Exclusively through Alkyne Difunctionalization.

Alkynes difunctionalization is a powerful strategy in organic synthesis that provides a convenient synthetic entry for internal alkenes. The main challenge in this field was considered to be the geometry control of the newly formed double bond (thermodynamically controlled or kinetically controlled). Herein, we report a novel procedure (through the cyclic compounds broken) to completely control the regioselectivity of olefins. The products, difluoroalkyl unsaturated β-amino acid derivatives, have potential applications in some important pharmaceuticals on account of the special nature of fluorine atoms.

Syn-Selective alkylarylation of terminal alkynes via the combination of photoredox and nickel catalysis

Substituted alkenes are pivotal structural motifs found in pharmaceuticals and agrochemicals. Although numerous methods have been developed to construct substituted alkenes, a generally efficient, mild, catalytic platform for the conversion of alkynes to this highly functionalized scaffold via successive C–C bond forming steps remains in high demand. Here we describe an intermolecular, regio- and syn-stereoselective alkylarylation of terminal alkynes with tertiary alkyl oxalates via photoredox-Ni dual catalysis. This catalytic protocol, synergistically combining Ir/Ni-catalyzed alkyne difunctionalization with photoinduced alkene isomerization, affords trisubstituted alkenes with excellent efficiency and syn-stereoselectivity. The mild conditions tolerate many functional groups, allowing for a broad scope with respect to terminal alkynes, aryl bromides, and alkyl oxalates.

Regio‐ and Stereoselective Vicinal syn‐Arylation‐Trifluoromethylation of Terminal Arylacetylenes

AbstractOne‐pot three‐component syn‐arylation‐trifluoromethylation of terminal arylalkynes is developed by using an isolated (phen)Cu(III)(CF3)3 complex (phen: phenanthroline) and aryl boronic acids. This reaction is chemoselective that can suppress the competing trifluoromethylation of alkyne C−H and aryl boronic acids. It is also regioselective to install an aryl group on Cα and a CF3 group on Cβ of arylalkynes. Finally, unusual syn‐difunctionalization chemistry is achieved that is complementary to the general anti‐stereochemistry for difunctionalization of alkynes involving trifluoromethylation. The use of a Cu(III)−CF3 complex is crucial to the success that not only acts as a reactive CF3 precursor, but is also responsible for the unusual syn‐stereochemistry. This study allows ready access to vicinal arylated‐trifluoromethylated olefins, which is a widely existing structural motif in many biologically active compounds.

α‐Amino Acid Sulfonamides as Versatile Sulfonylation Reagents: Silver‐Catalyzed Synthesis of Coumarins and Oxindoles by Radical Cyclization

We developed a silver‐catalyzed strategy for the generation of sulfonyl radicals from sulfonamides derived from α‐amino acids. The reaction proceeded via a decarboxylation, N–S bond cleavage and radical cyclization sequence and allows the difunctionalization of alkynes and the synthesis of 3‐sulfonylated coumarins. The reaction tolerated a broad scope of substrates and functional groups and could be extended to the synthesis of oxindoles and an isoquinolinedione by the capturing of the sulfonyl radical with an alkene moiety. Moreover, the proposed mechanism was supported experimentally and by DFT calculations.

Highly Efficient Recyclable Sol Gel Polymer Catalyzed One Pot Difunctionalization of Alkynes.

Amino-bridged gel polymer P1 was discovered to catalyze alkyne halo-functionalization in excellent yields, regioselectivity, functional group compatibility, and recyclability. We have observed that both aromatic and aliphatic alkynes can be converted to α,α-dihalogenated ketones in the presence of polymer P1 under metal-free conditions at room temperature within a short reaction time.

Palladium-Catalyzed Regio- and Stereoselective Coupling-Addition of Propiolates with Arylsulfonyl Hydrazides: A Pattern for Difunctionalization of Alkynes.

A new pattern for difunctionalization of alkynes via a palladium-catalyzed regio- and stereoselective coupling-addition of propiolates with arylsulfonyl hydrazides is disclosed. The approach enables the synthesis of various highly functionalized ( E)-vinylsulfones in satisfactory yields. Arylsulfonyl hydrazides act as both aryl and sulfonyl sources via selective cleavage of Ar(C)-S and S-N bonds, which are simultaneously incorporated onto the terminal carbon atom of an alkyne molecule.

Visible-Light-Driven Alkyne Hydro-/Carbocarboxylation Using CO2 via Iridium/Cobalt Dual Catalysis for Divergent Heterocycle Synthesis.

We present herein the first visible-light-driven hydrocarboxylation as well as carbocarboxylation of alkynes using CO2 via an iridium/cobalt dual catalysis. Such transformations provide access to various pharmaceutically important heterocycles in a one-pot procedure from readily available alkynes. Coumarins, 2-quinolones, and 2-benzoxepinones were directly accessed through a one-pot alkyne hydrocarboxylation/alkene isomerization/cyclization sequence in which the Ir photocatalyst serves a dual role to promote single-electron transfer in alkyne hydrocarboxylation and energy transfer in the subsequent alkene isomerization. Moreover, an unprecedented cobalt carboxylation/acyl migration cascade enables alkyne difunctionalization to introduce γ-hydroxybutenolides with high efficiency. We expect that this cascade strategy will inspire new perspectives for alkyne and alkene difunctionalization.

Visible-Light-Mediated Ipso-Carboacylation of Alkynes: Synthesis of 3-Acylspiro[4,5]trienones from N-(p-Methoxyaryl)propiolamides and Acyl Chlorides.

A novel visible-light-mediated ipso-carboacylation of N-(p-methoxyaryl)propiolamides with acyl chloride has been established for the synthesis of diverse 3-acylspiro[4,5]trienones with high selectivity and efficiency. This method represents a new difunctionalization of alkynes through cross coupling of the acyl chloride C-Cl bonds with an ipso-aromatic carbon by simultaneously forming two new carbon-carbon bonds and one carbon-oxygen double bond.

Difunctionalization of Alkynes: Synthesis of Novel Fluoropolymer Materials

A Pd‐catalyzed multi‐component carbonylative difluoroalkylation/perfluoroalkylation through the alkyne difunctionalization process has been developed. Besides, new functional fluoropolymer materials have been successfully synthesized. Owing to the presence of the fluorine element, the materials present excellent chemical resistance, high‐temperature‐resistance and outstanding hydrophobicity simultaneously, which may significantly make them great appealing in the industrial production and life science as well.

Metal-free difunctionalization of alkynes leading to alkenyl dithiocyanates and alkenyl diselenocyanates at room temperature.

A simple and practical method for the synthesis of alkenyl dithiocyanates and alkenyl diselenocyanates has been developed via stereoselective difunctionalization of alkynes with NaSCN or KSeCN at room temperature. Through this methodology, a series of alkenyl dithiocyanates and alkenyl diselenocyanates could be efficiently and conveniently obtained in moderate to good yields under mild and metal-free conditions by the simple use of oxone and PhI(OAc)2 as the oxidants.

KI as iodine source for the synthesis of E-iodovinyl sulfones via metal-free iodosulfonylation of terminal alkynes

GRAPHICAL ABSTRACT

Copper‐Catalyzed Acyloxycyanation of Alkynes with Acetonitrile: Regioselective Construction of Cyclic Acrylonitriles by 6‐endo or 5‐exo Cyclization

AbstractAn efficient difunctionalization of alkynes by tandem iodolactonization and copper‐catalyzed cyanation using acetonitrile as a cyanating reagent is reported for the first time. This approach can afford cyano‐containing isocoumarin or phthalide derivatives in good yields by careful choice of the carboxylate nucleophiles and electrophilic iodine sources. Thus, an acyloxycyanation strategy can be achieved in good yields and high regioselectivity of either 6‐endo or 5‐exo cyclization products.magnified image

Stereoselective Vicinal Difunctionalization of Alkynes through a Three‐Component Reaction of Alkynes, Sodium Sulfinates, and Togni Reagent

AbstractStereoselective vicinal difunctionalization of alkynes through trifluoromethylation and sulfonylation via a three‐component reaction of alkynes, sodium sulfinates, and Togni reagent under catalyst‐ and additive‐free conditions has been realized. This reaction proceeds at room temperature in dimethyl sulfoxide (DMSO), providing (E)‐β‐trifluoromethylvinyl sulfones in moderate to good yields. The advantages of this tandem radical process include extremely mild conditions, excellent stereoselectivity, and easy experimental operation.magnified image