Nonactivated Alkynes Research Articles

Electrochemical Organoselenium Catalysis for the Selective Activation of Alkynes: Easy Access to Carbonyl-pyrroles/oxazoles from N-Propargyl Enamines/Amides.

Intramolecular electro-oxidative addition of enamines or amides to nonactivated alkynes was attained to access carbonyl-pyrroles or -oxazoles from N-propargyl derivatives. Organoselenium was employed as the electrocatalyst, which played a crucial role as a π-Lewis acid and selectively activated the alkyne for the successful nucleophilic addition. The synthetic strategy permits a wide range of substrate scope up to 93% yield. Several mechanistic experiments, including the isolation of a selenium-incorporated intermediate adduct, enlighten the electrocatalytic pathway.

Construction of Heterobimetallic Catalytic Scaffold with a Carbene-Bipyridine Ligand: Gold–Zinc Two-Metal Catalysis for Intermolecular Addition of O-Nucleophiles to Nonactivated Alkynes

Construction of Heterobimetallic Catalytic Scaffold with a Carbene-Bipyridine Ligand: Gold–Zinc Two-Metal Catalysis for Intermolecular Addition of <i>O</i>-Nucleophiles to Nonactivated Alkynes

Visible-Light-Induced Organocatalyzed [2+1] Cyclization of Alkynes and (Trifluoroacetyl)silanes

AbstractThe synthesis of common cyclopropenes has been widely studied, but the synthesis of cyclopropenols is a significant challenge. Here, we highlight our recent work on the synthesis of trifluoromethylated cyclopropenols through a [2+1] cycloaddition reaction between alkynes and (trifluoroacetyl)silanes under visible-light-induced organocatalysis. The novel amphiphilic donor–acceptor carbenes derived from (trifluoroacetyl)silanes can react effectively with both activated and nonactivated alkynes. A broad substrate scope and a good functional-group tolerance have been achieved. Moreover, the synthetic potential of this reaction was highlighted by a gram-scale reaction and the one-pot diastereoselective synthesis of trifluoromethylated cyclopropanols.

Metal-free one-pot oxidative conversion: Molecular Iodine Mediated Oxidation Organic Reactions

Various oxidative compounds such as aldehyde, ketone ester, and acids can be produced in large yields by an effective iodine-mediated oxidative reaction of organic molecules. Molecular iodine is a generally available and commercially extremely inexpensive substance that induces oxidative esterification. With the comparison with different Brønsted acid catalysis, molecular iodine or iodophilic activations proceed the reaction onto a deoxygenation pathway. With only a few mol% of I2, the oxidation occurs very quickly at room temperature. This approach could also be used to transport different benzil derivatives from nonactivated alkynes, such as diaryl acetylenes. Molecular iodine with several mild reagents such as aq. NH3, ∼30% aq. H2O2 and DMSO might be used to convert various one degree alcohols, particularly benzylic alcohols, into the corresponding aromatic amides in suffiently high yields in a one-pot method. Similarly, by treating different benzylic chloride, bromide and iodide with a molecular iodine oxidation medium, the corresponding aromatic amides may be prepared in a one-pot method. The reactions in this section include transformation of several compounds into their respective oxidative products with the metal-free one-pot oxidative.

Synthesis of Cyclopropenols Enabled by Visible-Light-Induced Organocatalyzed [2+1] Cyclization.

Although the synthesis of common cyclopropenes has been well studied, the access to cyclopropenols is rather limited. Herein, we report the first synthesis of α-trifluoromethylated cyclopropenols via 2+1 cycloaddition reactions between alkynes and trifluoroacylsilanes, enabled by visible-light-induced organocatalysis. The novel ambiphilic donor-acceptor carbenes derived from trifluoroacetylsilanes reacted efficiently with both activated and non-activated alkynes. The reaction features simple operation, mild conditions, broad substrate scope and good functional group tolerance. The synthetic potential of the reaction is highlighted by the gram-scale reactions and first synthesis of α-trifluoromethylated cyclopropanols through the combination of the 2+1 cyclization and high diastereoselective hydrogenation reaction in one pot.

Metal-Free Iodine-Catalyzed Oxidation of Ynamides and Diaryl Acetylenes into 1,2-Diketo Compounds.

Metal-free oxidation of ynamides is described, employing pyridine- N-oxides as oxidants under molecular iodine catalysis. In stark contrast to Brønsted acid catalysis, iodophilic activation of ynamides diverts the reaction manifold into a dioxygenation pathway. This oxidation is very rapid at room temperature with only 2.5 mol % I2. Furthermore, this protocol could be extended to nonactivated alkynes, such as diarylacetylenes, to deliver various benzil derivatives.

Markovnikov-Selective Palladium Catalyst for Carbonylation of Alkynes with Heteroarenes.

A new class of palladium catalysts, based on heterocyclic diphosphines, was rationally designed and synthesized. Application of one of these catalysts allows novel Markovnikov-selective carbonylation of non-activated alkynes with heteroarenes to give the corresponding branched α,β-unsaturated ketones in excellent yields (up to 97 %) and regioselectivities (b/l up to 99:1). In addition to heteroarenes, other common nucloephiles (alcohol, phenol, amine, and amide) furnish the desired carbonylation products smoothly in high yields.

ChemInform Abstract: A Solvent‐Free and One‐Pot Strategy for Ecocompatible Synthesis of Substituted Benzofurans from Various Salicylaldehydes, Secondary Amines, and Nonactivated Alkynes Catalyzed by Copper(I) Oxide Nanoparticles.

AbstractAromatic amines such as aniline and 4‐chloroaniline are unreactive under the developed conditions.

Trifluoroethanol as an efficient reaction media for the synthesis of pyran skeleton through domino Knoevenagel–hetero-Diels–Alder reaction with non-activated alkynes

Trifluoroethanol as an efficient media for the domino Knoevenagel–hetero-Diels–Alder reaction of O-propargyloxy benzaldehydes as non-activated terminal alkynes with some active methylene compounds has been described. Short reaction time, easy work-up, good to high yields, and mild reaction conditions are advantages of this new media.

A Solvent-Free and One-Pot Strategy for Ecocompatible Synthesis of Substituted­ Benzofurans from Various Salicylaldehydes, Secondary Amines, and Nonactivated Alkynes Catalyzed by Copper(I) Oxide Nanoparticles

Copper(I) oxide nanoparticles (CONPs) catalyze multicomponent coupling/cycloisomerization reactions between various 2-hydroxybenzaldehydes, secondary amines, and nonactivated alkynes to give 2,3-disubstituted 1-benzofurans. All reactions are carried out under solvent- and ligand-free conditions at 100 °C in air. The combination of copper-catalyzed C–H activation and an O-annulation process is essential for this transformation. This methodology provides rapid access to substituted 1-benzofurans in good to excellent yields with high atom economy and high catalytic efficiency. This procedure eliminates the need for propargylamine derivatives, uncyclized intermediates that make purification difficult. The CONPs and tetrabutylammonium bromide were reused successfully for up to five times.

Direct Gold-Catalyzed Regioselective Tetrafunctionalization of Nonactivated Alkynes

A simple and efficient method based on gold catalysis is reported for the synthesis of halogen-functionalized pyrrolidine ­aminals. A new alkyne tetrafunctionalization strategy is proposed for the first time.

Synergistic Iron-and-Amine Catalysis in Carbocyclizations

The fruitful merger of iron catalysis to amine catalysis was successfully applied in the direct intramolecular addition of aldehydes to non-activated alkynes. Accordingly, the carbocyclizations of a range of formyl-alkynes afforded the corresponding cyclopentanes in good to excellent yields. Experimental evidence tends to support a synergistic enamine/π-activation reaction mechanism.

Chelator-Accelerated One-Pot ‘Click’ Labeling of Small Molecule Tracers with 2-[18F]Fluoroethyl Azide

2-[18F]Fluoroethyl azide ([18F]FEA) can readily be obtained by nucleophilic substitution of 2-azidoethyl-4-toluenesulfonate with [18F]fluoride (half-life 110 min), and has become widely used as a reagent for ‘click’ labeling of PET tracers. However, distillation of [18F]FEA is typically required, which is time-consuming and unpractical for routine applications. In addition, copper(I)-catalyzed cycloaddition of [18F]FEA with non-activated alkynes, and with substrates containing labile functional groups, can be challenging. Herein, we report a highly efficient and practical ligand-accelerated one-pot/two-step method for ‘click’ labeling of small molecule tracers with [18F]FEA. The method exploits the ability of the copper(I) ligand bathophenanthrolinedisulfonate to accelerate the rate of the cycloaddition reaction. As a result, alkynes can be added directly to the crude reaction mixture containing [18F]FEA, and as cyclisation occurs almost immediately at room temperature, the reaction is tolerant to labile functional groups. The method was demonstrated by reacting [18F]FEA with a series of alkyne-functionalized 6-halopurines to give the corresponding triazoles in 55–76% analytical radiochemical yield.

ChemInform Abstract: Palladium‐Catalyzed Cyanation of Nonactivated Alkynes; Development of Cyanopalladation and Its Application to Cyclization and Cycloaddition Reactions

AbstractReview: ca. 50 refs.

Palladium-Catalyzed Cyanation of Nonactivated Alkynes; Development of Cyanopalladation and Its Application to Cyclization and Cycloaddition Reactions

This account describes the cyanopalladation of simple and nonactivated alkynes and their application to various cyclization and cycloaddition protocols. A unique feature of cyanopalladation is the direct nucleophilic cyanation with an external CN source such as TMSCN of simple alkynes, which can be effectively activated by Pd(II) under molecular oxygen. There are two possible pathways: syn- and anti-cyanopalladation, which are strongly influenced by the structure of the substrates. The former is usually the major pathway because nucleophilic cyanation is favored to occur at the less hindered alkynyl carbon. The latter could be controlled by the Markovnikov rule, with cyanide directly attacking the π-complex of alkynyl carbons from the site opposite Pd(II). Once the cyanoalkenyl Pd(II) species are formed by cyanopalladation, these intermediates act as useful precursors for sequential carbon–carbon bond-forming reactions, such as 5-exo and 6-endo cyclizations and [4+2] cycloaddition. Cyclization is triggered by regio- and stereoselective cyanopalladation, and [4+2] cycloaddition gives up to five stereogenic centers through the formation of four C–C bonds in a single operation. The reaction pathways and the origin of stereochemistry are also described. 1 Introduction 2 Catalytic 1,2-Dicyanation 2.1 Terminal Alkynes 2.2 Internal Alkynes 2.3 Synthetic Applications 3 Dicyanative Cyclization 3.1 5-exo Cyclization 3.2 Diyne Cyclization 3.2.1 Terminal Diynes 3.2.2 Internal Diynes 3.3 6-endo Cyclization 4 Dicyanative [4+2] Cycloaddition 5 Conclusion

Regio- and Stereoselective Copper-Catalyzed Addition of Aromatic and Aliphatic Thiols to Terminal and Internal Nonactivated Alkynes

Regio- and Stereoselective Copper-Catalyzed Addition of Aromatic and Aliphatic Thiols to Terminal and Internal Nonactivated Alkynes

Solvent-free hydration of alkynes over a heterogeneous silver exchanged silicotungstic acid catalyst

Silver exchanged silicotungstic acid (AgSTA) catalysts were prepared and characterized by X-ray diffraction, FT-IR spectroscopy, laser Raman, temperature programmed desorption of ammonia, FT-IR pyridine adsorption and X-ray photo electron spectroscopy. The activity of the catalysts was evaluated for the hydration of non-activated alkynes to corresponding carbonyl compounds without addition of any acid co-catalyst under solvent-free conditions. The highest catalytic activity was obtained for the catalyst with partially silver exchanged STA. This catalytic system provides one of the most straight forward syntheses of carbonyl compounds from terminal alkynes with Markovnikov-type regioselectivity. The catalyst can be recovered by simple filtration and is reusable without loss of activity and selectivity. A plausible reaction mechanism for the AgSTA catalyzed hydration of alkynes is proposed.

ChemInform Abstract: Thiol Addition to Aryl Propargyl Alcohols under Mild Conditions: An Accelerating Neighboring Group Effect.

Abstract Aryl alkynols provide a convenient entry into α-hydroxyketones via thiol addition followed by hydrolysis. Thiols have been added to several non-activated alkynes under mild, basic conditions. A coordinating functional group in close proximity to the triple bond facilitates this reaction.

β‐Diketiminate Zinc Complexes for the Hydroamination of Alkynes

AbstractA series of electronically and sterically modified β‐diketiminate methylzinc complexes [{N,N′‐bis(2,6‐diisopropylphenyl)‐β‐diketiminato}methylzinc] (1), [{N,N′‐bis(2‐isopropylphenyl)‐β‐diketiminato}methylzinc] (2), [{N,N′‐bis(2,4,6‐trimethylphenyl)‐β‐diketiminato}methylzinc] (3), [{N,N′‐bis(4‐methoxyphenyl)‐β‐diketiminato}methylzinc] (4), a bis(β‐diketiminato)zinc compound [bis{N,N′‐bis(4‐methoxyphenyl)‐β‐diketiminato}zinc] (5), and a β‐diketiminate bis(trimethylsilylamido)zinc complex [{2‐(1‐cyclohexylimidazolidine‐2‐ylidene)‐1‐methylethylidene‐(2,6‐diisopropylphenyl)aminato}bis(trimethysilylamido)zinc] (6) were prepared and structurally characterized by single‐crystal X‐ray diffraction. All methylzinc compounds exhibit a trigonal‐planar coordinated zinc atom, with the exception of polymeric compound 4, in which intermolecular coordination of the OMe group to the zinc atom additionally takes place. All zinc complexes were investigated as catalysts in the intramolecular hydroamination of nonactivated alkynes and show high catalytic activity in the presence of the cocatalyst [PhNMe2H][SO3CF3]. The zinc complex 1 shows the highest catalytic activityin most of the cyclization reactions. In this context, it waspossible to isolate the intermediate, which was formed bythe reaction of the precatalyst 1 and the cocatalyst [PhNMe2H][SO3CF3]. The resulting zinc catalyst [{N,N′‐bis(2,6‐diisopropylphenyl)‐β‐diketiminato}(trifluoromethanesulfonate)zinc]·thf (7) was structurally characterized by single‐crystal X‐ray diffraction. The zinc complex 7 show the same catalytic activity in the hydroamination when an equimolar mixture of the precatalyst 1 and the cocatalyst was used. It is supposed that the high steric bulk of the precatalyst 1 protects the Lewis acid zinc center from polar functional groups but allows interactions for the cyclization process.

Cyclocarboamination of Alkynes with Aziridines: Synthesis of 2,3-Dihydropyrroles by a Catalyzed Formal [3 + 2] Cycloaddition

An efficient cyclocarboamination reaction of nonactivated alkynes with aziridines, catalyzed by Lewis or Bronsted acids, to form 2,3-dihydropyrroles through a formal [3+2] cycloaddition, is described. The reaction provides a wide range of polysubstituted dihydropyrroles in a highly regioselective manner, is scalable, proceeds under mild reaction conditions, and uses low catalyst loadings.