634602-53-2

Upstream product

• 3034-86-4 4-ethynylbenzoic acid methyl ester 
• 105-56-6 ethyl 2-cyanoacetate 
• 619-44-3 methyl 4-iodobenzoate 
• 61266-36-2 methyl 4-(3-hydroxypropynyl)benzoate 
• 69316-08-1 methyl-4-(2-cyanoacetyl)benzoate 
• 73789-56-7 N-isocyaniminotriphenylphosphorane 
• 506-78-5 cyanogen iodide 
• 75867-41-3 4-trimethylsilanylethynyl-benzoic acid methyl ester 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 15328-32-2 1-cyanobenzotriazole 

Relevant academic research and scientific papers

Copper-catalyzed C-H cyanation of terminal alkynes with cyanogen iodide

A copper-catalyzed reaction of terminal alkynes with cyanogen iodide (ICN) that produces alkynyl cyanides has been developed. The use of tetramethylpiperidine as a sterically congested base was successful in this reaction. Some control experiments revealed that the reaction involves the noncatalyzed formation of alkynyl iodides followed by copper-catalyzed cyanation of the iodides without the formation of copper(I) acetylide. This observation contrasts with what is normally observed in various copper-mediated reactions using terminal alkynes.

An aerobic and green C-H cyanation of terminal alkynes

This study describes a benign C-H cyanation of terminal alkynes with α-cyanoesters serving as a nontoxic cyanide source. In situ generation of the key copper cyanide intermediate is proposed by a sequence of α-C-H oxidation and copper-mediated β-carbon elimination of α-cyanoesters, releasing the α-ketoester byproduct observed experimentally. The ensuing reaction of copper cyanide with terminal alkynes delivers preferentially cyanoalkynes and surpasses the possible Glaser type dimerization of terminal alkynes or the undesired accumulation of HCN under protic conditions. The presence of the co-oxidant K2S2O8 is crucial to this selectivity, probably by promoting oxidative transmetalation and the resulting formation of the Cu(iii)(acetylide)(CN) intermediate. All the reagents and salts used are commercially available, cheap and nontoxic, avoiding the use of highly toxic cyanide salts typically required in cyanation studies. The scope of this reaction is demonstrated with a set of alkynes and α-cyanoesters. The application of this method to late-stage functionalization of the terminal alkyne group in an estrone derivative is also feasible, showing its practical value for drug design.

Chemo- And regioselective click reactions through nickel-catalyzed azide-alkyne cycloaddition

Metal-catalyzed cycloaddition is an expeditious synthetic route to functionalized heterocyclic frameworks. However, achieving reactivity-controlled metal-catalyzed azide-alkyne cycloadditions from competing internal alkynes has been challenging. Herein, we report a nickel-catalyzed [3 + 2] cycloaddition of unsymmetrical alkynes with organic azides to afford functionalized 1,2,3-triazoles with excellent regio- and chemoselectivity control. Terminal alkynes and cyanoalkynes afford 1,5-disubstituted triazoles and 1,4,5-trisubstituted triazoles bearing a 4-cyano substituent, respectively. Thioalkynes and ynamides exhibit inverse regioselectivity compared with terminal alkynes and cyanoalkynes, affording 1,4,5-trisubstituted triazoles with 5-thiol and 5-amide substituents, respectively. Density functional theory calculations are performed for the elucidation of the reaction mechanism. The computed mechanism suggests that a nickellacyclopropene intermediate is generated by the oxidative addition of the alkyne substrate to the Ni(0)-Xantphos catalyst, and the subsequent C-N coupling of this intermediate with an azide is responsible for the chemo- and regioselectivity.

Palladium-Catalyzed Nitrile-Assisted C(sp3)-Cl Bond Formation for Synthesis of Dichlorides

A palladium-catalyzed coupling procedure of alkenes with alkynylnitriles has been demonstrated for the synthesis of dichlorides. The reaction is the first example of nitrile-assisted C(sp3)-Cl formation promoted by coordination of a cyano group with an alkylpalladium(II) complex. The construction of a five-membered cycle intermediate successfully inhibits the β-hydride abstraction, resulting in direct C-Cl bond reductive elimination of alkylpalladium(II) chloride.

The synthesis of 3-amino-5-arylisothiazoles from propynenitriles

A new synthesis of 3-amino-5-arylisothiazoles is reported. The reaction is operationally simple, utilises readily synthesised propynenitriles as starting materials and is tolerant of a range of functional groups. The optimised reaction conditions can also be used with 3-chloropropenenitriles in place of propynenitriles.

Silver-Mediated Direct C-H Cyanation of Terminal Alkynes with N-Isocyanoiminotriphenylphosphorane

A direct cyanation of terminal alkynes for the synthesis of propionitrile derivatives, with the aid of silver salt using water additive, has been achieved. The cyano source used is N-isocyanoiminotriphenylphosphorane, which is nontoxic, safe, and easy to handle. This protocol is characterized by its operational simplicity, high efficiency with excellent yields, broad substrate scope, and greater functional group tolerance.

Cyclopentadienones as intermediates for the synthesis of highly functionalized biaryls

A new approach to the synthesis of substituted biaryls, via Diels-Alder reaction between cyclopentadienones and arylacetylenes, is described.