Cu(I)-azidopyrrolo[3,2-d]pyrimidine Catalyzed Glaser–Hay Reaction under Mild Conditions

Abstract

The limitation of the CuAAC "click" reaction with a 2-azidopyridine substrate, owing to its equilibrium with a tetrazole isomer, is exploited herein for its utility in the Glaser−Hay reaction. A catalytic combination of a 2-azidopyridine analogue, 4azido-5H-pyrrolo[3,2-d]pyrimidine, and CuI afforded homocoupled products of terminal alkynes, without any trace of triazole product, under mild conditions with a broad substrate scope. Emphasis on carbohydrate-based substrates appended to a propargylic group led to 1,3-diynes in good to excellent yields.

A Simple and Practical Bis-N-Heterocyclic Carbene as an Efficient Ligand in Cu-Catalyzed Glaser Reaction

“…With regard to our results, the reaction mechanism is not fully understood at present. After referring to a lot of the relevant literature [ 14 , 24 , 25 , 40 , 43 , 46 ], we proposed that this Cu-catalyzed Glaser homocoupling might take place as shown in Scheme 5 , which possibly involves the typical Glaser reaction steps. According to our assumptions, halogen bromide anions perhaps act as Lewis bases which have a weak ability to deproton in this catalysis system.…”

“…16, 119.18, 81.71, 73.61, 29.06, 15.37. 1,4-bis(4-propylphenyl)buta-1,3-diyne (2f) [43]. White solid.…”

“…Very recently, Tiwari and co-workers [ 25 ] reported a benzotriazole ligand for the cross-coupling of terminal alkynes catalyzed by CuI in the presence of K 2 CO 3 . Lankalapalli and co-workers, using a catalytic combination of a 2-azidopyridine analogue, 4-azido-5H-pyrrolo [3,2-d]pyrimidine, and CuI, afforded homocoupled products of terminal alkynes [ 43 ]. However, it usually needs a stoichiometric amount of copper salts, excess oxidants, rigid inorganic bases, and high temperature to afford low to moderate yields for aliphatic diynes.…”

Efficient Ru-Catalyzed Electrochemical Homo- and Heterocoupling Reaction of Terminal Alkynes: Synthesis, In Vitro Anticancer Activity, and Docking Study

“…The straightforward synthesis of homocoupled 1,3-diynes was reported by Glaser–Eglinton–Hay–Cadiot–Chodkiewicz with adequate results. − In the standard synthesis of 1,3-diynes, copper is assigned to be an outstanding catalyst. − Apart from that, some bimetallic metal additives with copper were used for the preparation of 1,3-diynes from different alkyne sources. − In addition to that, some nanocomposites, − charge-transfer catalysts, and visible light-induced , reaction media acted as active catalysts to afford these diyne building blocks. Likewise, there are numerous methodologies that exist in the literature for the synthesis of 1,3-diyne moieties. − However, the push for this methodology is still continuing and under strong consideration by various academia along with pharmaceutical industries. Some years ago, Stelzer and co-workers reported a complex ruthenium-catalyzed homocoupling reaction for terminal acetylenes .…”

“…Likewise, there are numerous methodologies that exist in the literature for the synthesis of 1,3-diyne moieties. 49 − 52 However, the push for this methodology is still continuing and under strong consideration by various academia along with pharmaceutical industries. Some years ago, Stelzer and co-workers reported a complex ruthenium-catalyzed homocoupling reaction for terminal acetylenes.…”