Pyridyl Glycosyl Triazole/CuI-Mediated Domino/Tandem Synthesis of Quinazolinones

Abstract

The glycosyl 1,2,3-triazoles are expediently accessible from readily available sugar-derived glycosyl azide by utilizing modular CuAAC "Click Chemistry", and the resulting glycohybrid skeleton possesses efficient metal-coordinating centers that support a wide range of metal-mediated efficient catalysis in various imperative organic transformations. Here, we designed and developed pyridyl glycosyl triazoles by employing the CuAAC reaction of D-glucose-derived glycosyl azides and alkynyl pyridines. These pyridyl glycosyl triazoles with Cu(I) salt were explored as an efficient catalyst to successfully assemble 2-amino-3-substituted and 3-substituted quinazolinones by the domino/tandem cross-coupling reaction of various N-substituted o-halobenzamides with cyanamide and formamide, respectively. The devised protocol has some notable features, including biocompatibility, low cost, easily accessible starting materials for the glycosyl ligands, high yield, broad spectrum, low catalytic loading, and mild reaction conditions.

Triazole-Appended Glycohybrid/CuI-Catalyzed C–C Cross-Coupling of Aryl/Heteroaryl Halides with Alkynyl Sugars

“…The glycosyl triazole ligands L1−L5 were synthesized from readily available D-glucose as described in our previous work. 31,43 Ligand L6 was synthesized from D-glucose diacetonide 1, 48 which was on 3-O-benzylation using benzyl bromide in the presence of NaH followed by selective opening of 5,6-isopropylidene using 70% acetic acid furnished the glycosyl diol 2. 49,50 The resulting glycosyl diol 2 on sodium periodate-assisted oxidation followed by standard reduction of aldehyde functionality gave the respective glycosyl alcohol 3.…”

“…Our synthetic strategy began with the development of the designed sugar-based ligands shown in Figure . The glycosyl triazole ligands L1–L5 were synthesized from readily available d -glucose as described in our previous work. , Ligand L6 was synthesized from d -glucose diacetonide 1 , which was on 3- O -benzylation using benzyl bromide in the presence of NaH followed by selective opening of 5,6-isopropylidene using 70% acetic acid furnished the glycosyl diol 2 . , The resulting glycosyl diol 2 on sodium periodate-assisted oxidation followed by standard reduction of aldehyde functionality gave the respective glycosyl alcohol 3 . The resulting alcohol 3 was then subjected to selective tosylation using tosyl chloride in the presence of base followed by azidation using NaN 3 resulting in a high yield of the glycosyl azide 4 , , that was on regioselective CuAAC click reaction with 4-ethynyl- N , N -dimethylaniline afforded the glycosyl triazole L6 (Scheme ).…”

“…Ma's group reported a series of potential ligands that efficiently support Cu-catalysis. − In addition to existing ligands, the application of sugar-based molecules as ligands and catalysts is ever expanding; , however, it is yet limited in these coupling reactions. The natural abundance, chirality, molecular architecture, and multiple binding sites associated with the carbohydrate molecules aid them as a suitable scaffold for the synthesis of metal–ligand systems and organocatalysts. ,, The sugar-derived ligands, such as glycosylated 1,2,3-triazoles or triazole-appended glycohybrids, have an increasing impact on metal-catalyzed coupling reactions. − Interestingly, carbohydrate-containing 1,2,3-triazoles obtained via a regioselective Cu-catalyzed azide–alkyne cycloaddition (CuAAC) modular tool have displayed enormous applications in various emerging fields ranging from medicinal chemistry to catalysis. − Herein, we explored the regioselective CuAAC protocol and developed novel 1,2,3-triazole-appended glycohybrids and screened them as ligands with monotriazolyl and bis-triazolyl rings for the Cu-catalyzed Sonogashira reaction in order to explore their efficient metal-coordinating properties. We are delighted to disclose that these biocompatible triazole ligands were enormously effective in assembling various glycohybrids including glycosyl rods in high-to-excellent yields via the Sonogashira cross-coupling reaction of alkynyl sugar with various aryl/heteroaryl substrates at 120 °C.…”

Copper-catalyzed synthesis of quinazolines via cascade cyclization/hydrodehalogenation

“…The reaction commences with the formation of the first Cu( iii ) intermediate I through an oxidative addition reaction of the C–Br bond of 2-bromobenzaldehyde ( 1a ) to the CuI. 23 Afterward, intermediate I on transmetalation with the Cu( i ) salt of acetamide gives Cu-complex II . 23 d The Cu-complex II undergoes reductive elimination to afford the N -arylation product III , 23 d ,24 which further experiences hydrolysis to produce IV in the presence of H 2 O and base.…”

TMSOTf‐Promoted Synthesis of Quinazolin‐4(3H)‐one Utilizing DMSO as a Carbon Source

“…[10] In 2022, Tiwari et al described the pyridyl glycosyl triazole L1 assisted synthesis quinazolin-4(3H)-ones by the reaction of 2-halobenzamide with formamide in the presence of copper (I) iodide. [11] Very recently, Wu et al described the synthesis of quinazolin-4(3H)-one using 2-amino-N-substituted benzamide, DMSO in presence of NH 4 I as a catalyst and TBHP as an oxidant. [12] However, these synthetic methods suffer from severe limitations such as the use of transition metal, longer reaction time, harsh reaction conditions, use of toxic solvents, and multistep synthesis to access the starting materials.…”