Copper(II)-Catalyzed C–H Nitrogenation/Annulation Cascade of Ketene N,S-Acetals with Aryldiazonium Salts: A Direct Access to N²-Substituted Triazole and Triazine Derivatives

Abstract

Direct synthesis of N 2 -substituted triazole and triazine derivatives has been a challenge in N-heterocyclic chemistry. Under copper(II) catalysis ketene N,S-acetals, that is, alkylthio-substituted enaminones, efficiently reacted with aryldiazonium salts to allow the regioselective generation of functionally diverse N 2 -substituted 1,2,3-triazoles and 2,3dihydro-1,2,4-triazines. The oxidant and base-dependent reaction yielded the fiveand six-membered N-heterocyclic products, respectively. The synthetic protocol features broad substrate scopes and good functional group tolerance under mild conditions. The mechanistic studies have revealed that the reaction proceeds via alkenyl azo/imino hydrazone intermediates.N -Heterocyclic compounds have been demonstrated to have versatile applications in pharmaceuticals, agrochemicals, functional materials, and coordination chemistry, 1 among which 1,2,3-triazole and 1,2,4-triazine derivatives have shown diverse anticancer, antibacterial, antiepileptic, and antiviral activities (Scheme 1). 2 Due to their potential

Recent Advances in the Synthesis of Nitrogen Heterocycles Using Arenediazonium Salts as Nitrogen Sources

“…In 2020, Yu and co-workers disclosed a new procedure for the construction of N 2 -aryl-1,2,3-triazoles through a Cu(II)-catalyzed CÀ H nitrogenation/ annulation cascade of alkylthio-enaminones with aryldiazonium salts (Scheme 23). [36] The optimized reac- tion conditions for the synthesis of 1,2,3-triazoles were: the molar ratio of alkylthio-enaminones:aryldiazonium salts = 1:2, 30 mol% CuCl 2 as the catalyst, 1.0 equiv. of K 2 S 2 O 8 as the oxidant, 0.5 equiv.…”

“…A novel protocol for the construction of N 2 -arylsubstituted 2,3-dihydro-1,2,4-triazines from benzylamine-derived ketene N,S-acetals and aryldiazonium salts was reported by Yu and co-workers (Scheme 33). [36] The optimized reaction conditions for the synthesis of triazines from β-enaminones and aryl diazonium salts (Scheme 34). [44] The reaction of aryl diazonium salts with differently substituted β-enaminones was carried out using 20 mol% CuBr 2 as the catalyst and 2.0 equiv.…”

“…A novel protocol for the construction of N 2 ‐aryl‐substituted 2,3‐dihydro‐1,2,4‐triazines from benzylamine‐derived ketene N , S ‐acetals and aryldiazonium salts was reported by Yu and co‐ workers (Scheme 33). [36] The optimized reaction conditions for the synthesis of N 2 ‐aryl‐substituted 2,3‐dihydro‐1,2,4‐triazines were: the molar ratio of ketene N , S ‐acetals:aryldiazonium salts=1:2, 30 mol% CuCl 2 as the catalyst, 0.5 equiv. of K 2 S 2 O 8 as the oxidant, 3.0 equiv.…”

Aryl DiazoniumSalt‐TriggeredCyclization and Cycloaddition Reactions: Past, Present, and Future

“…an intermolecular addition and cyclization reaction of aryl diazonium salts with ketene N,S ‐acetals (Scheme 7). [ 75 ] Under the catalysis of CuCl 2 , the reaction of various aryl diazonium salts 30 and ketene N,S ‐acetals 29 proceeded smoothly to deliver a diverse collection of highly substituted 3 H ‐1,2,4‐triazines 31 in moderate to good yields (30%—77%). It was found that the imino hydrazone 32 could be an important intermediate in this reaction, and oxidant is necessary to regenerate the copper(II) catalyst after the reductive elimination of the seven‐membered cyclic hydrazone complex 33 .…”

“…with aryl diazonium salts 30 (Scheme 33). [ 75 ] In the presence of CuCl 2 catalyst, alkylthio‐substituted enaminones 131 reacted with aryl diazonium ion via cyclization, benzyl elimination, and reductive elimination to afford a wide range of highly functionalized keto‐ and alkylthio‐subsituted N 2 ‐aryl 1,2,3‐triazoles 132 . K 2 S 2 O 8 and molecular oxygen behaved as oxidant to convert the proposed Cu(0) to Cu(II) catalyst for subsequent catalytic cycles.…”