Exploiting the umpolung reactivity of diazo groups: direct access to triazolyl-azaarenes from azaarenes

Abstract

Facile access to 4,3-fused 1,2,4-triazolyl-isoquinolines, pyridines and phenanthridines is achieved through electrophilic diazomethylation of the azaarenes with hypervalent iodine diazo reagents followed by 1,5-cyclization of the resulting ammonium diazonium ylides.

α-Diazo-λ3-iodanes and α-diazo sulfonium salts: the umpolung of diazo compounds

“…24 Also in the same year Rastogi and coworkers published a base assisted synthesis of [1,2,4]triazolo[4,3-a]pyridines 35, by reaction of 4 with pyridines and isoquinolines (Scheme 8). 25 Intermediates in this reaction are a-diazoalkyl pyridinium salts (Int-IV); compounds already described by Weiß in his seminal work. 11 Treatment of these species with base result in the deprotonation of the iminium moiety and subsequent cyclization towards the desired heterocycles.…”

“… 11 Treatment of these species with base result in the deprotonation of the iminium moiety and subsequent cyclization towards the desired heterocycles. 25 A variant of this reaction, but using piperidines and tetrahydroisoquinolines as the nucleophilic reaction partner has been very recently reported by Singh and coworkers. 26 …”

Synthesis of Hypervalent Iodine Diazo Compounds and Their Application in Organic Synthesis

“…[64] In 2022, a series of 1,2,4-triazoles 43, 45 and 47 were obtained from the [2 + 3] cascade annulation of tetrahydroisoquinolines 42 or azaarenes (44 or 46) with diazomethyl-substituted iodine(III) compounds 3 a-c or 3 h (Scheme 15). [65,66] These conversion methods were achieved through nucleophilic reactions to construct C(sp 2 )À N bonds, however the process was not the same. For example, diazomethyl-substituted iodine(III) compound was nucleophilic attacked by tetrahydroisoquinoline or azaarene to generate intermediates A and D, respectively.…”

“…[65] The [3 + 2]-dipolar cycloaddition between azaarenes (44 or 46) and compounds (3 a or 3) in the presence of Na 2 CO 3 afforded 1,2,4-triazolyl azaarenes 45 and 47 in 37-71 % and up to 69 % yields, respectively. [66] Diazirines containing two nitrogen atoms in ternary heterocycles have been widely used as intermediates for carbene generation and can release nitrogen under appropriate conditions of exposure. [67] In addition, diazirines also had extensive applications in photoaffinity labelling.…”

“…The experimental results showed that various tetrahydroisoquinolines 42 bearing electron‐withdrawing and electron‐donating aryl groups as well as a methyl group at the alkyl linker afforded the corresponding 1,2,4‐triazolo[3,4‐a]isoquinolines 43 in 62–78 % yields [65] . The [3+2]‐dipolar cycloaddition between azaarenes ( 44 or 46 ) and compounds ( 3 a or 3 ) in the presence of Na 2 CO 3 afforded 1,2,4‐triazolyl azaarenes 45 and 47 in 37–71 % and up to 69 % yields, respectively [66] …”