Silver(i) catalyzed intramolecular cyclization of N-(2-(alk-1-yn-1-yl))-1H-tetrazoles leading to the formation of N-cyano-2-substituted indoles under ambient conditions

Abstract

Synthesis of N-heterocycles from N-(2-(alk-1-yn-1-yl))tetrazoles to obtain N-cyano 2-substituted indoles as selective products.

Synthesis and X-ray Crystal Structure of N’-Cyano-N,N’-dimethyl-4-nitrobenzohydrazide

“…The cyano group is almost linear (N2-C3-N3: 176.5 • ). The slightly bended orientation of the two nitrogen atoms attached to the cyano carbon is in agreement with structural observations for other cyanohydrazines [10,11] and N,N-disubstituted cyanamides in general (see the crystal structures published in [19,20] for example). In contrast to the finding for Compound 2, the out-of-plane angles for the N β atoms in N α ,N β -dialkylated (thio)semicarbazides (II-IV, Table 3) are significantly smaller, which in turn indicates a more sp 2 -like hybridization state for these nitrogen atoms.…”

Recent advances in the synthesis of indoles from alkynes and nitrogen sources

“…A similar route was also used to describe the preparation of N-cyano-2-substituted indoles 218 using 2-aryltetrazole alkynes as the starting material in a silver(I) catalyzed intramolecular cyclization (Scheme 256). 289 The advance of the methodology is the identification of a cyclopropyl argentium cationic intermediate 217, which could be responsible for the use of a catalytic amount of the silver salt.…”

Indole Synthesis Using Silver Catalysis

“…In view of the importance of 2-substitutedi ndoles in medicinal applications,afacile silver-catalyzed route towards Ncyano-2-substitutedi ndole derivatives was developed by Trivedi et al andr eportedi n2 017. [28] Hydroamination reactions commonlyu se o-alkynylanilines as starting substrates for indole formation but, in contrast, Trivedi and co-workers utilized au nique intramolecular cyclization of alkynyl tetrazoles 75 instead, whichwas catalyzed by AgOAc under ambient conditions (Scheme 25). Lineara lkyl,c ycloalkyl and aryl substituted alkynes are tolerated in the startingt etrazoles 75,w ith this methodu sed to prepare ar ange of 2/7-substituted N-cyanoindoles 76 in high yields.…”