Making endo-cyclizations favorable again: a conceptually new synthetic approach to benzotriazoles via azide group directed lithiation/cyclization of 2-azidoaryl bromides. Issue 18 (17th April 2019)

• Record Type: Journal Article
• Authors: Ageshina, Alexandra A.; Chesnokov, Gleb A.; Topchiy, Maxim A.; Alabugin, Igor V.; Nechaev, Mikhail S.; Asachenko, Andrey F.
• Is Part Of: Organic & biomolecular chemistry. Volume 17:Issue 18(2019)
• Page Start: 4523
• Page End: 4534
• Publication Date: 2019-04-17
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c9ob00615j
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Practical alternative to the synthesis of benzotriazoles via bridging of two ortho-amino groups with an electrophilic nitrogen atom was developed. Abstract : Although benzotriazoles are important and ubiquitous, currently there is only one conceptual approach to their synthesis: bridging the two ortho -amino groups with an electrophilic nitrogen atom. Herein, we disclose a new practical alternative – the endo -cyclization of 2-azidoaryl lithiums obtained in situ from 2-azido-aryl bromides. The scope of the reaction is illustrated using twenty-four examples with a variety of alkyl, alkoxy, perfluoroalkyl, and halogen substituents. We found that the directing effect of the azide group allows selective metal–halogen exchange in aryl azides containing several bromine atoms. Furthermore, (2-bromophenyl)diazomethane undergoes similar cyclization to give an indazole. Thus, cyclizations of aryl lithiums containing an ortho –X = Y = Z group emerge as a new general approach for the synthesis of aromatic heterocycles. DFT computations suggested that the observed endo -selectivity applies to the anionic cyclizations of other functionalities that undergo "1, 1-additions" ( i.e., azides, diazo compounds, and isonitriles). In contrast, cyclizations with the heteroatomic functionalities that follow the "1, 2-addition" pattern (cyanates, thiocyanates, isocyanates, isothiocyanates, and nitriles) prefer the exo -cyclization path. Hence, such reactions expand the current understanding of stereoelectronic factors in anionic cyclizations.