Implanting Nitrogen into Hydrocarbon Molecules through CH and CC Bond Cleavages: A Direct Approach to Tetrazoles

Abstract

The development of novel methods for the preparation of tetrazoles is of long-standing interest and a challenge for organic chemists because of the importance of these compounds in chemistry and biology. In particular, 1,5-disubstituted tetrazoles are very useful compounds in medicinal chemistry and important synthetic intermediates. In the past several decades, some general strategies for the synthesis of 1,5-disubstituted tetrazoles from functionalized starting materials have been developed (Scheme 1). These methods include: a) the reactions of ketones or oximes with sodium azide and hydrogen azides, b) the reactions of amides with sodium azides in the presence of phosphorus(V) chloride or triflic anhydride and the reactions of amidrazones with dinitrogen tetroxide or nitrous acid, c) the reactions of imidoyl chlorides or imidoylbenzotriazoles with sodium azides and, d) the reactions of nitriles with alkyl azides. These developed methods significantly improved the synthesis of tetrazoles, but these approaches have some limitations, such as the use of protic acid catalysts, tedious workups, and the use of functionalized starting materials, hence encouraging scientists to discover new strategies. The direct transformation of hydrocarbon molecules by transition-metal-catalyzed selective C H and C C bond activation (cleavage) has attracted considerable attention, owing not only to its fundamental scientific appeal but also to its potential utility in organic synthesis. A direct approach to tetrazoles through C H and C C bond cleavages of simple hydrocarbon molecules is still an extremely attractive yet challenging goal. Herein, we demonstrate a novel and efficient Cu-promoted implanting of nitrogen into simple hydrocarbon molecules to construct 1, 5-disubstituted tetrazoles through C H and C C bond cleavages, and C N bond formation under mild and neutral reaction conditions (Scheme 1e). Azide has been widely used as a useful aminating reagent in organic synthesis. The application of azides for the direct synthesis of aryl nitriles and alkenyl nitriles through C H bond cleavage has been recently reported. Recent achievements on the functionalization of C H and C C bonds encouraged us to try the direct synthesis of