Triazoles 1,4-disubstituted, selective synthesis

Tsai CW, Yang SC, Liu YM et al (2009) Microwave-assisted cycloadditions of 2-alkynylbenzonitriles with sodium azide selective synthesis of tetrazolo[5,l-a]pyridines and 4,5-disubstituted-2//-l,2,3-triazoles. Tetrahedron 65 8367-8372... 

Shun-Yi Wang et al. disclosed a novel synthetic approach toward 1,5-disubstituted 1,2,3-triazoles 141 and 1,4-disubstituted 1,2,3-triazoles 142 by aerobic oxidative cycloaddition of a-chlorotosylhydrazone 140 with primary aryl amine 113 (Scheme 4.57) [56]. Significantly, the reaction proceeded smoothly to alford 1,4-disubstituted 1,2,3-triazoles 142 and 1,5-disubstituted 1,2,3-triazoles 141 under catalyst-free, metal-free, azide-free, and peroxide-free conditions. Strikingly, this transformation provided selective synthesis of both regioisomers of 1,2,3-triazoles. 

As 1,4-disubstituted 1,2,3-triazoles are usually prepared through copper-catalyzed 1,3-dipolar cycloadditions of terminal alkynes with organic azides, the use of a single copper complex for a direct arylation-based sequential catalysis was probed. Thereby, a modular chemo- and regioselective synthesis of fully-substituted 1,2,3-triazoles was achieved (Scheme 9.43). Notably, the overall reaction involved the selective coupUng of four components through the formation of one C—C- and three C—N-bonds [58]. 

Abstract Although the synthesis of 1,4- or 1,5-disubstituted 1,2,3-triazoles has been popularized by the recent developments of metal-catalyzed 3-1-2 cycloaddition of organic azides and terminal alkynes, the preparation of 1,4,5-trisubstituted triazoles is less popular. The focus of this chapter is the synthesis of these heterocycles, using condensation reactions and rearrangements, selective preparation of trisubstituted triazoles from disubstituted precursors, and formal [3-1-2] cycloaddition reactions involving internal alkynes. 

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