Synthesis of 1,5-Diaryl-1,2,3-triazoles Under Transition-Metal-Free Conditions

Significance

Reported is the synthesis of 1,5-diaryl-substituted 1,2,3-triazoles 3 from aryl azides 1 and terminal alkynes 2 under transition-metal-free conditions. The nucleophilic acetylide intermediate, prepared from terminal alkynes (S. Saito and co-workers J. Org. Chem. 2003, 68, 3702) without aggressive lithium or magnesium reagents, undergoes the reaction selectively with even modestly electrophilic organic azides producing 1,5-disubstituted triazoles 3. After screening of various hydroxide and alkoxide bases, the shorter reaction time and the experimental convenience of using aqueous base solution led to NMe₄OH as the advantageous catalyst for practical reasons. Most aryl and heteroaryl azides and terminal alkynes participate in the 1,5-diaryl-substituted 1,2,3-triazoles 3 synthesis. Aryl azides with sterically demanding ortho substituents gave lower yields of products. Moreover, electronic properties of both reactants influence the outcome of the reaction significantly. Thus, 2 and 3 with EWGs reduce the nucleophilicity of the acetylide anion and the efficient triazenide cyclization step. Alkyl acetylenes failed to react under this condition due to their lower acidity.