ORGN 131

Copper(I)- and ruthenium(II)-catalyzed cycloadditions of azides and alkynes provide ready access to N-1 substituted 1,2,3-triazoles. In contrast, a general method for the synthesis of the N-2 substituted 1,2,3-triazole isomers is not available. Herein, we describe a new, straight-forward three-component reaction, whereupon an alkyne, sodium azide, and formaldehyde undergo a copper(I)-catalyzed cycloaddition to yield N-2 hydroxymethyl-substituted 1,2,3-triazoles in good to excellent yield (67-95%). These compounds can be modified in a variety of ways, including the synthesis of a versatile intermediate, N-2 chloromethyl 1,2,3-triazole. Furthermore, three complementary methods for the removal of the hydroxymethyl group have been developed, leading to unsubstituted, NH-1,2,3-triazoles, an important class of pharmacophores.