Asymmetric Organocatalytic Approach to 2,4-Disubstituted 1,2,3-Triazoles by N2-Selective Aza-Michael Addition

Despite the fact that N1-functionalization of NH-1,2,3-triazoles has been known for several decades, enantioselective variants of this reaction have only recently been developed. Nevertheless, functionalization at the N2-position of NH-1,2,3-triazoles leading to optically active N2-substituted triazoles is not yet developed. In this article, we report, for the first time, the asymmetric aza-Michael reaction of 4-aryl-NH-1,2,3-triazoles to cyclic enones under the catalytic influence of chiral bifunctional thiourea organocatalysts for the enantioselective generation of 2,4-disubstituted 1,2,3-triazoles. The cinchonine-derived thiourea catalyst III worked efficiently in the current transformation to produce N2-functionalized 1,2,3-triazoles as major products in optical yields up to >99.9% along with minor 1,4-disubstitued 1,2,3-triazoles.

尽管NH-1,2,3-三氮唑（NH-1,2,3-triazoles）的N1位官能化反应已为学界所知数十年之久，但其对映选择性变体仅在近年才得以开发。然而，针对NH-1,2,3-三氮唑N2位进行官能化以制备具有光学活性的N2取代三氮唑的方法，迄今仍未被报道。在本文中，我们首次报道了在手性双功能硫脲有机催化剂的催化作用下，4-芳基-NH-1,2,3-三氮唑与环状烯酮发生不对称氮杂-Michael（aza-Michael）反应，实现2,4-二取代1,2,3-三氮唑的对映选择性合成。其中，源自辛可宁的硫脲催化剂III可高效催化该转化，以最高超过99.9%的光学产率得到主要产物N2官能化1,2,3-三氮唑，同时伴随少量1,4-二取代1,2,3-三氮唑生成。