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Synthesis of Multisubstituted 1,2,3-Triazoles: Regioselective Formation and Reaction Mechanism

Tzu-Ching Chi, Po‐Chun Yang, Shao-Kang Hung, Hui‐Wen Wu, Hong-Chi Wang, Hsin‐Kuan Liu, Liwen Liu, Ho‐Hsuan Chou

2024The Journal of Organic Chemistry21 citationsDOIOpen Access PDF

Abstract

A synthetically useful approach to functionalized triazoles is described via the reaction of β-carbonyl phosphonates and azides. 1,4- and 1,5-disubstituted and 1,4,5-trisubstituted triazoles can be regio- and chemoselectively accessed under mild conditions in good to excellent yields (31 examples, up to 99%). A mechanism is proposed that rationalizes the avoidance of the 4-phosphonate byproducts, which is aligned with crystallographic and experimental evidence.

Topics & Concepts

ChemistryRegioselectivityPhosphonateCombinatorial chemistryMechanism (biology)Reaction mechanismReaction conditionsComputational chemistryStereochemistryOrganic chemistryCatalysisEpistemologyPhilosophyClick Chemistry and ApplicationsChemical Synthesis and AnalysisHIV/AIDS drug development and treatment