Process-Controlled Regiodivergent Copper-Catalyzed Azide–Alkyne Cycloadditions: Tailor-made Syntheses of 4- and 5-Bromotriazoles from Bromo(phosphoryl)ethyne
Yasuhiro Okuda, Kazuto Imafuku, Yoshiyuki Tsuchida, Tomoyo Seo, Haruo Akashi, Akihiro Orita
Abstract
We developed a regiodivergent syntheses of 4- and 5-bromo-substituted 1,2,3-triazoles in copper-catalyzed azide–alkyne cycloadditions (CuAACs) by taking advantage of bromo(phosphoryl)ethyne 1 as a bromoethyne equivalent. A one-shot dephosphorylative CuAAC of 1 afforded 4-bromotriazoles, which was transformed into a histone deacetylase 8 (HDAC8)-selective inhibitor, NCC-149. However, the direct CuAAC catalyzed by CuI/Cu(OAc)2 provided 5-bromo-4-phosphoryltriazoles. The consecutive nucleophilic substitution of the bromo group with thiols followed by MeOK-promoted dephosphorylation gave 5-thio-substituted triazoles.
Topics & Concepts
ChemistryAlkyneCatalysisAzideCombinatorial chemistryCopperCycloadditionProcess (computing)Organic chemistryComputer scienceOperating systemClick Chemistry and ApplicationsCatalytic C–H Functionalization MethodsChemical Synthesis and Analysis