Cu^II‐Catalyzed Oxidative Formation of 5‐Alkynyltriazoles

Abstract

In an alcoholic solventu nder the catalysis of Cu(OAc) 2 ·H 2 O, organic azide and terminal alkyne could oxidatively couple to afford 5-alkynyl-1,2,3-triazole (alkynyltriazole) at room temperature under an atmosphere of O 2 in a few hours. The involvemento f1 ,5-diazabicyclo[4.3.0]non-5ene (DBN) is essential, withoutw hich the redoxn eutral coupling insteadp roceeds to produce 5-H-1,2,3-triazole (protiotriazole) as the major product. Therefore, DBN switches the redox neutralc oupling between terminal alkyne and organic azide, the copper-catalyzed "click" reaction to afford protio-triazole, to an oxidation reaction that resultsi na lkynyltriazole. The organic base DBN is effective in accelerating the copper(II)-catalyzed oxidation of terminal alkyne or copper(I) acetylide, whichi si ntercepted by an organic azide to produce alkynyltriazole. The proposed mechanistic model suggests that the selectivity between alkynyl-and protiotriazole, and other acetylide or triazolide oxidation products is determined by the competition between copper(I)-catalyzed redox neutral cycloadditiona nd copper(II)/O 2 -mediated acetylide oxidation after the formationo fc opper(I) acetylide.Scheme1.Copper-catalyzed azide-alkyne cycloaddition under redox neutral or oxidative conditions( [a] TBTA = tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine, al igand known for accelerating copper-catalyzed triazole ring formation from azide and terminalalkyne. [5] ).

Each Interruption is an Opportunity: Novel Synthetic Strategies Explored Through Interrupted Click Reactions

“…For the reaction to proceed to completeness, the presence of oxygen and the base DBN is necessary (Scheme 62). [69] 1,2,3-Triazole-fused imidazo-[1,2-a]pyridines 175 are obtained through an intramolecular Ullmann reaction between sodium azide, terminal alkynes, and 3-bromo-2-(2bromophenyl)imidazo[1,2-a]pyridines 174 (Scheme 63). We have to remark that the reaction conditions (strong base, high temperature) may also favor CH functionalization rather than an interrupted click reaction.…”

“…For the reaction to proceed to completeness, the presence of oxygen and the base DBN is necessary (Scheme 62). [69] …”