Nickel-Catalyzed Azide–Alkyne Cycloaddition To Access 1,5-Disubstituted 1,2,3-Triazoles in Air and Water

Transition-metal-catalyzed or metal-free
azide–alkyne cycloadditions
are methods to access 1,4- or 1,5-disubstituted 1,2,3-triazoles. Although
the copper-catalyzed cycloaddition to access 1,4-disubstituted products
has been applied to biomolecular reaction systems, the azide–alkyne
cycloaddition to access the complementary 1,5-regioisomers under aqueous
and ambient conditions remains a challenge due to limited substrate
scope or moisture-/air-sensitive catalysts. Herein, we report a method
to access 1,5-disubstituted 1,2,3-triazoles using a Cp2Ni/Xantphos catalytic system. The reaction proceeds both in water
and organic solvents at room temperature. This protocol is simple
and scalable with a broad substrate scope including both aliphatic
and aromatic substrates. Moreover, triazoles attached with carbohydrates
or amino acids are prepared via this cycloaddition.

过渡金属催化或无金属参与的叠氮-炔烃环加成反应，是合成1,4-或1,5-二取代1,2,3-三氮唑的方法。尽管用于制备1,4-二取代产物的铜催化环加成反应已应用于生物分子反应体系，但在水相及常温条件下合成对应1,5-区域异构体的叠氮-炔烃环加成反应仍面临挑战——现有方法或底物适用范围狭窄，或所用催化剂对水分与空气敏感。本文报道了一种采用二(环戊二烯基)镍(Cp₂Ni)/Xantphos催化体系合成1,5-二取代1,2,3-三氮唑的方法。该反应可在水相及有机溶剂中于室温下进行，操作简便且可规模化，底物适用范围广泛，涵盖脂肪族与芳香族底物。此外，通过该环加成反应还可制备连有碳水化合物或氨基酸的三氮唑衍生物。