Collect. Czech. Chem. Commun. 2007, 72, 1014-1024

Improved Protocols for Microwave-Assisted Cu(I)-Catalyzed Huisgen 1,3-Dipolar Cycloadditions

Pedro Cintasa, Katia Martinab, Bruna Robaldob, Davide Garellab, Luisa Boffab and Giancarlo Cravottob,*

a Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Extremadura, Avenida de Elvas s/n, E-06071 Badajoz, Spain
b Dipartimento di Scienza e Tecnologia del Farmaco, Università di Torino, Via P. Giuria 9, I-10125 Torino, Italy


The Huisgen 1,3-dipolar cycloaddition of azides and acetylenes catalyzed by Cu(I) salts, leading to 1,2,3-triazoles, is one of the most versatile "click reactions". We have developed a series of optimized protocols and new applications of this reaction starting from several substrates, comparing heterogeneous vs homogeneous catalysis, conventional heating vs microwave irradiation or simultaneous microwave/ultrasound irradiation. Both non-conventional techniques strongly promoted the cycloaddition (bromide → azide → triazole), that could be conveniently performed in a one-pot procedure. This was feasible even with such bulky molecules as functionalized β-cyclodextrins (β-CD), starting from 61-O-tosyl-β-CD or from heptakis[6-O-(tert-butyldimethylsilyl)]-21-O-propargyl-β-CD. "Greener" heterogeneous catalysis with charcoal-supported Cu(II) or Cu(I) (prepared under ultrasound) was advantageously employed.

Keywords: Click chemistry; Microwave; Huisgen cyclization; Heterogeneous catalysis; Ultrasound; Sonochemistry; Azides; Alkynes; Triazoles; Cyclodextrins.

References: 19 live references.