Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

Abstract

A copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ, making this protocol operationally simple. The Cu(I) catalyst not only participates in the alkyl diacyl peroxides decomposition to afford alkyl azides but also catalyzes the subsequent CuAAC reaction to produce the 1,2,3-triazoles.

Keywords: 1,2,3-triazoles; alkyl diacyl peroxides; azidotrimethylsilane; click reaction; copper catalysis; radical.

Scheme 1

General methods for the synthesis of triazoles.

Scheme 2

Substrate scope of the terminal alkynes. Conditions: 1 (0.5 mmol), 2a (0.75 mmol), TMSN₃ (0.75 mmol), CuCl (10 mol %), DCM (2 mL), 50 °C, 10 h. Yields of the isolated products are given.

Scheme 3

Substrate scope of the alkyl diacyl peroxides. Conditions: 1a (0.5 mmol), 2 (0.75 mmol), TMSN₃ (0.75 mmol), CuCl (10 mol %), DCM (2 mL), 50 °C, 10 h. Yields of the isolated products are given.

Scheme 4

Preliminary mechanistic studies.

Scheme 5

Plausible reaction mechanism.