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Fine‐Tunable Tris(triazolyl)methane Ligands for Copper(I)‐ Catalyzed Azide–Alkyne Cycloaddition Reactions
Author(s) -
Ozkal Erhan,
Llanes Patricia,
Bravo Fernando,
Ferrali Alessandro,
Pericàs Miquel A.
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201300887
Subject(s) - chemistry , cycloaddition , azide , alkyne , toluene , catalysis , click chemistry , tetrahydrofuran , combinatorial chemistry , solvent , photochemistry , organic chemistry
The preparation of a small library of modular tris(triazolyl)methane ligands for copper‐catalyzed azide–alkyne cycloaddition (CuAAC) reactions is reported. The synthesis of the first generation ligand, tris(1‐benzyl‐1 H ‐1,2,3‐triazol‐4‐yl)methanol ( 1a ), suitable for work in aqueous systems, is reported at the 50–100 mmol scale through a one‐stage, environmentally benign procedure. One‐stage procedures for the synthesis of tris(aryltriazolyl)methanol structures ( 1b , phenyl; 1c , para ‐trifluoromethylphenyl; 1d , para ‐methoxyphenyl) designed for electronic fine‐tuning of catalytic properties, and of 1a ‐derived ethers 2c (OBn) and 2d (OMe), designed for CuAAC reactions in organic solvents, are also reported. The complete set of ligands ( 1a–d , 2c–d ) has been tested in the reaction of phenylacetylene with benzyl azide in six different solvents (water, hexane, toluene, dichloromethane, tetrahydrofuran, and acetonitrile), and this has allowed the identification of 1b , 1c and 2c as the ligands depicting the highest tolerance to changes in solvent polarity within the considered family. The comparative performance of ligands 1b–d and 2c in the cycloaddition of a small family of alkynes with benzyl azide in two very different reaction media (1:1 t‐ BuOH/H 2 O and toluene) has been studied as a guide for catalyst selection in specific applications. The applicability of 1c in CuAAC reactions involving functional substrates in toluene has been explored under thermal and microwave‐accelerated (tandem azide formation plus CuAAC reaction) reaction conditions.