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A Scalable Metal‐, Azide‐, and Halogen‐Free Method for the Preparation of Triazoles
Author(s) -
Clark Peter R.,
Williams Glynn D.,
Hayes Jerome F.,
Tomkinson Nicholas C. O.
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201915944
Subject(s) - azide , chemistry , amine gas treating , cycloaddition , combinatorial chemistry , halogen , alkyne , yield (engineering) , coupling reaction , organic chemistry , catalysis , materials science , alkyl , metallurgy
A scalable metal‐, azide‐, and halogen‐free method for the synthesis of substituted 1,2,3‐triazoles has been developed. The reaction proceeds through a 3‐component coupling of α‐ketoacetals, tosyl hydrazide, and a primary amine. The reaction shows outstanding functional‐group tolerance with respect to both the α‐ketoacetal and amine coupling partners, providing access to 4‐, 1,4‐, 1,5‐, and 1,4,5‐substituted triazoles in excellent yield. This robust method results in densely functionalised 1,2,3‐triazoles that remain challenging to prepare by azide–alkyne cycloaddition (AAC, CuAAC, RuAAC) methods and can be scaled in either batch or flow reactors. Methods for the chemoselective reaction of either aliphatic amines or anilines are also described, revealing some of the potential of this novel and highly versatile transformation.