A Scalable Metal‐, Azide‐, and Halogen‐Free Method for the Preparation of Triazoles. Issue 17 (10th March 2020)

• Record Type: Journal Article
• Authors: Clark, Peter R.; Williams, Glynn D.; Hayes, Jerome F.; Tomkinson, Nicholas C. O.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 17(2020)
• Page Start: 6740
• Page End: 6744
• Publication Date: 2020-03-10
• Subjects: α-ketoacetals -- amines -- heterocycles -- synthetic methods -- triazoles; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201915944
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: 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. Abstract : Three for three : A simple and efficient redox‐neutral three‐component synthesis of 1, 2, 3‐triazoles from α‐ketoacetals, N ‐tosylhydrazide, and a primary amine is reported. This method provides access to all triazole substitution patterns, without the requirement for azides, alkynes, halides, transition metals, or oxidants.