Highly Regioselective Synthesis of 3,5-Substituted Pyrazoles from Bromovinyl Acetals and N-Tosylhydrazones
Anne Westermeyer, Quentin Llopis, Gérard Guillamot, Phannarath Phansavath*, Virginie Ratovelomanana-Vidal*
*Institute of Chemistry for
Life and Health Sciences, 11 rue Pierre et Marie Curie, 75005 Paris,
France, Email: phannarath.phansavath
chimie-paristech.fr, virginie.vidalchimie-paristech.fr
A. Westermeyer, Q. Llopis, G. Guillamot, P. Phansavath, V. Ratovelomanana-Vidal, Synlett, 2020, 31, 1172-1176.
DOI: 10.1055/s-0039-1690885
see article for more reactions
Abstract
A regioselective 1,3-dipolar cycloaddition of diazo compounds, generated in situ from N-tosylhydrazones, with unactivated bromovinyl acetals, which serve as alkyne surrogates, provides 3,5-disubstituted pyrazoles in good yields. The reaction tolerates N-tosylhydrazones bearing various substituted benzylidene groups, and a range of 3,5-disubstituted pyrazoles.
see article for more examples
Details
The document details a highly regioselective synthesis of 3,5-disubstituted pyrazoles via 1,3-dipolar cycloaddition of diazo compounds, generated in situ from N-tosylhydrazones, with unactivated bromovinyl acetals. This method, developed by researchers from PSL University and SEQENS, offers a new approach to synthesizing pyrazoles, which are significant in pharmaceuticals and agribusiness. The reaction tolerates various substituted benzylidene groups, yielding pyrazoles in 43-92% yields. Optimization showed that K2CO3 in refluxing THF provided the best results. The scope includes electron-donating and electron-withdrawing groups, halogenated N-tosylhydrazones, and pyridine-substituted N-tosylhydrazones, demonstrating broad applicability. The reaction's regioselectivity was confirmed by X-ray crystallography. This method is scalable, as demonstrated by multi-gram experiments yielding higher than small-scale reactions. The study was funded by SEQENS, the French Ministry of Higher Education, Research and Innovation, and the CNRS. The findings provide a practical, functional-group-tolerant, and operationally simple transformation for synthesizing pyrazoles, expanding the toolkit for creating acetal-containing molecular scaffolds.
Key Words
pyrazoles, 1,3-dipolar cycloaddition, bromovinyl acetals, tosylhydrazones
ID: J72-Y2020
