N1-Selective Methylation of Pyrazoles via α‑Halomethylsilanes as Masked Methylating Reagents

The development of a highly selective N-methylation of pyrazole heterocycles using commercially available, bench-stable α-halomethylsilanes as masked methylating reagents is described. Sterically bulky α-halomethylsilanes significantly improve the selectivity of N-alkylation over traditional methyla...

Full description

Saved in:
Bibliographic Details
Published inJournal of organic chemistry Vol. 89; no. 6; pp. 4221 - 4224
Main Authors Yang, Emma, Dalton, Derek M.
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 15.03.2024
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
REGIOSELECTIVE SYNTHESIS
Online AccessGet full text

Cover

More Information
Summary:The development of a highly selective N-methylation of pyrazole heterocycles using commercially available, bench-stable α-halomethylsilanes as masked methylating reagents is described. Sterically bulky α-halomethylsilanes significantly improve the selectivity of N-alkylation over traditional methylating reagents and readily undergo protodesilylation in the presence of a fluoride source and water to give N-methyl pyrazoles. Selectivities of 92:8 to >99:1 N1/N2 regioisomeric ratios were achieved with a range of pyrazole substrates in good yields.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.3c02841