Functionalization of 1,3,4-Oxadiazoles and 1,2,4-Triazoles via Selective Zincation or Magnesiation Using 2,2,6,6-Tetramethylpiperidyl Bases

Kuno Schwärzer; Carl Phillip Tüllmann; Simon Graßl; Bartosz Górski; Cara E Brocklehurst; Paul Knochel

doi:10.1021/acs.orglett.0c00238

Functionalization of 1,3,4-Oxadiazoles and 1,2,4-Triazoles via Selective Zincation or Magnesiation Using 2,2,6,6-Tetramethylpiperidyl Bases

Org Lett. 2020 Mar 6;22(5):1899-1902. doi: 10.1021/acs.orglett.0c00238. Epub 2020 Feb 12.

Authors

Kuno Schwärzer¹, Carl Phillip Tüllmann¹, Simon Graßl¹, Bartosz Górski², Cara E Brocklehurst³, Paul Knochel¹

Affiliations

¹ Department Chemie, Ludwig-Maximilians-Universität München, Butenandtstraße 5-13, Haus F, 81377 München, Germany.
² Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
³ Global Discovery Chemistry, Novartis Institutes for BioMedical Research, 141 Klybeckstrasse, 4057 Basel, Switzerland.

PMID: 32048510
DOI: 10.1021/acs.orglett.0c00238

Abstract

We report the metalation of the 1,3,4-oxadiazole and 1,2,4-triazole scaffolds via regioselective zincation or magnesiation using the TMP bases (TMP = 2,2,6,6-tetramethylpiperidyl) TMP₂Zn·2LiCl, TMP₂Zn·2MgCl₂·2LiCl, TMPMgCl·LiCl, and TMPZnCl·LiCl under mild conditions in THF. Subsequent trapping with various electrophiles including hydroxylamino benzoates gives access to functionalized heterocycles while tolerating many functional groups.

Publication types

Research Support, Non-U.S. Gov't