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Unified Azoline and Azole Syntheses by Optimized Aza‐Wittig Chemistry
Author(s) -
Loos Patrick,
Ronco Cyril,
Riedrich Matthias,
Arndt HansDieter
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201300160
Subject(s) - chemistry , wittig reaction , amide , intramolecular force , ring (chemistry) , tosyl , racemization , thioester , intramolecular reaction , tetrazole , ylide , enantiopure drug , stereochemistry , combinatorial chemistry , organic chemistry , enantioselective synthesis , catalysis , enzyme
Intramolecular aza‐Wittig ring closures were applied to synthesize thiazolines, oxazolines, and imidazolines from β‐azido thioester, ester, and amide precursors. The cyclization precursors were obtained from amino acid derivatives. Optimized conditions for diazo transfer with a fast rate and racemization suppression, (thio)esterification, and amide coupling reactions are described. The ring closure reaction can be executed with PPh 3 under neutral conditions and was found to be highly chemoselective for five‐membered rings. If amide groups were activated with tosyl groups, smooth intramolecular ring closure of iminophosphoranes furnished enantiopure imidazoline products with position‐specific tosyl protection. This aza‐Wittig‐based azoline synthesis was then extended to double azoline ring closures to furnish catenated azoline building blocks common to peptide natural product building blocks and their analogues.