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COMU: A Safer and More Effective Replacement for Benzotriazole‐Based Uronium Coupling Reagents
Author(s) -
ElFaham Ayman,
Funosas Ramon Subirós,
Prohens Rafel,
Albericio Fernando
Publication year - 2009
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200900615
Subject(s) - benzotriazole , reagent , chemistry , acceptor , combinatorial chemistry , organic chemistry , physics , condensed matter physics
We describe a new family of uronium‐type coupling reagents that differ in their iminium moieties and leaving groups. The presence of the morpholino group in conjunction with an oxime derivative—especially ethyl 2‐cyano‐2‐(hydroxyimino)acetate (Oxyma)—had a marked influence on the solubilities, stabilities, and reactivities of the reagents. Finally, the new uronium salt derived from Oxyma (COMU) performed extremely well in the presence of only 1 equiv of base, thereby confirming the effect of the hydrogen bond acceptor in the reaction. COMU also showed a less hazardous safety profile than the benzotriazole‐based HDMA and HDMB, which exhibited unpredictable autocatalytic decompositions. Furthermore, the Oxyma moiety contained in COMU suggests a lower risk of explosion than in the case of the benzotriazole derivatives.