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16 O/ 18 O Exchange of Aldehydes and Ketones caused by H 2 18 O in the Mechanistic Investigation of Organocatalyzed Michael, Mannich, and Aldol Reactions
Author(s) -
Hayashi Yujiro,
Mukaiyama Takasuke,
Benohoud Meryem,
Gupta Nishant R.,
Ono Tsuyoshi,
Toda Shunsuke
Publication year - 2016
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.201600280
Subject(s) - aldol reaction , nucleophile , chemistry , mannich reaction , aldehyde , ketone , enamine , catalysis , reaction mechanism , amine gas treating , enol , organocatalysis , organic chemistry , michael reaction , medicinal chemistry , enantioselective synthesis
Organocatalyzed Michael, Mannich, and aldol reactions of aldehydes or ketones, as nucleophiles, have triggered several discussions regarding their reaction mechanism. H 2 18 O has been utilized to determine if the reaction proceeds through an enamine or enol mechanism by monitoring the ratio of 18 O incorporated into the final product. In this communication, we describe the risk of H 2 18 O as an evaluation tool for this mechanistic investigation. We have demonstrated that exchange of 16 O/ 18 O occurs in the aldehyde or ketone starting material, caused by the presence of H 2 18 O and amine catalysts, before the Michael, Mannich, and aldol reactions proceed. Because the newly generated 18 O starting aldehydes or ketones and 16 O water affect the incorporation ratio of 18 O in the final product, the use of H 2 18 O would not be appropriate to distinguish the mechanism of these organocatalyzed reactions.