16O/18O Exchange of Aldehydes and Ketones caused by H218O in the Mechanistic Investigation of Organocatalyzed Michael, Mannich, and Aldol Reactions. Issue 17 (10th March 2016)

• Record Type: Journal Article
• Authors: Hayashi, Yujiro; Mukaiyama, Takasuke; Benohoud, Meryem; Gupta, Nishant R.; Ono, Tsuyoshi; Toda, Shunsuke
• Is Part Of: Chemistry. Volume 22:Issue 17(2016)
• Page Start: 5868
• Page End: 5872
• Publication Date: 2016-03-10
• Subjects: asymmetric synthesis -- enamines -- enols -- organocatalyst -- reaction mechanisms; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201600280
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Organocatalyzed Michael, Mannich, and aldol reactions of aldehydes or ketones, as nucleophiles, have triggered several discussions regarding their reaction mechanism. H2 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 H2 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 H2 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 H2 18 O would not be appropriate to distinguish the mechanism of these organocatalyzed reactions. Abstract : Exchange of 16 O/ 18 O occurs in the aldehyde or ketone starting material in the presence of H2 18 O and amine catalysts before the organocatalyzed Michael, Mannich, and aldol reactions proceed. Because the newly generated 18 O starting aldehyde or ketone and 16 O water affect the incorporation ratio of 18 O in the final product, the use of H2 18 O would not be appropriate for distinguishing between the enamine and enol pathway for these types of transformation (see scheme).