Synthesis of Bis(functionalized) Aminals via Successive Nucleophilic Amidation and Amination

The central carbonyl group of diethyl mesoxalate (DEMO) exhibits high electrophilicity that allows it to be attacked by versatile nucleophiles. Even a less nucleophilic acid amide serves as a nucleophile to produce N,O-acetal upon treatment with DEMO in the presence of acetic anhydride. When the obt...

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Bibliographic Details
Published in:Journal of organic chemistry 2023-02, Vol.88 (4), p.2207-2213
Main Authors: Iwai, Kento, Hikasa, Akari, Yoshioka, Kotaro, Tani, Shinki, Umezu, Kazuto, Nishiwaki, Nagatoshi
Format: Article
Language:English
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Summary:The central carbonyl group of diethyl mesoxalate (DEMO) exhibits high electrophilicity that allows it to be attacked by versatile nucleophiles. Even a less nucleophilic acid amide serves as a nucleophile to produce N,O-acetal upon treatment with DEMO in the presence of acetic anhydride. When the obtained N,O-acetal was treated with a base, the elimination of acetic acid generated N-acylimine in situ. N-Acylimine is also highly electrophilic, allowing it to accept the second nucleophilic addition by an amine, resulting in α,α-bis­(functionalized) aminals. This protocol facilitates the modification of the two different amino groups by altering nucleophiles, resulting in the production of tetra-functionalized methane derivatives on demand. The ring closure between the amide moiety and the amino group was achieved using the structural features to form a six-membered ring.
ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c02647