Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

Kento Iwai; Akari Hikasa; Kotaro Yoshioka; Shinki Tani; Kazuto Umezu; Nagatoshi Nishiwaki

doi:10.3762/bjoc.20.238

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

Beilstein J Org Chem. 2024 Nov 6:20:2827-2833. doi: 10.3762/bjoc.20.238. eCollection 2024.

Authors

Kento Iwai^{1

2

3}, Akari Hikasa¹, Kotaro Yoshioka⁴, Shinki Tani⁴, Kazuto Umezu⁴, Nagatoshi Nishiwaki^{1

2}

Affiliations

¹ School of Engineering Science, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan.
² Research Center for Molecular Design, Kochi University of Technology, Tosayamada, Kami, Kochi 782-8502, Japan.
³ Department of Chemistry, Faculty of Science, Nara Women's University, Kitauoyahigashimachi, Nara 630-8506, Japan.
⁴ Kumiai Chemical Industry Co. Ltd., Nakanogo, Fuji, Shizuoka 421-3306, Japan and 5K • I Chemical Industry Co. Ltd., Shinoshinden, Iwata, Shizuoka 437-1213, Japan.

Abstract

The N,O-acetal derived from diethyl mesoxalate (DEMO) undergoes elimination of acetic acid upon treatment with a base, leading to the formation of N-acylimine in situ. Lithium acetylide readily attacks the imino group to afford N,1,1-tricarbonylated propargylamines. When the resulting propargylamine reacts with butyllithium, ring closure occurs between the ethynyl and carbamoyl groups, yielding 2,5-disubstituted oxazole-4-carboxylates. This cyclization also occurs when the propargylamine is heated with ammonium acetate, resulting in double activation.

Keywords: N-acylamine; acid amide; diethyl mesoxalate; oxazole; propargylamine.