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

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• ,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: acid amide; diethyl mesoxalate; N

• esters and N-acyl groups is limited to acetyl, benzoyl, and alkoxycarbonyl groups [15]. Conversely, NAIs derived from α-oxomalonic acid diester are more versatile. Nagao et al. prepared NAI 2 through the aza-Wittig reaction of diethyl mesoxalate (DEMO, diethyl α-oxomalonate). However, only the N-acetyl

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• diesters and ester amides as key intermediates (+)-Awajanomycin Diethyl mesoxalate (90a) is a valuable building block due to the high density of carbon atoms in high oxidation states. As a vic-tricarbonyl compound, its central keto group is an especially potent electrophile. The Koert group used this

• reactivity in their synthesis of (+)-awajanomycin (92), a marine natural product with a γ-lactone-δ-lactam core structure (Scheme 15) [30][31]. Key step was an asymmetric allylboration of diethyl mesoxalate (90a) with boronate 89, which was easily accessible through a Matteson homologation of dichloromethyl