N-силілімін трифторопірувату в асиметричному синтезі похідних трифтороаланіну

• Дата: 2023
• Автори: Cherednichenko, Alona S., Rassukana, Yuliya V.
• Формат: Стаття
• Мова: English
• Опубліковано: National University of Pharmacy 2023
• Теми: асиметричний синтез; N-силілімін; реакція Манніха; α-аміно-γ-оксокарбоксилат; трифторометил; asymmetric synthesis; N-silylimine; Mannich reaction; trifluoromethyl; α-amino-γ-oxocarboxylate
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/284819
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

Aim. To develop a preparative method for the synthesis of N-trimethylsilylimine of trifluoropyruvate, and study its interaction with acetone under organocatalytic conditions.Results and discussion. A simple preparative approach to the first representative of N-silylimines of trifluoropyruvate was developed based on the interaction of triphenylphosphinimide and trifluoropyruvic acid methyl ester by the aza-Wittig reaction. It was found that the addition of acetone to N-silylimine occurred in the presence of L- or D-proline and led to the formation of enantiomerically enriched α-amino-γ-oxocarboxylates. The hydrolysis of the ester function resulted in (R)-α-trifluoromethyl aminocarboxylic acid, and the cyclocondensation with isocyanates or 2,5-dimethoxytetrahydrofuran yielded nitrogen-containing heterocycles containing pyrimidine or pyrrolizine nuclei.Experimental part. The synthetic procedures for the N-silylimine of trifluoropyruvate and its reaction with acetone are provided, along with the transformations of obtained α-amino-γ-oxocarboxylates (hydrolysis, cyclocondensations with isocyanates and 2,5-dimethoxytetrahydrofuran). The structures of the compounds synthesized were proven by 1H, 13C, 19F NMR spectroscopy methods, as well as by the elemental analysis.Conclusions. A convenient method for the synthesis of N-silylimine of trifluoropyruvate has been developed. Using the example of the Mannich reaction with acetone, it has been demonstrated that N-silylimine of trifluoropyruvate is a convenient substrate for the synthesis of optically active 3,3,3-trifluoroalanine derivatives.