N-Silylimine of Trifluoropyruvate in the Asymmetric Synthesis of Trifluoroalanine Derivatives

Alona S. Cherednichenko; Yuliya V. Rassukana

doi:10.24959/ophcj.23.284819

Authors

Alona S. Cherednichenko Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0009-0001-7159-6898
Yuliya V. Rassukana Institute of Organic Chemistry of the National Academy of Sciences of Ukraine, Ukraine https://orcid.org/0000-0003-3101-9911

DOI:

https://doi.org/10.24959/ophcj.23.284819

Keywords:

asymmetric synthesis, N-silylimine, Mannich reaction, trifluoromethyl, α-amino-γ-oxocarboxylate

Abstract

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.

Supporting Agency

The author received no specific funding for this work.

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