Stereoselective synthesis of 4-hydroxymethyl-1,3-oxazolidin-2-one derivatives from novel 2-hydroxymethylaziridines

Abstract

A stereoselective and simple method for the synthesis of trans-2-hydroxymethyl-N-alkyl-1,3-oxazolidin-2-ones is described. The synthesis involved the reduction of trans-aziridine-2-carboxylates with LiAlH₄, followed by a ring opening and a cyclization reaction in the presence of methyl chloroformate to afford the target trans-oxazolidinones in completely regio- and stereoselective process. A plausible reaction mechanism has been proposed involving an S_N1 pathway and a detailed computational study of this mechanistic process has been carried out using theoretical calculations.

Graphical Abstract

Keywords:

• Computational study; ethyl trans-N-alkylaziridine-2-carboxylates
• trans-2-hydroxymethyl-N-alkylaziridines
• trans-2-hydroxymethyl-N-alkyl-1,3-oxazolidin-2-ones
• ring-expansion reaction

Supplementary information

Supplemental data of this paper includes full experimental detail and a copy of ¹H, ¹³C NMR. This material can be found via the “Supplementary content” section of the article's webpage.

Additional information

Funding

The authors are grateful to the Tunisian Ministry of Higher Education and Scientific Research for financial support of this research [LR99ES15].