DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM

  • Balázs Komjáti Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O. Box 91, Hungary; Servier Research Institute of Medicinal Chemistry, H-1031 Budapest, Záhony utca 7, Hungary
  • Bianka Szokol Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O. Box 91, Hungary
  • Benjámin Kováts Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O. Box 91, Hungary
  • Péter Kegye Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O. Box 91, Hungary
  • József Nagy Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, H-1521 Budapest, P.O. Box 91, Hungary

Abstract

The formal [2+2] cycloaddition of ketenes and imines, also known as Staudinger synthesis, is a facile method for the synthesis of biologically important β-lactam derivatives. In this paper two previously reported stereoselective reactions were investigated with computational methods. Our computations support experimental data that a chiral imine, derived from d-glyceraldehyde reacting with ketenes, yields almost exclusively one out of the possible four diastereomers. The reaction proceeds stepwise, first addition of the imine to the ketene yields an intermediate, then the product is formed in a conrotatory electrocyclization. Results indicate that the electrostatic repulsion of the chiral auxiliary group is the main factor of the stereoselectivity, but solvent and substituent effects are not negligible. Calculations were performed at M06-2X/6-31+G** level of theory combined with IEF-PCM solvation, in common solvents such as toluene, THF, dichloromethane, acetonitrile and water. These results provide useful insight for the development of new chiral auxiliaries and optimizing reaction parameters.

Keywords: β-lactam, ketene, imine, cycloaddition, DFT, PCM
Published online
2018-11-20
How to Cite
Komjáti, B., Szokol, B., Kováts, B., Kegye, P. and Nagy, J. (2018) “DFT Study of Stereoselective Ketene-imine Cycloadditions, Evaluation of Possible Solvent Effects with IEF-PCM”, Periodica Polytechnica Chemical Engineering, 62(4), pp. 503–509. doi: https://doi.org/10.3311/PPch.12527.
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Articles