Transition Metal-catalyzed Isomerization of Aziridines and Its Application to the Synthesis of Highly Active Isosteres

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Transition metal-catalyzed isomerization of aziridines and its application to the synthesis of highly active isosteres has been investigated.1.A thermodynamic relative stabilities between 2,3-cis-3-alkyl-2 vinyl-N-methanesulfonylaziridine and its 2,3-trans-isomers have been investigated by ab initio calculations. It became apparent that 2,3-cis-3-alkyl-2 vinyl-N-methanesulfonylaziridine is more stable than its 2,3-trans-isomer.2.2,3-cis-3-Alkyl-2-vinyl-N-methanesulfonylaziridine is more stable than its 2,3-trans-isomer by ca. 1.0kcal/mol.3.Chiral 2-vinylaziridines bearing an N-aklylsulfonyl or N-arylsulfonyl group were synthesized from either natural alpha-amino acids or chiral 2,3-epoxy alcohols.4.Palladium (0)-catalyzed reactions of 2,3-trans-N-methanesulfonyl-or 2,3-cis-N-(arenesulfonyl)-3-alkyl-2-vinylaziridines gave equilibrium mixtures. Palladium (0)-catalyzed reactions of 2,3-trans-N-methanesulfonylaziridines gave a 95 : 5 equilibrium mixture of 2,3-cis-and 2,3-trans-isomers.5.An efficient synthetic route to (E)-alkene dipeptide isosteres from 2,3-cis-3-alkyl-2-vinylaziridines have been developed.Bioactive peptides involving various (E)-alkene dipeptide isosteres have been synthesized.