An unusual thermodynamic preference of chiral N-arylsulfonyl cis-3-alkyl-2-vinylaziridines over their trans-isomers: palladium(0)-catalysed equilibration reactions

Abstract

Palladium (0)-catalysed reactions of N-alkylsulfonyl-or N-arylsulfonyl-3-alkyl-2-vinylaziridines reveal that 2,3-cisisomers are more stable than the corresponding 2,3-truns-isomers in accord with ab initio calculations.Activated chiral aziridines, notably 2-~inylaziridines~ and their derivatives,3 are versatile synthetic intermediates for the synthesis of biologically important compounds. Recently we,4 Mercks and Dupont Merck6 groups, and Panek7 have reported that peptides containing (E)-alkene dipeptide isosteres show potent biological activity. As part of an ongoing project aimed at the synthesis of biologically active peptides containing (E)alkene isosteres* we required a reliable method for the preparation of activated cis-3-alkyl-2-vinylaziridines 4, key synthetic intermediates in the synthesis of these isosteres.Chiral activated 3-alkyl-2-vinylaziridines 4 and 5 could be derived from a homochiral N-protected amino aldehyde 1 via amino alcohols 2 and 3. However, the highly stereoselective synthesis of either syn-or anti-amino alcohols 2 or 3 and hence 2,3-cisor 2,3-trans-3-alkyl-2-vinylaziridines 4 or 5 from an amino aldehyde 1 has hitherto been difficult.

Additions of stabilised and semi-stabilised sulfur ylides to tosyl protected imines: are they under kinetic or thermodynamic control?

“…Indeed, it has been shown experimentally that cis aziridines are thermodynamically more stable then the corresponding trans isomers: palladium-catalysed isomerisation of unsaturated aziridines 18 and base-catalysed isomerisation of aziridinyl Scheme 14 Cross-over experiments with amide-stabilised sulfur ylide precursors.…”

A Thermodynamic Preference of Chiral N-Methanesulfonyl and N-Arenesulfonyl 2,3-cis-3-Alkyl-2-Vinylaziridines over Their 2,3-Trans-Isomers: Useful Palladium(0)-Catalyzed Equilibration Reactions for the Synthesis of (E)-Alkene Dipeptide Isosteres

“…It was expected that palladium(0)-catalyzed isomerization of 2,3- trans -3-alkyl-2-vinylaziridines 3 into the corresponding desired cis -isomers 4 could occur via π-allyl palladium complexes. Here we detail a study involving the palladium(0)-catalyzed equilibrated reaction of chiral N -(methanesulfonyl)- and N -(arenesulfonyl)-3-alkyl-2-vinylaziridines and N -(arenesulfonyl)-4-alkyl-5-vinyloxazolidin-2-ones …”

Scope and limitations in sulfur ylide mediated catalytic asymmetric aziridination of imines: use of phenyldiazomethane, diazoesters and diazoacetamides†

“…Thus cisaziridines must be thermodynamically more stable than the corresponding trans isomers. Indeed, this has been verified experimentally as palladium catalysed isomerisation of unsaturated aziridines 36 and base catalysed isomerisation of aziridinyl ketones 37 give cis-aziridines predominantly. The thermodynamic preference for the cis-aziridine can be understood in terms of steric hindrance.…”