Unusual Enantiopure Heterocyclic Skeletons by Lewis Acid Promoted Rearrangements of 1,3-Dioxolanyl-Substituted 1,2-Oxazines

Abstract

Lewis acid promoted rearrangements of different 4-alkoxy-substituted 1,2-oxazines syn-1 are reported. Depending on the nature of this alkoxy group different reaction pathways are possible either providing bicyclic 1,2-oxazinones 2 or the novel tricyclic products 3–5. A mechanistic rational describing the role of the 4-alkoxy group is presented. The key step for formation of tricyclic skeletons 3–5 is a 1,2-alkyl shift. Hydrogenation reactions of these tricyclic compounds gave unsaturated 1,2-oxazines 12 and 13 or tetrahydrofurans 15a–c/16a–c depending on the time of hydrogenolysis. Tetrahydrofuryl-annulated 1,2-oxazine 12 was used for further transformations into complex substituted tetrahydrofurans. Reduction with sodium cyanoborohydride and subsequent cleavage of the N,O-bond by hydrogenation furnished aminofuran derivative 19. Alternatively treatment with a strong base such as n-butyllithium afforded imidoester 21 via a Beckmann-type fragmentation.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)