New highly strained multifunctional heterocycles by intramolecular cycloadditions of nitrones to bicyclopropylidene moieties

Abstract

Intramolecular cycloadditions of various nitrone functionalities with different substituents (R = Me, Bn, tBu) at the nitrogen atom tethered to a bicyclopropylidene unit through a two-carbon chain led to cis-fused tricyclic isoxazolidines (3-alkyl-3,3a,4,5,5a,6-hexahydrocyclopropa[2,3]cyclopenta[1,2-c]isoxazolespiro[1,1']cyclopropanes) 26 in 42-58% yield with complete regio- and diastereoselectivity. The thermal rearrangement of the cycloadducts 26 under neutral conditions afforded the corresponding tricyclic tetrahydropyridones 27 (52-53%). The analogous starting materials with a three-carbon tether, the 4-(bicyclopropyliden-2-yl)butylidenenitrones furnished tricyclic isoxazolidines 28 (54-58%) and tetrahydropyridones 29 (55-64%) by subsequent thermal rearrangement. Under acidic conditions (TFA), the cycloadducts 26 and 28 underwent fragmentative rearrangements to afford the tricyclic beta-lactams 30 and 32 (50-66%), respectively, of which the former suffered amide-bond cleavage in situ to provide the corresponding N-trifluoroacetyl beta-amino acid derivatives 31 (68-71%). ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).