The dipolar route to azepin-3-one derivatives by heterocyclization of linear and monocyclic enallenyl nitrones as the key step

The recently discovered transformation of benzopentenynyl nitrones into 1,2-dihydrobenz[c]azepin-3-ones has been extended to the synthesis of structurally different systems including the monocyclic derivatives 17 and 18, the bicyclic azepinones 10a–d, and the tricyclic heterocycles 37–40, 42, 43, 45, 47, and 48. In addition, the applicability of the reaction principle was demonstrated through the preparation of the benzo-piperidino compound 52 which acts as a model compound for the alkaloid astrocasine (53). A multistep reaction mechanism is proposed that involves enallenyl nitrones as precursors of a 1,7-dipolar electrocyclization process followed by further bond reorganizations. The occurrence of cyclopropanones (type E and H) as intermediates is supported by the formation of isoindoles (41, 44, and 46) as minor products in some cases. Photochemical studies with selected dihydroazepinones gave different results: Whereas the monocyclic azepinone 17 reacted under both direct and sensitized excitation to form the bicyclic diastereomers 20 and 21, the reactions of the bicyclic compounds 10 were more complicated. Only 10a,b were observed to undergo the 4π-cyclization reaction upon direct irradiation, resulting, after CO extrusion and hydrolysis, in the formation of the aldehydes 22a,b. Under triplet-sensitized conditions 10b–d undergo a 1,5-phenyl shift to afford the isomers 25b–d. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)