Asymmetric 1,3-dipolar reactions of 3-sulfinylfuran- 2(5H)-ones with 11H-dibenzo[b,e]azepine 5-oxide. Synthesis of pyrroloazepines via isoxazoloazepines q Jos  e L. Garc  ıa Ruano, a, * J. Ignacio Andr  es Gil, b Alberto Fraile, a Ana Mar  ıa Mart  ın Castro a and M. Rosario Mart  ın a, * a Departamento de Qu  ımica Org anica, Universidad Aut onoma, Cantoblanco, 28049 Madrid, Spain b Johnson & Johnson Pharmaceutical Research & Development, Division of Janssen-Cilag, Medicinal Chemistry Department, Jarama St. s/n, 45007 Toledo, Spain Received 1 April 2004; revised 15 April 2004; accepted 20 April 2004 This paper is dedicated to Professor Jos e Luis Soto Abstract—The addition of morphanthridine N-oxide (1) to homochiral 3-p-tolylsulfinylfuran-2(5H)-ones (2a and 2b) under mild conditions affords furoisoxazoloazepines (3a and 3b) in high yields and with complete regioselectivity. The p-facial and endo- selectivities are also complete from 2a, which yields anti-3a-endo as the only diastereoisomer, whereas cycloreversion determines that the anti-3b-endo adduct can be almost exclusively isolated from 2b. Proper manipulation of the furoisoxazoloazepines allows the synthesis of the optically pure isoxazoloazepines and pyrroloazepines. Ó 2004 Elsevier Ltd. All rights reserved. The biological activity of molecules containing a modi- fied azepine ring has been intensively tested, both in vitro and in vivo, against various diseases. 1 In this context, 2-(aminoalkyl)-2,3,3a,8-tetrahydrodibenzo[c,f]- isoxazolo[2,3-a]azepines have been recently reported as 5-HT 2A=2C receptor antagonists, 2 and pyrroloazepines have displayed interesting biological activities, 3 which confers relevance to the search of short and highly stereoselective methods to prepare them. 1,3-Dipolar cycloadditions involving the use of nitrones as dipoles is one of the best reported methods to build the isoxa- zolidine skeleton. 4 It was used to prepare 2-(aminoalkyl)- 2,3,3a,8-tetrahydrodibenzo[c,f]isoxazolo[2,3-a]azepines starting from 11H-dibenzo[b,e]azepine 5-oxide (1). 2a Therefore we envisaged that the use of a proper enan- tiomerically pure dipolarophile would allow the asym- metric synthesis of the isoxazoloazepines, which in turn could be used to prepare pyrroloazepines. In our continuing interest in developing strategies to afford homochiral organic compounds using sulfoxides as chiral auxiliaries, 5 we have reported the efficiency of 3-p-tolylsulfinyl-5-alkoxyfuran-2(5H)-ones (2a and 2b 6 ) as chiral dipolarophiles in reactions with diazoalkanes, 7 nitrile oxides 8 and azomethine ylides. 9 In all these reactions, the sulfinyl group has shown its ability to improve the dipolarophilic features of the substrates. It prompted us to study the behaviour of furanones 2a and 2b with nitrone 1 to obtain the optically pure furo- isoxazoloazepines 3, which have the proper substituents to be transformed into highly functionalized iso- xazoloazepines and pyrroloazepines (Scheme 1). The synthetic results obtained in this study are reported in this paper. Results obtained in reactions of nitrones with vinyl sulfoxides 10 and 5-menthyloxyfuran-2(5H)-one 11 have been reported previously. However, none of these studies dealt with reactions of the nitrone 1, which has Keywords: 1,3-Dipolar reaction; Sulfoxides; Dibenzoazepines; Pyr- roloazepines. q Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.tetlet.2004.04.108 * Corresponding authors. Tel.: +34-3991-497-4703; fax: +3491-497- 3966; e-mail addresses: joseluis.garcia.ruano@uam.es; rosario. martin@uam.es 0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2004.04.108 Tetrahedron Letters 45 (2004) 4653–4656 Tetrahedron Letters