[2,3]-Sigmatropic Rearrangements of 3-Sulfinyl Dihydropyrans: Application to the Syntheses of the Cores of ent-Dysiherbaine and Deoxymalayamicin A Roberto Ferna ´ndez de la Pradilla,* Nadia Lwoff, Miguel A ´ ngel del A ´ guila, Mariola Tortosa, and Alma Viso Instituto de Quı ´mica Orga ´nica, CSIC, Juan de la CierVa, 3, 28006 Madrid, Spain iqofp19@iqog.csic.es ReceiVed July 23, 2008 The [2,3]-sigmatropic rearrangement of a variety of configurationally stable diastereomeric allylic sulfinyl dihydropyrans, produced by base-promoted cyclization of sulfinyl dienols, has been studied. In some cases, the efficient transformation of these substrates into dihydropyranols required an in-depth study of reaction conditions, with the preferred protocol relying on the use of DABCO in warm toluene. This methodology has been applied to the syntheses of the cores of ent-dysiherbaine and deoxymalayamicin A by means of efficient tethered aminohydroxylations. Introduction The[2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenates originally developed by Mislow, 1 Braverman, 2 and Evans 3 is a reversible process that can cause the racem- ization of allylic sulfoxides I, via the intermediate sulfenate esters II, that can transform into enantiomeric sulfoxides III (Scheme 1). 4 The presence of a suitable thiophile can cleave the O-S bond in the sulfenate intermediate, rendering the process irreversible by removing the sulfur atom and leading to an allylic alcohol IV. Allylic alcohols are important sub- structures in many bioactive products and also key building blocks in organic synthesis since they can be involved in a variety of stereocontrolled chemical transformations that allow for the creation of new functionalities. 5 The conversion of sulfoxides into allylic alcohols has been widely used with synthetic purposes since it may benefit from the chiral auxiliary properties of sulfoxides, and represents an easy procedure for removal of the sulfur moiety which usually is not present in final synthetic targets. 6 During the past few years our group has developed the stereocontrolled cyclization of hydroxy sulfinyl dienes with different bases depending on the diene geometry to obtain configurationally stable sulfinyl dihydropyrans 3-6 with 2,3- trans and 2,3-cis relative configuration (Scheme 2). 7 These substrates present a peculiar arrangement of functionalities that suggests that different reactivities should be considered, for instance, under basic reaction conditions; these include oxygen -elimination and cleavage of the dihydropyran ring, epimer- ization R to the sulfoxide, and for 2,3-trans substrates the possible pyrolitic syn-elimination of the sulfoxide moiety. * To whom correspondence should be addressed. Fax: 34-91-564-4853. (1) (a) Rayner, D. R.; Miller, E. G.; Bickart, P.; Gordon, A. J.; Mislow, K. J. Am. Chem. Soc. 1966, 88, 3138–3139. (b) Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869–4876. (2) Braverman, S.; Stabinsky, Y. J. Chem. Soc., Chem. Commun. 1967, 270– 271. (3) Evans, D. A.; Andrews, G. C.; Sims, C. L. J. Am. Chem. Soc. 1971, 93, 4956–4957. (4) (a) Braverman, S. In The Chemistry of Sulphones and Sulphoxides; Patai, S., Rappoport, Z., Stirling, C. J. M., Eds.; John Wiley & Sons: New York, 1988; p 717. (b) Evans, D. A.; Andrews, G. C. Acc. Chem. Res. 1974, 7, 147–155. (c) Reggelin, M. Top. Curr. Chem. 2007, 275, 1–65. (5) (a) Chen, Q.; Qing, F.-L. Tetrahedron 2007, 63, 11965–11972. (b) Griesbeck, A. G.; El-Idreesy, T. T.; Lex, J. Tetrahedron 2006, 62, 10615–10622. (c) Fournier, J. F.; Mathieu, S.; Charette, A. B. J. Am. Chem. Soc. 2005, 127, 13140–13141. (d) Adam, W.; Bottke, N. J. Am. Chem. Soc. 2000, 122, 9846– 9847. (e) Adam, W.; Wirth, T. Acc. Chem. Res. 1999, 32, 703–710. (6) Recent examples: (a) Ferna ´ndez de la Pradilla, R.; Lwoff, N. Tetrahedron Lett. 2008, 49, 4167–4169. (b) Ferna ´ndez de la Pradilla, R.; Lwoff, N.; Viso, A. Tetrahedron Lett. 2007, 48, 8141–8144. (c) Brebion, F.; Na `jera, F.; Delouvrié, B.; Laco ˆte, E.; Fensterbank, L.; Malacria, M. Synthesis 2007, 2273–2278. (d) Pelc, M. J.; Zakarian, A. Tetrahedron Lett. 2006, 47, 7519–7523. (e) Koprowski, M.; Krawczyk, E.; Skowron ˜ska, A.; McPartlin, M.; Choi, N.; Radojevic, S. Tetrahedron 2001, 57, 1105–1118. For an example retaining the sulfur atom see: (f) Satoh, T.; Miyagawa, T. Tetrahedron Lett. 2006, 47, 1981–1983. (7) (a) Ferna ´ndez de la Pradilla, R.; Tortosa, M. Org. Lett. 2004, 6, 2157– 2160. (b) Ferna ´ndez de la Pradilla, R.; Tortosa, M.; Lwoff, N.; del A ´ guila, M. A.; Viso, A. J. Org. Chem. 2008, 73, 6716–6727. 10.1021/jo8015709 CCC: $40.75  2008 American Chemical Society J. Org. Chem. 2008, 73, 8929–8941 8929 Published on Web 10/22/2008