General Method for Synthesizing Pyranoid Glycals. A New Route to Allal and Gulal Derivatives Omar Boutureira, Miguel Angel Rodrı ´guez, M. Isabel Matheu, Yolanda Dı ´az,* and Sergio Castillo ´ n* Departament de Quı ´mica Analı ´tica i Quı ´mica Orga ` nica, Facultat de Quı ´mica, UniVersitat RoVira i Virgili, C/Marcel.lı ´ Domingo s/n, 43007 Tarragona, Spain sergio.castillon@urV.net; yolanda.diaz@urV.net Received November 26, 2005 ABSTRACT Pyranoid glycals of all configurations can be obtained from pentoses through an olefination-cyclization-elimination sequence. The elimination can be carried out with excellent yields under radical conditions or by using common reductive reagents such as Zn/Cu, TiCl 4 /LiAlH 4 , or lithium naphthalenide. The proposed method is appropriate for the synthesis of glycals with allo or gulo configurations because the cyclization step is more efficient for these substrates. Access to glycals is important in the glycosylation field for the synthesis of oligosaccharide motifs, 1 C-glycosides, 2 C-nucleosides, 3 nucleosides, 4 and other biologically important molecules. 5-7 The growing appreciation that glycoconjugates play an important role in cell recognition processes has spurred the synthesis of many glycoconjugates via the glycal method. In some cases, this effort has been conducted with the aim of developing synthetic vaccines. If new structural motifs are to be built up, it will be necessary to provide a variety of glycals of different configurations. In this respect, the only pyranoid glycals that are readily accessible currently are either D-glucal and D-galactal or L-rhamnal. Other D-glycals (such as D-gulal and D-allal, etc.) are not readily available. 8 The Fischer-Zach method for forming glycals, which uses zinc dust in acetic acid in the reductive elimination of acylated glycosyl bromides, has been one of the most popular methods for synthesizing glycals (Scheme 1). 9 Over the years, this procedure has undergone countless modifications regard- ing the anomeric leaving group (Cl, SPh, S(O)Ph, SO 2 Ph, (1) (a) Danishefsky, S. J.; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl. 1996, 35, 1380-1419. (b) Roberge, J. Y.; Beebe, X.; Danishefsky, S. J. J. Am. Chem. Soc. 1998, 120, 3915-3927. (c) McDonald, F. E.; Zhu, H. Y. H. J. Am. Chem. Soc. 1998, 120, 4246-4247. (d) Thiem, J.; Gerken, M. J. Org. Chem. 1985, 50, 954-958. (2) (a) Thorn, S. N.; Gallagher, T. Synlett 1996, 856. (b) Hosokawa, S.; Kirschbaum, B.; Isobe, M. Tetrahedron Lett. 1998, 39, 1917-1920. (3) (a) Erion, M. D.; Rydzewski, R. M. Nucleosides Nucleotides 1997, 16, 315-337. (b) Walker, J. A., II; Chen, J. J.; Hinkley, J. M.; Wise, D. S.; Townsend, L. B. Nucleosides Nucleotides 1997, 16, 1999-2012. (4) (a) Robles, R.; Rodrı ´guez, C.; Izquierdo, I.; Plaza, M. T.; Mota, A. Tetrahedron: Asymmetry 1997, 8, 2959-2965. (b) Dı ´az, Y.; El-Laghdach, A.; Castillo ´n, S. Tetrahedron 1997, 53, 10921-10938. (c) Dı ´az, Y.; El- Laghdach, A.; Matheu, M. I.; Castillo ´n, S. J. Org. Chem. 1997, 62, 1501- 1505. (d) Chao, Q.; Zhang, J.; Pickering, L.; Jahnke, T. S.; Nair, V. Tetrahedron 1998, 54, 3113-3124. (e) Bravo, F.; Kassou, M.; Dı ´az, Y.; Castillo ´n, S. Tetrahedron Lett. 2001, 336, 83-97. (5) For use in cyclopropanation and ring expansion, see: Ramana, C. V.; Murali, R.; Nagarajan, M. J. Org. Chem. 1997, 62, 7694-7703. (6) For use in a novel class of glycosylation based in a [4+2] cycloaddition, see: (a) Capozzi, G.; Dios, A.; Frank, R. W.; Geer, A.; Marzabadi, C.; Menichetti, S.; Nativi, C.; Tamarez, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 777-779. (b) Franck, R. W.; Marzabadi, C. H. J. Org. Chem. 1998, 63, 2197-2208. (7) For the synthesis of thionucleosides from thioglycals, see: Haraguchi, K.; Nishikawa, A.; Sasakura, E.; Tanaka, H.; Nakamura, K. T.; Miyasaka, T. Tetrahedron Lett. 1998, 39, 3713-3716. (8) (a) Wittman, M. D.; Halcomb, R. L.; Danishefsky, S. J. J. Org. Chem. 1990, 55, 1979-1981. (b) Guthrie, R. D.; Irvine, R. W. Carbohydr. Res. 1979, 72, 285-288. ORGANIC LETTERS 2006 Vol. 8, No. 4 673-675 10.1021/ol052866l CCC: $33.50 © 2006 American Chemical Society Published on Web 01/17/2006