FULL PAPER A New Route to exo-Glycals Using the Ramberg2Bäcklund Rearrangement Frank K. Griffin, [a] Duncan E. Paterson, [a] Paul V. Murphy, [a] and Richard J. K. Taylor* [a] Dedicated to Professor Jean-Franc¸ois Normant on the occasion of his 65th birthday Keywords: Carbohydrates / Sulfones / Rearrangements / Enol ethers A new route to exo-glycals 4 is described in which glycosyl sulfones 3 are subjected to the Meyers variant of the Ramberg-Bäcklund rearrangement. The conversion of sul- fones derived from glucose, galactose, mannose, cellobiose, and ribose into di-, tri-, and tetra-substituted alkenes is re- Introduction The discovery of the fundamental roles played by oligo- saccharides, and their lipid and protein conjugates, at a mo- lecular level has stimulated the enormous growth in carbo- hydrate research over the last three decades. [1] Crucial to the expansion of knowledge in this area has been the contri- bution of synthetic chemists in providing practical quanti- ties of pure, naturally occurring carbohydrates and, perhaps more significantly, chemically modified mono- and oligo- saccharides. Particularly useful in this context are exo-gly- cals (formally 2,5- or 2,6-anhydro-1-deoxy-hex- or -hept-1- enitols) which are not only valuable in biological investi- gations per se, [2] but are also important synthetic interme- diates owing to the scope of the enol ether functional group for further elaboration. [3] Herein we present a novel syn- thetic route to exo-glycals employing the Ramberg2 Bäcklund rearrangement [4,5] as the key step. The methods for exo-glycal synthesis may be divided into two main categories: those in which the carbon skeleton is constructed first and then subjected to an elimination reac- tion, [6] and those in which unsaturation is incorporated dur- ing C2C bond formation such as in the olefination of sugar lactones using the Tebbe [7] or Petasis [8] reagent, or Wittig chemistry. [9] In a novel route recently reported by To´th and Somsa´k, [10] 2,5- and 2,6-anhydroaldose tosylhydrazones are transformed, in a Bamford2Stevens reaction, into glycosyl- methyl carbenes, which then undergo a spontaneous 1,2- hydrogen shift to give exo-methylenic sugar derivatives. The ease of preparation and the chemical stability of al- kyl and aryl thioglycosides, combined with their ready ac- tivation to the corresponding sulfonium species, has re- [a] Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK Fax: (internat.) 144-1904/432-543 E-mail: rjkt1@york.ac.uk Eur. J. Org. Chem. 2002, 130521322  WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002 14342193X/02/040721305 $ 17.501.50/0 1305 ported. Preliminary mechanistic studies of this process are also described. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002) sulted in their routine application as glycosyl donors in O- glycoside synthesis. [11] The use of thioglycoside derivatives as precursors to glycosyl anions has also been extensively investigated, and is among the many approaches described in a recent review on this subject. [12] Due to the long- standing interest in sulfone and Ramberg2Bäcklund chem- istry within our own research group, [13] we also recognised the potential of such compounds: we envisaged a thioglyco- side S,S-dioxide (glycosyl sulfone) being subjected to a Ramberg2Bäcklund rearrangement to introduce an exo- C2C double bond at the anomeric position (Scheme 1). Initial studies established that this was indeed a feasible transformation, the scope of which appeared considerable with regard to both the saccharide and aglycon portions. [14] Shortly after we disclosed our own results, similar findings were reported by Belica and Franck. [15] In the following sec- tions the synthesis of a variety of glycosyl sulfones and their conversion into exo-glycals are described. Scheme 1. Generic representation of the transformation of glycosyl sulfones into exo-glycals via a Ramberg2Bäcklund rearrangement. PG 5 protecting group Results and Discussion Synthesis of Glycosyl Sulfones Thioglycosides may be conveniently prepared from a variety of common glycosyl donors, for example from the