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 sulfones derived from glucose, galactose, mannose, cellobiose, and ribose into di-, tri-, and tetra-substituted alkenes is re-

Synthetic applications of exo-glycals, derived from S-glycoside dioxides using the Meyers variant of the Ramberg−Bäcklund rearrangement, are described. These include a formal synthesis of a β-glycosidase inhibitor 12 and an efficient route to spirocyclic glucose derivatives 17 and [a] Scheme 2. exo-Glycals are versatile intermediates for the synthesis of more highly functionalised C-glycosides CHCl 3 )}. Sigmatropic rearrangements involving the enol ether function have recently been described: a Claisen rearrangement of 6-vinyl exo-glycals [12] and a ClaisenϪIreland rearrangement of 2-O-acyl exo-glycals [13] furnish cyclooctene and C-glycan derivatives, respectively. Exomethylenic sugars have also proved to be good substrates for ring-closing olefin metathesis: derivatives of 2a bearing an unsaturated side chain at position 2 have been shown to undergo ruthenium catalysed ring closure to give bicyclic glycosylidene compounds. [14] Postema and Calimente have also exploited this powerful carbonϪcarbon bond-forming process for the preparation of C1-substituted glycals [15a] and C-linked disaccharides. [15b] The phenyl-substituted exo-glycal derivative 2b is accessible in high yield and good stereoselectivity from the tandem halogenation-RambergϪBäcklund rearrangement of benzyl sulfone 1b (Scheme 1). We decided to explore the elaboration of this substrate (Scheme 3). When hydroboScheme 3. HydroborationϪoxidation of exo-glycal 2b to give the known C-glycoside 11Eur.

Two novel routes to C-linked glycosyl amino acids are described; the first involves elaboration of an exo-glycal and subsequent Ramberg-Bäcklund rearrangement of a sulfone intermediate to give, after functional group manipulation, a protected C-glycosyl serine, while the second uses hydroboration-Suzuki coupling of the same exo-glycal to produce ultimately the corresponding C-glycosyl asparagine analogue.

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In recent years, there has been increasing interest in the preparation and properties of C-disaccharides. Their hydrolytic stability and potential enzyme-inhibitory properties make such compounds attractive as unnatural mimetics and therefore as synthetic targets.[1] As a result, a number of methodologies have been developed for the synthesis of this class of compound. [2,3] As part of an ongoing program [3, 4] to investigate applications of the Ramberg-Bäcklund Reaction (RBR), [5] we recently reported a RBR approach to C-linked disaccharides and employed it to prepare C-isotrehalose, Chomoisotrehalose, and methyl C-gentiobioside.[3] However, the route involved the initial preparation of protected monosaccharides and their subsequent conversion into thioglycosides and then thioglycoside dioxides and was therefore rather lengthy. Herein we report the rapid synthesis of a range of novel C-glycosides and C-disaccharides which commences from readily available protected monosaccharides 1 and involves a tandem Horner-Wadsworth-Emmons (HWE)/ conjugate-addition C-glycosidation followed by a tandem halogenation-RBR sequence, utilizing Meyers variant of the RBR [6] (Scheme 1). Thus, the plan was to prepare glycosylsulfonylmethyl-HWE reagents 2 and then carry out the condensation giving the vinyl sulfone intermediate 3 which would be expected [7] to undergo conjugate cyclization in situ to produce sulfone 4. Subsequent Meyers-type in situ asulfonyl halogenation followed by tandem RBR should then produce alkene 5 which could be elaborated/deprotected to provide a range of novel C-disaccharides.Proof-of-principle studies were carried out using the benzylsulfonylphosphonate reagent 6[8] and diisopropylidene mannofuranose 7 (Scheme 2). We were delighted to find that the HWE/conjugate-addition process proceeded in a reasonable 64 % unoptimized yield using sodium hydride in THF giving the C-glycoside 8 stereoselectively as the b-isomer (J 1,2 = 3.6 Hz). Sulfone 8 was next subjected to the halogenation-RBR sequence. The standard Meyers conditions [6a] only gave a 48 % yield of 9 but use of the supported KOH-CBr