TETRAHEDRON LETTERS Tetrahedron Letters 44 (2003) 3631–3635 Pergamon Synthesis of -C -glycosides via tandem Tebbe methylenation and Claisen rearrangement H. Yasmin Godage and Antony J. Fairbanks* Dyson Perrins Laboratory, Oxford University, South Parks Road, Oxford OX13QY, UK Received 7 February 2003; revised 28 February 2003; accepted 14 March 2003 Abstract—A variety of -C -glycosides may be accessed in an entirely stereoselective fashion from 3-OH glycal esters, by way of the tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. In contrast with previous studies in the corresponding -series, careful control of conditions for Claisen rearrangement is required in order to avoid loss of integrity of anomeric stereochemistry; thermal rearrangements are best carried out in xylene in a sealed tube. © 2003 Elsevier Science Ltd. All rights reserved. The synthesis of C -glycosides 1 remains a significant occupation of the synthetic community. 2 This may be as part of natural product total synthesis, or in order to furnish glycomimetics as tools for glycobiology or as potential therapeutic agents. In particular, stereocon- trolled access to a wide variety of C -glycosides would provide materials for biological screening programs, which may shed further light on the proposed ability of C -glycosides to act as non-hydrolysable mimics of their natural O -linked counterparts. 3 As part of our ongoing studies into the development of an approach designed at allowing access to a wide variety of C -glycosides in a parallel synthetic manner, we recently reported 4 the use of glucal derived carbohy- drate esters to allow access to a variety of -C -gly- cosides in high yield and with complete control of anomeric stereochemistry. Herein we report studies allowing synthetic access to the corresponding -C -gly- cosides, again by use of a tandem reaction sequence involving Tebbe methylenation 5 of glycal esters fol- lowed by Claisen rearrangement. 6 The synthesis of the corresponding -C -glycosides nec- essarily entails the use of glycal esters derived from allose, which is epimeric at the 3-position to glucose. To this end we undertook the synthesis of the known 4,6-O -benzylidene protected allal 1 and the correspond- ing C-2 methyl substituted derivative 2, following litera- ture procedures. 7 In addition the corresponding 4,6-O -silyl protected compound 3 was itself accessed from allal 4 8 by regioselective silylation by treatment with di-tert -butylsilyl ditriflate in DMF at low tempera- ture (77% yield, Scheme 1). Treatment of glycal 1 with benzoyl chloride and cata- lytic DMAP in pyridine furnished the benzoate ester 5a, acetylation with acetic anhydride in pyridine yielded the acetate 5b, whilst treatment with either palmitic acid or Boc protected 4-amino butyric acid, together with DCC and catalytic DMAP, correspondingly gave the palmitic 5c and amino butyric esters 5d, respectively. Similarly glycal 2 was converted into its benzoate 6 by treatment with benzoyl chloride, whilst silyl protected glycal 3 was converted into palmitic ester 7. Methylenation of all esters proceeded smoothly by treatment with an excess Scheme 1. Reagents and conditions : (i) t Bu 2 Si(OTf) 2 , DMF, -40°C to rt, 77%. Keywords : C-glycosides; carbohydrates; glycals; Tebbe reagent; Claisen rearrangement. * Corresponding author. Tel.: +441865275647; fax: +441865275674; e-mail: antony.fairbanks@chem.ox.ac.uk 0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved. doi:10.1016/S0040-4039(03)00710-X