1,2-Cyclic sulfite and sulfate furanoside diesters: improved syntheses and stability Christopher Hardacre * , Ivano Messina, Marie E. Migaud * , Kerry A. Ness, Sarah E. Norman School of Chemistry and Chemical Engineering, David Keir Building, Stranmillis Road, Queen’s University, Belfast BT9 5AG, UK article info Article history: Received 1 April 2009 Received in revised form 20 May 2009 Accepted 4 June 2009 Available online 10 June 2009 Keywords: Cyclic-sulfite Cyclic-sulfate Carbohydrates Ionic liquids abstract The facile syntheses of 1,2- and 3,5-cyclic sulfite and sulfate furanoside diesters were conducted in molecular solvents and ionic liquids in the presence of immobilised morpholine. Molecular solvents and ionic liquids performed similarly with regards to overall yields. However, the use of ILs allowed for the reactions to be carried out under atmospheric conditions and showed good recyclability. Additionally, increases in product stability was achieved in ILs over organic solvents, in particular, in bis{(tri- fluoromethanesulfonyl)imide} and trispentafluoro-ethyltrifluorophosphate-based ionic liquids, which were also excellent media to control the hydrolysis of thionyl chloride and sulfuryl chloride. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction Thionyl chloride (SOCl 2 ) and sulfuryl chloride (SO 2 Cl 2 ) are ex- tensively used in industry for the manufacture of materials ranging from herbicides, drugs and dyestuffs to thermoplastics, surfactants and electrolytes. 1,2 In organic synthesis; they are primarily used as chlorination reagents, 2,3 while the reactivity of their respective cyclic sulfodiester derivatives is often compared with that of ep- oxides. 4,5 One limitation to the use of SOCl 2 and SO 2 Cl 2 arises from their high reactivity towards moisture. Similarly, cyclic sulfite/sul- fate esters have had limited applications due to problems associ- ated with their syntheses 4,6,7 (e.g., difficulties in controlling cyclisation vs chlorination), as well as their variable reactivity to- wards nucleophiles. 8,9 For example, there are currently only two reported procedures used to prepare 1,2-cyclic sulfites from 1,2- diols. These involve thionyl chloride or N,N 0 -thionyl diimidazole in pyridine under anhydrous and temperature controlled condi- tions. 8,10 Similarly, this chemistry is not applicable to cyclic sulfates which are prepared from the cyclic sulfite precursors, via oxidation with ruthenium tetroxide, thus limiting their potential usage es- pecially within an industrial setting. 5 These issues are further ex- acerbated in the case of partially protected sugar 1,2-diols which do not behave as standard diols, as the stereochemistry of anomeric position (alpha and beta configuration at C-1 of the sugar) controls the sulfite/sulfate formation, reactivity and stability, especially to- wards water. 11 This is particularly relevant as 1,2-cyclic sulfite and sulfate derivatives of carbohydrates have the potential to be ver- satile synthetic precursors to modified nucleosides, C-nucleosides and any derivatives where a ring opening via a nucleophilic sub- stitution at the C-1 position of the sugar results in the regio- and stereo-selective introduction of the aglycon unit. Therefore, if the synthetic and stability problems related to these sulfur-containing reagents could be overcome, cyclic sulfites and sulfates would find a wider range of applications in organic synthesis and large scale productions, in particular in C-nucleoside chemistry. Herein, we report a simple procedure for which reaction and work-up condi- tions have been optimised in order to maximise conversion and minimise furanosyl cyclic sulfoester decomposition. Additionally, we have investigated the possibility of using non-molecular sol- vents in order to achieve higher conversions/yields by providing a stabilising media. 2. Results and discussion 2.1. Synthesis of cyclic sulfites and sulfates in ILs and molecular solvents To date, the syntheses of cyclic sulfites from diols has to be carried out under strictly anhydrous conditions, with or without the use of triethylamine or pyridine as base 4,6 and this has resulted in varied success. Cyclic sulfates are commonly obtained by mild oxidation of the sulfite parents using Sharpless’ conditions re- quiring the use of heavy metals. 12–14 In general, direct syntheses of cyclic sulfates from diols and SO 2 Cl 2 generate several side products (competition between chlorination, multiple sulfurylation and cy- clic sulfate formation) and average yields. 11 Only one report * Corresponding authors. Tel.: þ44 2890 974339/4592; fax: þ44 2890 974687. E-mail addresses: c.hardacre@qub.ac.uk (C. Hardacre), m.migaud@qub.ac.uk (M.E. Migaud). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2009.06.013 Tetrahedron 65 (2009) 6341–6347 Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet