Tetrahedron Letters,Vo1.26,No.22,pp 2653-2654,1985 0040-4039/85 $3.00 + .OO Printed in Great Britain 81985 Pergamon Press Ltd. GLYCO-ORGANIC SUBSTRATES IN ORGANIC SYNTRRSIS. PREPARATION OF A WATER SOLWLE BUTADIRNYL-ETHER AND ITS USE IN AQUROUS CYCLOADDITION. Andre Lubineau* and Yves Queneau. Institut de chimie moleculaire d'0rsay. Laboratoire de chimie Organique Multifonctionnelle, associe au C.N.R.S. (U-A. N0462), Bat. 420, Universite Paris-Sud, 91405 Orsay CEDEX. Abstract : A chiral water-soluble butadienyl-ether containing free glucose as hydrophilic moiety was synthesized and used in aqueous cycloaddition reaction with methacrolein to afford through pure endo transition state, only two diastereoisomers from which the sugar could be removed by enzymatic hydrolysis. Polar solvents has been known for a long time to increase stereospecificity in Diels-Alder reactions 1,2* More recently, Breslow3 and Griecol reported aqueous cycloadditions with spectacular rate enhancements. The concentration of diene in water seemed to be crucial and the results depended on the reactants, indicating perhaps different origins of the effects of water in this type of cycloaddition. High concentrations could be achieved using carboxylate groups as the hydrophilic moiety, but this functionnality involves pH restrictions and is certainly not without effect on the energetic balance of the reaction. Moreover, this functionnal group suffers from the fact that it forms a permanent substituent in the products. We propose as a general tool for organic syntheses in aqueous solution, a sugar-assisted solubilization of organic substrates in water. This concept, widely used in Nature, has allowed us also to take advantage of enzymatic catalysis in water, and affords new possibilities in organic synthesis in addition to the use of enzymes in organic solvents or biphasic systems when erratic results may obtain. We describe here, as a model of glyco-organic substrate, the chiral water-soluble butadienyl ether 2 (scheme I). The formation of aldehyde 2 was stereoselective to give only the p-D-configuration5, but the Wittig reaction could be conducted in two different ways. Starting from the p- anomer 2, the reaction gave either the pure p-anomer 1 at -78OC or a mixture with the o(-anomer predominant (cl/p =3) at 25°C. The diene f, obtained by deacetylation of compound 1 reacted with methacrolein6 in water in 3.5h at 25'C whereas the acetylated derivative 1. required 15 days at 60°C in toluene. We chose methacrolein for the stereochemical stability of its adduct, to avoid further thermodynamical equilibration. In fact, of the four possible adducts, a mixture of only two, was obtained in a 60/40 ratio (as determined by 400 MHz N.M.R.) from which the major diastereoisomer (m.p. 151°C, (oO$," +77' (c 0.8, CH2C12)) was separated by cristallisation from ether after complete acetylation. The overall yield for the three steps starting from compound 1 to the mixture of the two acetylated adducts, 5b and 6b, was 90%. The stereochemical course of the reaction was established after hydrogenation on palladium on 2653