The first one step synthesis of Z-methoxy-5-alkoxy-2.S-dihydrofurans (Za-i) is reported by reacting the commercially available 2.5-dimethoxy derivative (1) with alcohols Unexpectedly the use of thiophenol and of us-2,4-but-2-enediol leads to Z-tixyl phenyl thioether (4) and cr.s-?-propenal-.3dioxep-S-ene (5). respectively 0 1998 Elsevier Science Ltd. All rights reserved
The widespread occurence of substituted dihydro and tetrahydrofuran rings as substructures in an unusually large number of natural products', has promoted considerable interest in the development of synthetic routes to these compound classes. The commercially available 2,5-dimethoxy-2,5-dihydrofuran 1, represents a useful" polyfunctionalised CJ synthon that seems to be an interesting starting point for building these skeletons. In a previous paper we studied the possibility of substituting only one of the two methoxy groups present in 1 with a sulphonic moiety, thus obtaining a more important target molecule.' In this paper we report a general new methodology to gain non-symmetric 2-methoxy-5-alkoxy-2,5dihydrofurans (2) which are useful intermediates for further synthetic transformations.
In a general procedure 0.0 1 mol of the alcohol 3a-i was reacted with a twofold excess of starting material 1, in CHzCll (300 ml), in the presence of a catalytic amount of toluene p.sulfonic acid. The reaction was conducted in refluxing CH$.Il? in a Dean Stark apparatus to distil the azeotropic CH:Cl: i MeOH mixture.
After removing the solvents (150 ml), the residue was quenched by the addttion of anhydrous K2COI and after the usual workup, the crude 2 (US /runs mixture) was obtained (See Table I).
High yields were obtained when a non hindered alcohol is employed. Surprisingly, when phenols or carboxylic acids are used instead of the alcoholic substrate, no reaction takes place. On the contrary, 2-fury1 phenyl thioether (4) is quantitatively recovered (Scheme I) employing thiophenol as a nucleophile The use of L./S-1 ,4-but-2-ene diol (1 ! 3 molar rate = 2,1), gives os-2-propenal-I ,3dioxep-5-ene (4) (Scheme 1) in 50% overall yield.
Compound 4 is a monoprotected trrm.v-unsaturated dialdehyde and is a useful CJ building block, which has so far only been obtained with difficulty.
Compound 5, to the best of our knowledge, is not available in only one step. The operational simplicity and the possible further synthetic transformations of compounds 2a-i are noteworthy.