Halogenation of 1,5-Anhydrohex-1-enitols (Glycals). Influence of the C-6 Substituent

The stereochemistry of addition of chlorine and bromine to 3,4-di-O-acetyl-L-rhamnal (1), 3,4-di-O-acetyl-L-fucal (2), and other glycals has been investigated. Variations in the reaction conditions lead to dihalides having different configurations at C-l and C-2. Chlorination in nonpolar solvents appears to proceed via stabilized syn ion pairs, selectively affording cis addition products. The product distribution from the bromination reactions suggests the participation of different ionic intermediates. In both chlorination and bromination, the product distribution is affected by the polarity of the solvent, the structure of the enol ether, and the nature of the halogen. The product distribution in the bromination reactions depends on the electron-withdrawing or -donating effect of the substituent at C-6. This result was interpreted in terms of the effect that the 6-substituent may exert on a nonbonding electron pair of the ring oxygen atom, affecting the stabilization of the carbocation at the anomeric center. The C-6 substituent exerts no significant effect on the chlorination reaction. Changes in the configuration of the substituents of the glycal may also modify the stereochemical course of the reaction. Thus, a change in the orientation of the acetoxy group at C-4 from equatorial (1) to axial (2) influenced the side of attack by halogen upon the double bond, leading to different ratios of cis and trans addition products from 1 and 2.