The alkaline stability of (5Z)-7-([2RS,4RS,5SR]-4-o-hydroxyphenyl-2-trifluoromethyl-1,3-dioxan-5-yl)hept-5-enoic acid, ICI 185282. A remarkable intramolecular hydride transfer from a trifluoromethyl substituted carbon atom

Abstract

The kinetics of hydrolysis of (5Z)-7-([2RS,4RS,5SR]-4-o-hydroxyphenyl-2-trifluoromethyl-1,3-dioxan-5-yl)hept-5-enoic acid, ICI 185282 (1a), have been studied. At low pH the compound undergoes conventional acid-catalysed hydrolysis of the dioxane ring. However, under alkaline conditions, a second reaction is observed. Studies by NMR show that this process involves a quite unexpected intramolecular hydride transfer from a carbon atom carrying a strongly electronwithdrawing trifluoromethyl substituent. Additional studies on closely related compounds are reported and a mechanism involving a ring-opened quinone methide intermediate is proposed.