A Family of Routes to Substituted Phenols, Including Meta-Substituted Phenols

A new family of routes to substituted phenols has been developed. 2-Bromo-3-methoxycyclohex-2-en-1-ones are readily deprotonated at C-6, and the resulting anions react smoothly with a variety of electrophiles; treatment with DBU in PhMe at room temperature then results in efficient aromatization to benzene derivatives of a regiochemically defined substitution pattern. This sequence affords phenolic azides (ArN₃), sulfides (ArSR, ArSAr′), selenides (ArSePh), alcohols [ArCH­(OH)­R], amino derivatives [ArCH­(NHSO₂Ar′)­R), and 1,2-benzenediols. A complementary set of substitution patterns is obtained by DIBAL-H reduction or reaction with a Grignard reagent before aromatization; the latter process gives compounds in which the newly introduced substituent is meta to the phenolic hydroxyl.