Formation of meta-Substituted Phenols by Transition Metal-Free Aromatization: Use of 2-Bromocyclohex-2-en-1-ones.

ABSTRACT

Addition of Grignard or other organometallic reagents to 2-halocyclohex-2-en-1-ones bearing an alkyl or aryl group at C-5, followed by mild acid treatment and exposure to 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) at room temperature, generates meta-substituted phenols in which the newly introduced meta substituent originates from the Grignard reagent. The range of effective organometallic reagents includes alkyl, allyl, alkynyl, aryl, and heteroaryl compounds including those with fluorine substituents. The initial halocyclohexenone can be deprotonated at C-6 and reacted with carbon, fluorine, or sulfur electrophiles before the Grignard addition so as to generate highly substituted phenols.