Synthesis Of 1-Naphthols Via Copper-Catalyzed Cascade Reaction Of 2-Halogenated Acetophenones

1-Naphthols are not only important fine chemical intermediates but also building blocks for drug development and natural products synthesis. Thus,1-naphthols have been widely applied in the synthesis of dyes, perfumes, and chiral catalysts.In this paper, we will describe synthesis of 1-naphthols via copper-catalyzed cascade reaction of 2-halogenated acetophenones. The main contents are shown as follows:The cascade reaction of o-bromoacetophenone, o-iodoacetophenone, o-chloroacetophenone was chosen as models to optimize the reaction conditions such as catalyst, solvent, base, and temperature. We found that the best result was obtained when the reaction was treated with 10 mol% CuI as catalyst, N,N-dimethylformamide (DMF) as solvent, and NaO'Bu as base at 60? for o-bromoacetophenone,30? for o-iodoacetophenone, 100? for o-chloroacetophenone. Under optimized conditions, the cascade reaction of 2-halogenated acetophenones proceeded with the yield of o-bromoacetophenone achieving 76%, o-iodoacetophenone achieving 67%, o-chloroacetophenone achieving 58%. The reacion was also founded to be suitable for vairous functional group-substituted o-bromoacetophenones and o-iodoacetophenones, and a variety of new 1-naphthols were synthesized by this way.