Gram-Scale Robust Synthesis of 1-Chloro-2,3-dimethyl-4-phenylnaphthalene: A Promising Scaffold with Three Contiguous Reaction Positions

A three-step reaction sequence for the gram-scale synthesis of 1-chloro-2,3-dimethyl-4-phenylnaphthalene was developed. (i) Stereoselective dichlorocarbene addition to methyl angelate afforded methyl (1S*,3S*)-2,2-dichloro-1,3-dimethylcyclopropane-1-carboxylate (78% yield, >98% purity, distillation). (ii) Addition reaction of two molar amounts of PhLi afforded (1S*,3S*)-2,2-dichloro-1,3-dimethylcyclopropyldiphenylmethanol (81% yield, >98% purity, recrystallization). (iii) Key SnCl4-mediated benzannulation produced the desired product (83% yield, >98% purity, recrystallization) with three contiguous reaction sites. Five derivatization examples including benzylic reactions and cross-couplings at the pendant Cl-position are demonstrated. Some relevant distinctive benzannulations are also discussed.