Synthesis of functionalized difluoronaphthalenes by regioselective C—H functionalization of 2,3-difluoronaphthalene

2,3-Difluoronaphthalene ( 1 ) was selectively converted into 1-methyl-, 1,4-dimethyl-, 1-acetyl-, 1-acetyl-4-methyl-, 1-formyl-, and 1-carboxyl-substituted 2,3-difluoronaphthalenes using lithiation with BuLi as a key step. Nitration and bromination of compound 1 predominantly gave 6,7-difluoro-1-nitronaphthalene and 1-bromo-6,7-difluoronaphthalene, respectively. Regioselectivity of acylation of compound 1 and 2,3-difluoro-1,4-dimethylnaphthalene with AcCl in the presence of AlCl3 dramatically depended on the order of mixing and addition of the reagents. Under the optimized conditions, the yields of 1-(6,7-difluoronaphthalen-1-yl) ethanones and 1-(6,7-difluoronaphthalen-2-yl)ethanones reached 68–93%.