Synthesis of Naphthaleman Family Utilizing Regiocontrolled Benzannulation: Unique Molecules Composed of Multisubstituted Naphthalenes

The naphthaleman family, a set of uniquely designed visual molecular structures comprising multisubstituted naphthalenes, was synthesized utilizing regiocontrolled benzannulation as a key step. The naphthaleman family possesses a common naphthalene body with a head comprising the 3,4-methylenedioxy group, symmetrical or unsymmetrical right and left arms, and two alkynyl legs. The synthesis involves six C–C bond-forming reaction sequences. (i) syn-Stereoselective gem-dichlorocyclopropanation of methyl angelate (86%). (ii) Acylation with ArMgBr (three examples, 60–91% yield). (iii) Stereocontrolled introduction of the 3,4-methylenedioxyphenyl group (three examples, 67–92% yield). (iv) Crucial regiocontrolled benzannulation to construct a common body segment (71–73% yield). (v) Two Suzuki–Miyaura cross-couplings to install the right or left arms (first-stage route: four examples, 77–93% and second-stage route: four examples, 42–90% yield). (vi) Double alkynylation to insert two legs (first-stage route: four examples, 61–77% yield and second-stage route: sole example, 83% yield). The four core members were produced through both first-stage and second-stage routes, with the second-stage approach demonstrating superiority over the first-stage approach. One of the members was alternatively synthesized by switching the installation order of the right and left arms, and identical twin members were produced by high-performance liquid chromatography chiral separation. The most stable conformations of two naphthaleman family members were calculated by Spartan software.