Stereoselective synthesis of meta- and three-bridged cyclophanes with intramolecular [2 + 2] photocycloaddition by using the steric effect of methoxyl group

• Published in: Tetrahedron Vol. 50; no. 42; pp. 12159 - 12184
• Main Authors: Okada, Yukihiro, Ishii, Fuyuhiko, Kasai, Yoshinori, Nishimura, Jun
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 1994
• Subjects: conformation; Cyclophane; photocycloaddition; regioisomer; stereoselectivity; torsional angle; photocycloaddition; torsional angle; regioisomer; conformation; Cyclophane; stereoselectivity
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/S0040-4020(01)89568-5

Dimethoxy[n.2]metacyclophanes 9 (n=2, 3, 4, 5, and 6) and 10 were stereoselectively obtained in 61 – 87% yields by means of[2+2] photocycloaddition. Their conformations, when n=3-6, are exclusive of syn, while the dimethoxy[2.2]metacyclophane exists as a mixture of syn and anti isomers with the ratio of 4:3. After their Birch reduction, [n.4]metacyclophanes 11 (n=2 - 6) were successfully obtained in 59 – 94% yeilds. Their conformations, when n=2-4 are of anti or n=5 and 6 are of syn. Dihydroxy [n.4]metacyclophanes 16 (n=2 - 6) and dihydroxy[n.2]metacyclophanes 17 (n=4, 5, and 6) were obtained in 93 – 100% and 78 – 95 % yields, respectively, after the demethylation of methoxyl groups. The conformation of 16 and 17 is the same as that of corresponding dimethoxymetacyclophanes. The acidity of phenolic group in 16 and 17 is low like monomeric phenol. After olefination and vinylation via triflate 18, the metacyclophanes 19 and 21 gave the three-bridged [n.2.2](1,3,4)cyclophanes 20 and 22 stereoselectively in 65 – 67% and 42 – 86% yields, respectively, under photoirradiation. The two cyclabutane rings of 20 and 22 face oppositely each other as confirmed by NOESY experiments and the structures are most stable among possible four ones according to the MM2 calculation. And also, three-bridged phanes 22 were converted to [n.4.4](1,3,4)cyclophanes 23 in 61 – 79% yields by the Birch reduction. Another regioisomeric three-bridged n.2.2](1,3,5)cyclophanes 28 were also obtained stereoselectively as only one isomer in 31 – 78% yields with photocycloaddition by using the steric effect of methoxyl group. The configuration of cyclobutane rings relative to methoxyl groups was confirm to be anti by NOESY experiments. The torsional angle of methoxyl groups on cyclophanes was estimated from 13C NMR chemical shifts. The angles of metacyclophanes 9, 10, and 11 are 10 – 25° and those of three-bridged cyclophanes 28 are about 54° which is the largest one among those ever reported. Dimethoxy[n.2]metacyclophanes 9 and 10 were stereoselectively obtained by means of [2 + 2] photocycloaddition. The regioisomeric three-bridged [n.2.2](1,3,4)cyclophanes 20 and 22 or [n.2.2](1,3,5)cyclophanes 28 were also obtained stereoselectively as only one isomer with photocycloaddition. The torsional angle of methoxyl groups on cyclophanes was estimated from 13C NMR chemical shifts.