Synthesis and intramolecular hydrogen bonding of syn-9-hydroxy-18-substituted [3.3]metacyclophanes

Abstract

Various anti-9-methoxy[3.3]metacyclophane-2,11-diones are exclusively obtained by the coupling reaction of the corresponding 1,3-bis(bromomethyl)benzenes and 2,6-bis[2-isocyano-2-(tolylsulfonyl)ethyl]-4-tert-butylanisole in dimethylformamide (DMF) with an excess of sodium hydride, from which the corresponding syn-[3.3]metacyclophanes (MCPs) are synthesized via anti/syn-isomerization during the Wolff–Kishner reduction. Demethylation of syn-9-methoxy[3.3]MCPs with BBr3 afforded the corresponding syn-9-hydroxy[3.3]MCPs in good yields. The existence of the strong intramolecular hydrogen bonding between the 9-hydroxy group and the 18-substituents, such as F, OH, and OMe groups at the opposing aromatic rings, are observed in solution and in the solid state. A distinct low-field shift of the phenolic OH proton was observed in the 1H NMR spectrum compared with that of the 18-unsubstituted analog. Furthermore, O–H···F through-space coupling was observed.