Oxa-bridged cyclophanes featuring thieno[2,3-b]thiophene and C2-symmetric binol or bis-naphthol rings: synthesis, structures, and conformational studies

Oxa-bridged cyclophanes 4/6 and 8/10 featuring thieno[2,3-b]thiophene ring and binol or bis-naphthol have been synthesized. The structures are assigned by 2D NMR data and the identity of 4 is also independently established by a single X-ray crystallography. From dynamic NMR analysis, the Arrhenius energy of activation ΔG# for bridge inversions in 4 and 6 was calculated to be 15.3 and 12.9 kcal/mol, respectively. A higher ΔG# for 4, relative to the ester free 6 is attributable to the steric compression stemming from C2/C5 ester substituents to the bridge inversion processes. While the methylene bridges undergo inversion in 4 and 6, the naphthyl–naphthyl pseudo-rotation appears to be restricted even at higher temperatures. This is supported by retention of the optical purity of the chiral (−) 4 under thermal condition. For the case of bis-naphthol cyclophane 8, we observed the flipping of both the –OCH2– and the naphthyl–CH2–naphthyl bridges with ΔG# of ca. 11.4 kcal/mol. However, the ester free cyclophane 10 remained conformationally mobile even at −55 °C and its ΔG# was assumed to be <11.4 kcal/mol. The presence of an extra –CH2– linker in bis-naphthol cyclophanes 8/10 renders them relatively more conformationally mobile compared to binol cyclophanes 4/6, possessing a rigid naphthyl–naphthyl geometry.