Jun Ichi Matsumoto

Medium-sized cyclophanes. Part 18. 5-tert-Butyl-8-substituted [2.2]metaparacyclophanes: preparation, X-Ray diffraction studies, and their treatment with Lewis acids in benzene

The preparation of various 8-substituted 5-tert-butyl[2.2]metaparacyclophanes 8 using the sulfur method, and X-ray diffraction studies of dithia[3.3]metaparacyclophanes 6 and 8-methyl[2.2]metaparacyclophane 1b, are described. AlCl3–MeNO2-catalysed trans-tert-butylation of 8-alkyl- and 8-hydroxy-5-tert-butyl[2.2]metaparacyclophanes 8 in benzene gave the desired 8-alkyl- and 8-hydroxy[2.2]metaparacyclophanes 1 in good yield. However, 5-tert-butyl-8-methoxy[2.2]metaparacyclophane 8c was isomerized to the strainless 5-tert-butyl-8-methoxy[2.2]metacyclophane 13 and this was converted into the tetrahydropyrenes 11 and 12. The mechanism of this reaction is also discussed.

Medium-sized cyclophanes. Part 36. Synthesis and conformational studies of dimethoxy[m.n]metacyclophanes

The synthesis and structure of internally substituted [m.n]metacyclophanes are described. The preparation of tert-butyl[n.2]metacyclophanes 8 was carried out by using the tert-butyl group as a positional protecting group on the aromatic ring. The reaction of l,n-bis(3-chloromethyl-2-methoxyphenyl)alkanes 5 with Na2S in ethanol under high-dilution conditions, followed by oxidation with m-chloroperbenzoic acid, afforded the corresponding thia[n.3]metacyclophane dioxide 7. The pyrolysis of anti-thia[n.3]metacyclophane dioxides 7 gave both the syn- and anti-[n.2]metacyclophane 8 except for the case of anti-thia[10.3]metacyclophane dioxide 7f, which afforded the solely conformationally mobile analogue 8f at room temperature. The solution conformation of [m.n]metacyclophanes is sensitive to the chain length of the bridges. The ring-inversion energy barriers determined by variable-temperature 1H NMR spectroscopy decrease with increasing length of the bridges. In the case of thia[n.3]metacyclophanes 6 and thia[n.3]metacyclophane dioxides 7, [7.3]-analogues 6d and 7d are both conformationally rigid below 140 °C, but [8.3]-analogues 6e and 7e exhibit conformational flipping with coalescence temperatures of –20 °C (ΔGc‡= 12.0 kcal mol–1) and 50 °C (ΔGc‡= 15.6 kcal mol–1), respectively. On the other hand, [n.2]metacyclophanes 8 are conformationally rigid for [7.2]-8d and [8.2]-metacyclophane 8e below 140 °C, but [10.2]metacyclophane 8f exhibits conformational flipping above –20 °C (ΔGc‡= 11.9 kcal mol–1). Demethylation dimethoxythia[n.3]-6 and dimethoxy [n.2]metacyclophanes 8 with BBr3 in dichloromethane afforded the corresponding dihydroxythia[n.3]-9 and dihydroxy[n.2]metacyclophanes 1, respectively. Methylation of the hydroxy groups of dihydroxy[n.2]metacyclophanes 1 led to the conformationally rigid structures, i.e. the fixed conformations such as ‘syn’ and ‘anti’ conformations. The syn : anti ratio of the products is strongly governed by the number of the methylene groups in the bridge. Thus the proportion of syn conformer increases with increasing number of methylene bridges. The template effect of the sodium cation plays an important role in this alkylation for the higher dihydroxy[n.2]metacyclophanes 1c–f which adopt more flexible conformations. Conversion of the hydroxy groups of dihydroxy[10.2]metacyclophane 1f into ethoxy and benzyloxy groups afforded exclusively syn-conformers syn-10a and syn-10b, which are conformationally rigid structures. The assignment of syn and anti conformations was confirmed by 1H NMR analysis.

The preparation and novel [3.3] sigmatropic rearrangement of cyclophanes having a spiro skeleton

Oxidation of dihydroxy[n.2]metacyclophanes 1 with K3[Fe(CN)6] afforded the intramolecular O–C coupling product 2, which has a spiro skeleton in good yield; variable temperature 1H NMR measurements indicated that compounds 2 are interconvertible by a thermal [3.3] sigmatropic rearrangement, and the activation free energies for the [3.3] sigmatropic rearrangement increased with increasing length of the methylene bridge in compounds 2.