Synthesis of Multilayered [3.3](3,5)Pyridinophanes

Abstract

(3,5)pyridinophanes (PyPs) have been synthesized by the (4-tolylsulfonyl)methyl isocyanide (TosMIC) method. The coupling reaction between 3,5-bis[2-isocyano-2-(4-tolylsulfonyl)ethyl]pyridine (TosMIC adduct) and bis(chloromethyl) or tetrakis(bromomethyl) compounds in the presence of sodium hydride in N,N-dimethylformamide or sodium hydroxide and tetrabutylammonium iodide under high-dilution conditions gave the two-layered dione or three-and four-layered tetraones. Wolff-Kishner reduction of the ketones afforded the desired two-to four-layered [3.3](3,5)PyPs. The structure of the dione units take an anti geometry whereas the cyclophane units take a syn geometry in solution.[3.3]Metapyridinophanes (MPyPs) are composed of two pyridine rings and two three-atom bridges connected to them. Among the various types of [3.3]MPyPs, the [3.3](2,6)PyPs have been studied in detail and the 2,11-diaza, 2 dithia, 3 dioxa, 4 and diselena derivatives 5 have been synthesized along with all the carbon parent cyclophanes 6 ( Figure 1). These PyPs have served as ligands for transition-metal complexes, and various kinds of metal complexes have been prepared. 5,7 Their conformational isomerism has also attracted much attention. 8 In contrast, a limited number of [3.3](3,5)PyP are known to date, mainly due to the instability of the coupling precursor, 3,5-bis(halomethyl)pyridine. In our recent preparation of 2,11-diaza[3.3](3,5)PyP, freshly prepared 3,5-bis(chloromethyl)pyridine was used for the coupling reaction. 9 One of the major advantages of the [3.3](3,5)PyPs over the [3.3](2,6)PyPs is the potential ability to form selfassembled supramolecules upon coordination, because the cyclophanes take syn geometry and the nitrogen lone pair electrons can readily coordinate to metals without steric hindrance by the bridges. For example, the formation of the double-decker type 2:2 complexes has been reported in 2,11-diaza-10 and dithia[3.3](3,5)PyPs. 11In previous papers, we reported the synthesis of multilayered [3.3]cyclophanes by the (4-tolylsulfonyl)methyl isocyanide (TosMIC) method (metacyclophanes; MCPs) 12 and (4-ethylphenylsulfonyl)methyl isocyanide (EbsMIC) method (paracyclophanes; PCPs). 13 Therefore, multilayered MCPs incorporating pyridine rings at both ends may form larger supramolecules upon complexation with the transition metals and new types of supramolecules may serve as catalysts, inclusion hosts, and nanometer-scale materials. We now report the synthesis of two-to fourlayered [3.3](3,5)PyPs 1-3 and their structures in solution by 1 H NMR studies. Multilayered [3.3](3,5) PyPs 1-3 were synthesized by theTosMIC method in the critical coupling reaction (Scheme 1). The synthetic key intermediates for the synthesis of multilayered PyPs are bis(chloromethyl)pyridine 4 9 and its TosMIC adduct 6. 3,5-Bis(chloromethyl)pyridine (4) was synthesized by chlorination of 3,5-lutidine with N-chlorosuccinimide in carbon tetrachloride followed by column chromatography on silica gel (n-hexane-EtOAc, 3:1; R f = 0.20) to give 4 in 32% yield. The...

Crystal structure of a four-layered [3.3](3,5)pyridinophane

“…The title compound was prepared as described by Shibahara et al (2008) by a coupling reaction of 5,7,14,16-tetrakis(bromomethyl)[3.3]metacyclophane with 3,5-bis[2-isocyano-2-(tolylsulfonyl)ethyl]pyridine, which afforded four-layered [3.3](3,5)pyridinophane tetraone, which was converted to the four-layered[3.3](3,5)pyridinophane Shibahara et al, 2009) by a Wolff-Kishner reduction. Purification of the crude product by silica gel column chromatography with CH 2 Cl 2 /EtOH (9:1; v/v, R f = 0.53) gave the four-layered pyridinophane (12% isolated yield in two steps).…”

“…This occurs because the metacyclophanes (MCPs) have syn geometries and the nitrogen lone-pair electrons can readily coordinate with metals without steric hindrance being caused by the bridges. We have also described the synthesis of multilayered [3.3]cyclophanes using the (p-tolylsulfonyl)methyl isocyanide method (MCPs; Shibahara et al, 2007) and the (p-ethylbenzenesulfonyl)methyl isocyanide method (paracyclophanes; Shibahara et al, 2008). Multilayered [3.3]MCPs that have a pyridine ring at each end may, therefore, form larger supramolecules when they form complexes with transition metals.…”

A conformational study of [3.3](3,5)pyridinophane

“…The preferred syn geometry of 3 is supported by the deshielded aromatic proton signal (H a : d 7.13, CDCl 3 ) compared to the corresponding proton of the dione 6 (H a : d 6.07, CDCl 3 ) with the anti geometry. 10 The sharp singlets of the aromatic proton (Ha: d 7.22; Hb: d 7.84) and benzylic proton (d 2.75) signals at 20°C suggest a rapid conformational isomerism on the NMR time scale, that is, wobbling of the bridge and ring inversion of the pyridine ring. As the temperature is lowered, both the aromatic and benzylic proton signals broaden, and each aromatic proton signal was resolved into two signals (Ha: d 7.19 and 7.28; Hb: d 7.64 and 7.80).…”

“…10 6 In order to simplify the signals of the trimethylene bridge protons of 3, four deuteriums were introduced into the 2,11-positions (Scheme 1). The dione 6 was converted into the dithioacetal 7 (59%), 11 and subsequent hydrogenolysis with n-Bu 3 SnD in the presence of AIBN produced 3-d 4 (46%).…”