Host-Guest Complexation. 52. Bridged and Chiral Hemispherands

The synthesis, binding properties, and configurational stability of 10 new chiral hemispherand hosts containing the quaterphenyloxy framework are reported, as well as the crystal structures of free hosts 1, 3, 4, and 10 (Chart I) and six complexes of 1. Hosts 1 and 2, although chiral and strong binders, are configurationally unstable due to the relatively low barriers to ring inversions of their CH₃OC₆H₃and EtOC₆H₃parts at ordinary working temperatures. Host 3 is configurationally stable due to the inability of the PhCH₂OC₆H₃parts to undergo ring inversion. This host is a relatively poor binder in CDCl₃at 25 °C of Li⁺, Na⁺, K⁺, Rb⁺, Cs⁺, NH₄⁺, CH₃NH₃⁺, and (CH₃)₃CNH₃⁺picrates, in spite of the fact that its crystal structure shows it to be beautifully organized with all oxygens turned inward and all benzyls turned outward. Hosts 4-6 contain extra bridges in addition to the parent 18-membered macrorings. They are configurationally stable and are relatively strong binders. The presence of CH₃groups in the four positions para to the quaterphenyloxy moiety in 5 produced an increase in binding compared to 4 without the CH₃groups from 0.4 to 1.8 kcal mol^-1(Δ(-ΔG°) values), depending on the guest. A crystal structure of 4 showed all of its oxygens' unshared electron pairs to be turned inward. Host 5 was obtained in an enantiomerically pure state. Hosts 5 and 6, whose oxygen-bridging units are CH₂CH₂CH₂and 1,2-CH₂C₆H₄CH₂, respectively, provided similar -ΔG° values for binding the eight cations. Host 7, containing three chiral elements, was found to undergo ring inversion of its four EtOC₆H₃groups at working temperatures, whereas 8, containing four C₆H₅CH₂OC₆H₃groups, was configurationally stable. As with 3, the presence of the C₆H₅C-H₂OC₆H₃groups markedly depressed its binding properties. Without exception, peak binding for the 18-membered ring hosts (1-8) involved NaPic as guest. Hosts 9-12 all have 21-membered macrorings incorporating a quateraryloxy and either a cis-2,5-tetrahydrofuran or a 2,6-pyridine ring bridging unit to give seven heteroatom binding sites. The crystal structure of free 10 shows it is not highly preorganized for binding. Compounds 11 and 12 are diastereomers, which combine the chiral elements of the cis-2,5-tetrahydrofuran unit and an additional 1,2-CH₂C₆H₄CH₂oxygen-bridging unit. Hosts 9,11, and 12 show peak binding with KPic and 10 with CsPic. The highest K_a(Na⁺)/K_a(K⁺) ratio (150) was observed for 7, and the highest K_a(K⁺)/K_a(Na⁺) ratio (2500) was observed for 8 (K_aare association constants, M^-1). These hemispherands are better binders of cations than the corands but poorer than the spherands, cryptands, or cryptahemispherands.