Combining Stereoselective Enzyme Catalysis with Chirality‐Assisted Synthesis in Tribenzotriquinacene Chemistry

Abstract

The stereoselective synthesis of enantiomerically pure single‐wing‐functionalized tribenzotriquinacenes using the enzyme CAL‐B was successfully extended towards operating on a multi‐gram scale. Based on the ( P )‐tribenzotriquinacene‐2‐carbaldehyde ( P )‐ 6 obtained in >99 % ee , the hitherto unknown ( P )‐2‐hydroxy‐ and ( M )‐2‐hydroxy‐3‐iodo‐TBTQ derivatives ( P )‐ 9 and ( M )‐ 10 were prepared in optically pure form. The bowl‐shaped ortho ‐iodophenol ( M )‐ 10 was subjected to a twofold crosswise Ullmann‐type condensation to give, albeit in low yield (10 %), the 1,4‐dioxine 5 , in which two TBTQ bowls are fused exclusively in a syn ‐bi‐concave orientation, thus demonstrating a new example for a chirality‐assisted synthesis. The corresponding Ullmann condensation of the racemic TBTQ‐ ortho ‐iodophenol rac ‐ 10 furnished the respective anti ‐bis‐TBTQ‐dioxine 11 as the major diastereomer together with the syn ‐isomer 5 in the same total yield and in a 11/5 ratio of at least 4. The two diastereomeric bis‐TBTQ‐dioxines show minor but significant differences in most of the characteristic 1 H‐NMR chemical shifts. The solid‐state structure of the syn ‐dimer 5 , determined by X‐ray diffraction, was found to consist of pairs of host–guest complexes, [ 5· CH 2 Cl 2 ] 2 , with pronounced face‐to‐face orientation of the bi‐concave host molecules.