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 1H‐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·CH2Cl2]2, with pronounced face‐to‐face orientation of the bi‐concave host molecules.