Synthesis and Chiral Self-Sorting of Spirobifluorene-Containing Boronate Ester Cages

2,2’-Functionalization induces axial chirality within the orthogonal aromatic scaffold of 9,9’-bispirofluorene. By implementing boronic acids at these positions, well-suited precursors for chiral boronate ester cages are generated. As a key intermediate, (P)-9,9’-bispirofluorene-2,2’-bistriflate (P)-5 was synthesized via a four-step sequence of twofold Friedel-Crafts acylation, Baeyer-Villiger oxidation, hydrolysis, and triflate formation. Chiral resolution was achieved via chiral HPLC for the dihydroxy intermediate. In a modular manner, Pd-catalyzed borylation or cross-coupling afforded either diboronic acid (P)-B* or elongated derivative (P)-B*^Ph possessing additional phenylene spacers. For both enantiomerically pure linkers, reaction with hexahydroxy tribenzitriquinacene A in THF under water-removing conditions afforded isoreticular chiral organic cages (P,P,P)-A₂B*₃ and (P,P,P)-A₂B*^Ph₃. Both cages possess a chiral trigonal-bipyramidal geometry and were characterized by ¹H, ¹³C and DOSY NMR spectroscopy and MALDI-TOF mass spectrometry. Chiral self-sorting of the bispirofluorene precursors was investigated by reactions of A with racemic linkers rac-B* and rac-B*^Ph. For shorter linker rac-B*, quantitative self-sorting into a racemic mixture of (P,P,P)-A₂B*₃ and (M,M,M)-A₂B*₃ occurred. For elongated derivative rac-B*^Ph however, the increased flexibility introduced by the phenylene extension resulted in much lower selectivity and self-recognition. Instead a more complex product mixture was obtained and the racemic mixture of A₂B*^ph₃ was isolated in much lower yield of around 20%. Semiempirical PM6 calculations for both homo- and heterochiral cages and macrocyclic intermediates allowed for an estimation of macrocyclic strain energies and provided in-depht insight into cage formation pathways and self-sorting properties.