Synthesis of Functionalized Chiral Carbocyclic Cleft Molecules Complementary to Tröger's Base Derivatives

The synthesis of optically pure functionalized cleft molecules derived from dibenzobicyclo[b,f][3.3.1]nona-5a,6a-diene-6,12-dione is reported. These clefts are reminiscent of Tröger's base but contain
clefts with different dimensions and additional carbonyl (or alcohol) groups that may be utilized in
molecular recognition studies. The 2,8-dimethyl and 2,8-dibromo derivatives were synthesized via
an intramolecular Friedel−Crafts acylation and were resolved by chiral HPLC. The 2,8-dinitro
derivative was prepared by regiospecific nitration of dibenzobicyclo[b,f][3.3.1]nona-5a,6a-diene-6,12-dione. The dibromo and dinitro derivatives allow direct access to a range of functionalized
molecular clefts. Palladium-catalyzed coupling of the dibromo derivative afforded the disubstituted
phenyl, anisole, and acetylene derivatives, while reduction of the dinitro derivative and acetylation
provided amino-dione and amide-hydroxyl derivatives. X-ray crystal structures of the dimethyl
12, dibromo 13, di(p-methoxyphenyl) 16, dinitro 18, and dimethyl dinitro 22 derivatives show cleft
angles between the planes between the aromatic rings of 84−104°. The synthetic route, structural
features, and potential for molecular recognition studies of this class of clefts are compared with
those of the more widely studied Tröger's base cleft molecules.