Generation of Cryptophanes in Water by Disulfide Bridge Formation

Cryptophanes are receptors consisting of two bridging concave cyclotribenzylene (CTB) subunits. The formation of cryptophanes in basic aqueous solutions (0.1 M MOD; M = Li, Na, K, and Cs) by disulfide bridge formation has been investigated. Two original CTBs, 1H(6) and 2H(6), derived from cyclotriphenolene through the introduction of mercaptomethyl and mercapto substituents, respectively, were synthesized. Cryptophane formation by slow oxygenation of 1(6-) was observed only in the presence of Me4N+ as template, which yielded the diastereomeric forms in a ratio of around 82:18. By contrast, the rigid CTB 2H(6) yielded a cryptophane stereoselectively without a template. Interestingly, air oxidation of a 1:1 mixture of 1(6-) and 2(6-) in the presence of Me4N+ (0.5-1 equiv./1(6-)) in 0.1 m LiOD led to the exclusive formation of the cryptophane complex [(1.1)(6-)superset of+NMe4], (2.2)(6-) being formed only in very minor amounts. No mixed species were detected in the reaction mixtures. The stabilities of the diastereomers of the protonated cryptophanes were calculated in the gas phase by DFT at the omega B97XD 6-311G(d,p) level of theory.