The synthesis and characterization of all diastereomers of a linear symmetrically fused Tris-Tröger's base analogue: new chiral cleft compounds.

The synthesis and characterization of all diastereomers of a linear symmetrically fused tris-Tröger's base analogue are described. The diastereomers are unambiguously assigned as syn-anti 1 a, anti-anti 1 b, and syn-syn 1 c isomers, by using X-ray diffraction analysis and NMR spectroscopy. For the first time, the anti-anti and the syn-syn diastereomers of a linear symmetrically fused tris-Tröger's base analogue have been synthesized. Molecules 1 a and 1 c are new cleft compounds and analysis of compound 1 a in the solid state shows inclusion of one molecule of CH(2)Cl(2) in the larger aromatic cleft, whereas in isomer 1 c disordered solvent molecules are trapped in the extended aromatic cleft. Furthermore, in the solid state, isomer 1 c forms infinite open channels along one of the crystallographic axes and perpendicular to this axis there are infinitely extending "wedged-ravines". Importantly, each of the diastereomers 1 a-c is resistant to inversion at the stereogenic nitrogen atoms under strongly and weakly acidic conditions in the range from room temperature (RT) to 95 degrees C. This observed configurational stability at the stereogenic nitrogens of 1 a-c is unique for analogues of Tröger's base in general to date. Finally, the ratio of cleft compounds 1 a and 1 c significantly increased relative to cavity compound 1 b when ammonium chloride was used as an additive in the Tröger's base condensation to 1 a-c suggesting a templating effect of the ammonium ion.