Regioselective Synthesis of 4,7,12,15-Tetrasubstituted [2.2]Paracyclophanes: A Modular Route Involving Optical Resolution

A practical synthetic method for preparing bis-(para)-pseudo-ortho and bis-(para)-pseudo-meta type 4,7,12,15-tetrasubstituted [2.2]paracyclophanes is reported. Regioselective double Rieche formylation was successfully applied to the corresponding dibromo[2.2]paracyclophanes under slightly modified conditions. Aldehydes reacted in an unknown direction with Rieche formylation agents, dichloromethyl methyl ether and titanium(IV) tetrachloride, leading to the formation of benzal chlorides. Formylated products were obtained after hydrolysis of these benzal chloride derivatives. Optical resolution was performed with the diastereomer method and (R-P)-4,12-dibromo-7,15-diformyl[2.2]paracyclophane was successfully obtained in an enantiomerically pure form (99 % ee). Their synthetic utility is demonstrated with some exploratory transformations to access corresponding differently functionalized tetrasubstituted [2.2]paracyclophane derivatives.