Resolution and Novel Reactions of 4-Hydroxy[2.2]paracyclophane

The resolution of racemic 4-hydroxy[2.2]paracyclophane (1) by fractional crystallization of the diastereomeric esters 3 with (1S)-(−)-camphanic acid and the determination of the absolute configurations of (R)- and (S)-4-hydroxy[2.2]paracyclophanes by X-ray diffraction have been carried out. The Friedel−Crafts oxaloylation of 1 with AlCl3 was found to occur with formation of both ortho- and para-hydroxy[2.2]paracyclophanylglyoxylic acids, whereas in the presence of TiCl4, quantitative formation of 2,3-dioxo-2,3-dihydrofurano[4,5-d][2.2]paracyclophane (8) as a product of an unusual cooperative C- and O-acylation was observed. Replacement of the OH group in the substrate for OCH3 (compound 18) changes the regioselectivity of the oxaloylation, which now occurs with formation of a para-substituted α-diketone 19. A novel technique for the synthesis of 4-formyl-5-hydroxy[2.2]paracyclophane (FHPC, 15) involving stereoselective reduction of 8 followed by oxidative cleavage of the intermediate diol 14 is also presented.