Resolution Approaches Toward Enantiopure Planar Chiral 7‐bromo‐4‐hydroxy [2.2]paracyclophane

The resolution of racemic planar chiral 7‐bromo‐4‐hydroxy [2.2]paracyclophane was first achieved through the formation of epimeric esters derived from N ‐phtalimide L ‐isoleucine. Two successive crystallization steps, followed by saponification, enabled the isolation of the ( R P ) enantiomer in enantiopure form (ee > 99%) and in 33% overall yield. In contrast, the opposite ( S P ) enantiomer could only be obtained with a moderate enantiomeric excess of 46%. To overcome this limitation, an alternative strategy based on an early‐stage resolution process was developed. This method relied on the separation of the two enantiomers of racemic 4‐hydroxy [2.2]paracyclophane by high‐performance liquid chromatography with a Daicel Chiralpack IA column, followed by regioselective bromination. This sequence produced both enantiomers of the targeted disubstituted [2.2]paracyclophane, which were isolated in pure enantiomeric form and obtained in good overall yields.