Stereoselective lateral functionalization of monosubstituted [2.2]paracyclophanes by directed ortho-metalation-homologous anionic fries rearrangement

Two efficient routes have been developed for the lateral functionalization of monosubstituted [2.2]paracyclophanes After protection of the ortho site of an O-([2.2]paracyclophanyl) diisopropylcarbamate, an anionic Fries rearr angement resulted in a substitution of the benzylic position to give syn-4- hydroxy-N,N-diisopropyl-5-triethylsilyl-2-[2.2]paracyclophanecarboxamide (4 b) with a syn/anti diastereoselectivity of more than 99:1. An alternate rou te consisted of the direct functionalization of the lateral position of N-t ert-butyl-4-[2.2]paracyclophanecarboxamide (9) by directed metalation. The reaction was found to be highly stereoselective, with only the syn isomer 1 1 being formed.