Direct Access to 4,5‐Disubstituted [2.2]Paracyclophanes by Selective ortho‐Halogenation with Pd‐Catalyzed C–H Activation

Abstract A palladium‐catalyzed protocol for the halogenation of [2.2]paracyclophanes by C–H activation is described, and ortho selectivity is achieved with an O ‐methyloxime directing group. Bromination and iodination of the sterically demanding [2.2]paracyclophane proceed in good yields with inexpensive and readily available N ‐halosuccinimides. Deprotection of the O ‐methyloximes yields ortho ‐halogenated aldehydes as attractive intermediates for the modular synthesis of 4,5‐disubstituted [2.2]paracyclophanes. The synthetic value of this protocol was demonstrated by exemplary conversions of the carbaldehyde and halogen site. Additionally, early stage resolution and subsequent bromination/deprotection provides the brominated aldehyde in enantiopure form.