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Direct Access to 4,5 ‐ Disubstituted [2.2]Paracyclophanes by Selective ortho ‐Halogenation with Pd‐Catalyzed C–H Activation
Author(s) -
Kramer Joshua J. P.,
Yildiz Ceylan,
Nieger Martin,
Bräse Stefan
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201301723
Subject(s) - halogenation , chemistry , enantiopure drug , catalysis , selectivity , steric effects , palladium , aldehyde , chemoselectivity , combinatorial chemistry , medicinal chemistry , organic chemistry , enantioselective synthesis
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.