Use of mixed Li/K metal TMP amide (LiNK chemistry) for the synthesis of [2.2]metacyclophanes

• Marco Blangetti,
• Patricia Fleming and
• Donal F. O'Shea

Beilstein J. Org. Chem. 2011, 7, 1249–1254, doi:10.3762/bjoc.7.145

• substituted m-xylenes is described. The strategy employs a selective benzylic metalation and oxidative C–C bond formation for both synthetic operations. Regioselective benzylic metalation is achieved using the BuLi, KOt-Bu, TMP(H) (2,2,6,6-tetramethylpiperidine) combination (LiNK metalation conditions) and

• oxidative coupling with 1,2-dibromoethane. The synthetic ease of this approach compares favourably with previously reported methods and allows for ready access to potentially useful planar chiral derivatives. Keywords: benzylic metalation; LiNK chemistry; [2.2]metacyclophane; oxidative coupling; planar

• reaction. Examples of such challenges include the selective aryl metalation of arenes containing more than one directing group (DG), arene metalation in positions not ortho to the directing group, or the identification of reaction conditions to achieve selective benzylic metalation of substituted toluenes