A new three-step general asymmetric synthesis of planar chiral [2.2]metacyclophanes from m-xylenes is described. The strategy employs a regioselective thermodynamic benzylic metalation using LiNK conditions (BuLi, KOtBu, TMP(H)) with in situ oxidative C-C bond formation (with dibromoethane) to produce substituted 1,2-di-m-tolylethanes 1  .1 Repeating the LiNK metalation conditions for the simultaneous metalation of both benzylic positions of 1   and oxidative ring closure provides the achiral 5-substituted [2.2]metacyclophanes 2  .2 Using sBuLi / (-)sparteine as metalation conditions in combination with the ortho-directing properties of the C-5 substituent permits an enantioselective C-4 metalation. Introduction of a diverse set of substituents by reaction with electrophiles directly produces chiral [2.2]metacyclophanes 3 . This first report of an asymmetric synthesis of planar chiral [2.2]metacyclophanes may open the path for their further exploration as chiral ligands and catalysts.1. (a) Fleming, P.; O'Shea, D.F. J. Am. Chem. Soc. 2011  , 133, 1698. (b) Blangetti, M.; Fleming, P.; O'Shea, D.F. J. Org. Chem. 2012  , 77, 2870.2. Blangetti, M.; Fleming, P.; O'Shea, D.F. Beilstein J. Org. Chem. 2011  , 7, 1249.

Asymmetric synthesis and application of planar chiral [2.2]metacyclophanes

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.