Tetra-tert-butyltrioxabicyclo[3.3.1]nonadienedicarboxylic acid: Optical resolution, absolute configuration and application in chiral discrimination

The enantiopure bridged bis-dioxine 4, a dissymmetric dicarboxylic acid exhibiting axial chirality, can easily be synthesized and serve as host for separating and/or transporting chiral guest molecules. Racemic 4 gives with (R)- and (S)-1-phenylethylamine the corresponding pure diastereomeric salts 7 and 8. The absolut configuration of the diacid 4 in the diastereomeric salt 7 containing (R)-1-phenylethylamine was confirmed to be R by X-ray crystal structure analysis, which also confirmed its concave nature. Release of the acid-sensitive pure enantiomers (R)-4 as well as (S)-4 was achieved conveniently by use of dry flash-chromatography on silica. The CD spectrum shows a positive Cotton effect of the (S)-enantiomer at 206 nm. The enantiomeric purity was proved by 1H NMR discrimination of the diastereomeric salts with (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamine as the base. The dicarboxylic acid (R)-4 can be used as chiral auxiliary as demonstrated by the difficult resolution of racemicN,N-di-tert-butyl-1,2-bis(4-methoxyphenyl)ethane-1,2-diamine 9.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)