Tetra‐tert‐butyltrioxabicyclo[3.3.1]nonadienedicarboxylic Acid: Optical Resolution, Absolute Configuration and Application in Chiral Discrimination

Abstract

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.

Molecular cleft or tweezer compounds derived from trioxabicyclo[3.3.1]nonadiene diisocyanate and diacid dichloride

“…As in the crystal structure, the two chains are held in this orientation by 2 Å hydrogen bonds. The calculated structure of the diester 3 (Figure S4, Supporting Information File 1 ) is also in very good agreement with the previously determined crystal structure [ 3 ], but unlike the structures of 4 and 5 described above, the two ester moieties in compound 3 point away from each other with an angle of approximately 120° between them.…”

“…This endows them with claw-like molecular cleft or tweezer properties as manifested in enhanced abilities to extract selected alkali and alkaline earth metal and rare earth ions. The ready availability of diisocyanate 1 and diacid dichloride 2 [ 1 – 3 11 ] paves the way for the synthesis of many other types of compounds with hairpin turns and parallel pendant chains.…”

“…1 ) was reported recently [ 1 ]. This and several other derivatives of the unique 2,6,9-trioxabicyclo[3.3.1]nonadiene (“bisdioxine”) system, including the diacid, the diacid dichloride 2 [ 2 ] and the diethyl ester 3 [ 3 ] are readily synthesized from the stable dimer of dipivaloylketene.…”

From dipivaloylketene to tetraoxaadamantanes

“…The treatment of the dimeric ketene 3 with nucleophiles allowed the preparation of numerous derivatives of the unique 2,6,9-trioxabicyclo[3.3.1]nonadiene (bisdioxine) system 8 – 13 , namely the monoamides 8 , the diacid 11 , the diacid dichloride 12 , and the esters 9 , 10 and 13 [ 18 – 19 ] ( Scheme 3 ). The mechanism of formation of these derivatives is summarized in Scheme 4 .…”

“…It is worth noting that the bisdioxines exhibit axial chirality [ 21 ], as has been demonstrated by 1 H NMR spectroscopy using the optically active shift reagent Eu(hfc) 3 [ 19 ]. The enantiomers of the dicarboxylic acid 11 have been separated by flash chromatography of their diastereomeric salts with 1-phenethylamine, and the structures of the acids and ethyl esters were determined by X-ray crystallography [ 19 ].…”