Covalent Chemistry and Conformational Dynamics of Topologically Chiral Amide‐Based Molecular Knots

Abstract

The readily available in gram quantities tris(allyloxy)knot of the amide-type 5 (knotane) can be completely and partially deprotected with nBu(3)SnH in the presence of a palladium catalyst resulting in hydroxyknotanes 7-9. These, in turn, react with diethylchlorophosphate giving rise to knotanes equipped with between one and three phosphoryl groups. Sulfonylation of bis(allyloxy)monohydroxyknotane 8 with p-toluenesulfonyl chloride and, following removal of one or two allyl groups from the intermediate monosulfonate 13, give rise to sulfonyloxy-allyloxy-hydroxy- and sulfonyloxy-dihydroxy-knotanes 15 and 14, respectively. This provides a convenient method for the preparation of knotanes with any substitution pattern. All new knotanes have been isolated in preparative amounts and as highly pure substances with an exception of allyloxy-dihydroxyknotane 9. This compound could only be obtained as a mixture with the corresponding monohydroxy-derivative 8. The structures of all synthesized compounds were established by means of FAB and MALDI TOF mass spectrometry, (1)H and (31)P NMR spectroscopy. The triphosphorylated knotane 10 exhibits high solubility in alcohols, allowing its complete enantiomeric resolution with a commercially available chiral HPLC column. (1)H,(1)H DQF-COSY correlation spectroscopy along with H/D exchange experiments and ab initio calculations provided the first detailed (1)H NMR signal assignments of knotanes in [D(6)]DMSO solution. The combination of variable temperature (1)H and (31)P NMR spectroscopy and molecular modeling has been applied to study the conformational behavior of the new knotanes in different solvents. It has been shown that in DMSO solution at room temperature knotanes exist in a relatively rigid nonsymmetrical conformation similar to that found in the solid state while faster conformational exchange leading to the average D(3) symmetrical structure was detected in a number of other solvents.

Stereoselective Synthesis of a Topologically Chiral Molecule: The Trefoil Knot

“…The 1 H-NMR spectrum of 5 shows broad signals at room temperature. We believe that this is due to reptation within the molecule, as observed previously for another molecular trefoil knot [16] . The ESI-MS gives the m/z 1964.22 molecular mass and a number of fragmentation products can be observed too.…”

“…[11] The enantiomers of some of these knots and their derivatives were also resolved by chiral chromatography in a collaborative project between Vögtle's and Okamoto's groups. [12] Two other examples of synthetic knots have been described, [13][14][15][16] including an "open" knotted species constructed around an octahedral metal centre used as template. [14] As far as we know, topologically chiral compounds have never been prepared in a stereoselective way.…”

Knotting and Threading of Molecules: Chemistry and Chirality of Molecular Knots and Their Assemblies

“…The dodecaamide-knotane of general formula 8 [21,[36][37][38][39][40][41] is one of the four isolable cyclic oligomers 8-11 formed in the course of a high-dilution macrocyclization between easily available derivatives of 2,6-pyridinedicarboxylic acid dichloride 12 and the elongated diamines 13 (Scheme 2). Useful insights into the formation of the amide-knotane were Scheme 1.…”

Knotaxane – Rotaxane mit Knoten als Stopper

“…[1] Die anderen Signale sind gleichfalls in Einklang mit den Zuordnungen für mono-Osulfonierte Knotane, über die wir kürzlich berichtet haben. [1,11] Die d,l-Paare des Knotaxans 6 a und der Hantel 5 a konnten nur mithilfe von nicht kommerziellem "Chiralpak AD"-Säulenmaterial [12] getrennt werden, das Tris(3,5-dimethylphenylcarbamoyl)amylose kovalent an einen KieselgelTräger gebunden enthält. Die UV-und CD-Spektren in Abbildung 1 zeigen, dass die Enantiomere von 5 a und 6 a getrennt werden konnten.…”

“…Wir haben kürzlich gezeigt, dass die Löslichkeit von Knotanen durch Einführung bestimmter Substituenten wie FrØchet-Dendrons [9] und Phosphoryl-Gruppen [11] an der Peripherie der Knoten stark beeinflusst wird. 5-(Dimethylamino)naphthalin-1-sulfonyl(Dansyl)-Gruppen, die sowohl lipophil als auch polar sind, schienen in dieser Hinsicht attraktiv.…”