Yasuo Dobashi

Enantioselectivity of Hydrogen-Bond Association in Liquid-Solid Chromatography

Abstract Liquid chromatographic resolutions of enantiomers induced by molecular associations whose main driving force is the action of weak hydrogen bonds are described. The hydrogen-bond association potential was first demonstrated through the optical resolution of racemic N-acylated amino acid esters using a chiral stationary phase (CSP) (N-acyl-L-valylamino)propyl silica gel. Following this preliminary study, application was made of the chiral mobile phase additive (CMPA) on which the fundamental structure of the chiral graft of CSP is reproduced, to the resolution of the above solute enantiomers in liquid-solid chromatography. The addition of N-acetyl-L-valine tert-butylamide to the nonaqueous mobile phase solvent of a silica gel column successfully brought about this optical resolution; by this method, a novel and more effective chiral resolving agent was found. Two types of chiral additives derived from a chiral skeleton (R,R)-tartaric acid were found capable of resolving various kinds of enantiomer...

Enantiomer resolution of d- and l-α-amino acid derivatives by supercritical fluid chromatography on novel chiral diamide phases with carbon dioxide

The rapid resolution of racemic N-4-nitrobenzoylamino acid isopropyl esters was accomplished without the loss of enantioselectivity by supercritical fluid chromatography (SFC) on novel chiral valine-diamide phases with carbon dioxide and a polar methanol modifier. In each stationary phase, a chiral moiety was anchored to the silica gel surface by a long decamethylene spacer. The enantioselectivity in SFC was comparable to that in liquid chromatography using 2-propanol-n-hexane. The time required for analysis was less than 5 min, and the range of enantiomer resolution (Rs) was 10.8-1.25. On using 2-propanol in place of methanol the separation was improved, but was accompanied by a decrease in column efficiency. The end-capping effect of the remaining surface silanols on enantiomer resolution is discussed.

Direct resolution of enantiomers by liquid chromatography with the novel chiral stationary phase derived from (R,R)-tartramide

Abstract The synthesis of the novel chiral stationary phase (CSP) derived from (R,R)-tartramide and direct resolution of a series of β-hydroxycarboxylic acid derivatives on this CSP are described.

Hydrozirconation of alkenyloxirane derivatives: Preparation of cycloalkylmethanols

Abstract Cyclopentyl and cyclopropylmethanol derivatives were efficiently prepared through a chemoselective hydrozirconation reaction of (1-butenyl)oxirane and vinyloxirane with Cp 2 ZrHCl. However, the attemped reaction of (1-pentenyl)oxirane or (1-propenyl)oxirane failed to yield cyclohexyl or cyclobutylmethanols. The ring formation was stereospecific and proceeded with the inversion of the configuration at the reacting oxirane carbon. The origin of stereospecificity and the stereoselectivity in the formation of cyclopropylmethanols was presumed by the approach of the Schwartz reagent from the less hindered site of the stable gauche -conformer of the vinyloxirane compound in the transition state. (Cyclopropylmethyl)amine derivatives were also prepared by the treatment of vinylaziridine derivatives with Cp 2 ZrHCl.

Chiral recognition conducted by tartaric acid derivatives in nonaqueous media

Abstract Chiral recognition of hydroxycaboxylic acid, amino acid and 1,2-diol derivatives using diastereomeric complexation based on hydrogen bond with L(+)-N,N′-diisopropyl-tartramide (DIPTA) is described.

Highly Selective Stereodivergent Synthesis of Separable Amide Rotamers, by Using Pd Chemistry, and Their Thermodynamic Behavior

By using Pd chemistry, a highly selective stereodivergent synthesis of separable amide rotamers was achieved. Allylation of 2,4,6-tri-tert-butylanilides using a pi-allyl-Pd catalyst gave N-allylated anilides with moderate-to-excellent Z-rotamer selectivity (Z/E = 3 to > 50). The Z-rotamer selectivity depends considerably on the substituent on the anilide substrates. On the other hand, the E rotamers of N-allylated 2,4,6-tri-tert-butylanilides were obtained with almost complete selectivity (E/Z > 50) through O-allylation of 2,4,6-tri-tert-butylanilides and the subsequent Pd(II)-catalyzed Claisen rearrangement of the resulting O-allyl imidate. The prepared anilide rotamers changed to equilibrium mixtures in which the E rotamer was the major isomer when heated in toluene.

Chiral Recognition Based on Hydrophobic Entanglement of Enantiomers with Chiral Diamide Phases in Aqueous Media

Abstract Chiral stationary phases (CSPs) from N-(10-undecenoyl)-L-valine tert-butylamide (1) and N-(5-hexenoyl)-L-valine tert-butylamide (2) were each found to afford a hydrophobic interfacial phase by which hydrogen-bond association could be induced for the resolution of enantiomeric N-acylated amino acid esters in aqueous phase liquid chromatography. This was shown using the fluorescence fine structure of pyrene sorbed on the interfacial phase in three kinds of wetting water-organic solvent mixtures: water-methanol, water-acetonitrile, and water-tetrahydrofuran (THF). The intensity ratios of pyrene vibronic emission peaks gave strong indication of changes in microenvironment polarity around pyrene as a function of overlaying solvent composition. Increase in organic solvent concentration enhanced polarity due to solvent intercalation in the interfacial phase. A less polar organic solvent, such as THF, was caused to become distributed to a greater degree within the phase than a more polar methanol and con...

A New Twisted Dual Hydrogen Bond Acceptor Featuring Amidine Functionality for Chiral Recognition: A High Level of Enantioselection of Diol Derivatives

Abstract The C 2 amidine derivative ( S,S )- 1 , as a twisted chiral dual acceptor for hydrogen bonding, was designed and synthesized. Enantioselective binding between ( S,S )- 1 and a series of diol enantiomers was investigated by NMR spectroscopy. High enantioselection above 1.0 kcal/mol was achieved in CDCl 3 . The association mode based on dual N⋯HO interactions was confirmed by intermolecular NOEs.

CHIRAL RECOGNITION OF 1,1'-BI-2-NAPHTHOL ENANTIOMERS BY TWISTED AMIDINE DERIVATIVES : RATIONAL DESIGN OF A HIGHLY ENANTIOSELECTIVE RECEPTOR

Abstract Clarification of the molecular structures of diastereomeric complexes relevant to the enantioselective dual N···HO binding between the chiral C 2 amidine derivative (S,S)- 1 and 1,1′-bi-2-naphthol 2 in CDCl 3 afforded the structural factor determining the sense of observed enantioselection. This insight into chiral recognition was successfully applied to the design of a new twisted dual hydrogen bond acceptor (S,S)- 3 that exhibited a higher level of enantioselectivity toward 2 .