53531-34-3Relevant articles and documents
NMR Structure Determination of Ion Pairs Derived from Quinine: A Model for Templating in Asymmetric Phase-Transfer Reductions by BH4- with Implications for Rational Design of Phase-Transfer Catalysts
Hofstetter, Christine,Wilkinson, Patricia Stone,Pochapsky, Thomas C.
, p. 8794 - 8800 (1999)
The solution structures of ion pairs formed by quarternary ammonium ions derived from quinine alkaloid with small hard anions (BH-4 or Cl-) in CDCl3 have been characterized by nuclear magnetic resonance methods. Structural observations have been correlated with the sense of asymmetric induction observed in the phase-transfer reduction of 9-anthryl trifluoromethyl ketone by borohydride (BH-4) when catalyzed by the quaternary N-benzylquinine ammonium ion. From interionic nuclear Overhauser effects (NOEs), it appears that the BH-4 ion occupies two of the four trigonal pyramidal sites formed by substituents of the quarternary nitrogen of the catalyst cation. One of these sites is in close proximity to the cation's hydroxyl group that is strictly required for asymmetric induction in the model reaction, while the other site is near the vinyl group on the cation. The vinyl group does not appear to be important for determining the sense or extent of asymmetric induction. Using energy-minimized structures derived from NMR data, it was predicted that the N-(9-methyleneanthryl)quinine - quarternary ammonium catalyst would give improved asymmetric induction in the model reaction due to a preferred anion occupancy at the site near the hydroxyl group. An improvement in enantiomeric excess (ee) is observed using the anthryl-modified catalyst, and NMR studies on the modified catalyst confirm the predicted change in anion binding site occupancies. The changes in site occupancies determined by NMR can be fitted to a simple kinetic model that correctly predicts the extent of change in ee.
Ultrasound-Controlled Chiral Separation of Four Amino Acids and 2,2,2-Trifluoro-1-(9-anthryl)ethanol
Lee, Jae Hwan,Ryoo, Jae Jeong
, p. 146 - 149 (2019/02/07)
Chiral separation of 4-hydroxyphenylglycine, phenylglycine, tryptophan, methionine, and 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE) was performed under ultrasound reduction at room temperature and high temperature (50 °C). At high temperature (50 °C), both α and Rs were improved slightly under ultrasound reduction as compared to those under non-ultrasonic and ultrasonic irradiation (50 watt/L) conditions. Even at low temperatures, the largest α was observed under ultrasound reduction conditions, except in the case of methionine. However, at low temperature, Rs was reduced under ultrasound (50 watt/L) irradiation, but was improved under ultrasound reduction rather than under the continuous ultrasonic irradiation. Similar to the fact that gradient elution (based on solvent polarity) can improve α, ultrasound reduction can improve α and Rs. Ultrasound reduction is demonstrated to aid the rapid separation of chiral compounds with improved resolution, especially, at high temperatures. Although chromatographic separation using ultrasound has been rarely dealt with until now, ultrasound can be used as an external field in chromatography.
Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State
Hirose, Daisuke,Isobe, Asahi,Qui?oá, Emilio,Freire, Félix,Maeda, Katsuhiro
supporting information, p. 8592 - 8598 (2019/06/13)
An unprecedented three-state switchable chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) was developed using a helical poly(phenylacetylene) bearing a chiral (R)-α-methoxyphenylacetic acid residue as the pendant (poly-1). The left- and right-handed helical conformations were induced in poly-1-based CSP upon coordination with a catalytic amount of soluble sodium and cesium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts (MBArF), respectively, which are soluble in the HPLC conditions [hexane-2-propanol (95:5, v/v)]. The switch between the two different helical states of poly-1 can be easily achieved by rinsing the poly-1-based CSP with MeOH and the subsequent addition of the proper MBArF salt. Using this dynamic helical CSP, we demonstrate how changes on the orientation of the secondary structure of a chiral polymer (right-handed, left-handed, and racemic helices) can alter and even invert the elution order of the enantiomers. This study was done without adding chiral additives or changing the mobile phase, which could produce changes on the retention times and make it more difficult to determine the role of the secondary structure during the chiral recognition process.
Ultrafast chiral separations for high throughput enantiopurity analysis
Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
supporting information, p. 509 - 512 (2017/01/13)
Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
