Bis(oxazolines) based on glycopyranosides – steric, configurational and conformational influences on stereoselectivity

In previous studies we found that the asymmetric induction of bis(oxazolines) based on D-glucosamine strongly depended on the steric demand of the 3-O-substituents. To further probe the impact of the 3-position of the pyranose scaffold, we prepared 3-epimerised and 3-defunctionalised versions of these ligands as well as a 3-O-formyl derivative. Application of these new ligands in asymmetric cyclopropanation revealed strong steric and configurational effects of position 3 on asymmetric induction, further dramatic effects of the pyranose conformation were also observed.


General methods
Dry solvents were obtained by distillation over appropriate drying reagents under a nitrogen atmosphere (CH 2 Cl 2 was distilled from calcium hydride), or purchased in dried form from commercial sources (DMF and benzene from Acros, abs. ethanol from Fisher Scientific). All reactions involving reagents sensitive to air and moisture were carried out under a nitrogen atmosphere (glove box and/or Schlenk techniques). Reactions were monitored by TLC on 60 F254 aluminium plates (Merck) with detection by UV light and/or charring with 10% sulfuric acid in ethanol or a mixture of cerium(IV) sulfate and molybdophosphoric acid in 8% sulfuric acid.
Flash chromatography was performed on Merck silica (grain size 40-63 µm). NMR spectra were recorded on an AVS 400 instrument (Bruker) at 400 MHz ( 1 H) or at 100 MHz ( 13 C) respectively. Deuterated chloroform was used as solvent and spectra were calibrated against the residual solvent peaks (CHCl 3 : 7.24 ppm for 1 H and 77 ppm for 13 C). Chemical shifts δ are given in ppm, coupling constants J are given in Hz. Electrospray mass (ESI) spectra were recorded on a Micromass LCT device (Waters). Optical rotations were recorded on a Perkin-Elmer 451 instrument under following standard conditions: Room temperature, wavelength 589.3 nm (sodium D line), cell length 1 dm, solvent and sample concentration (in 10 mg/ml) are given with the individual experiment.
Trifluoromethanesulfonic anhydride (1.28 g, 0.75 mL, 4.54 mmol) was dissolved in dry CH 2 Cl 2 (5 mL) and added slowly to the reaction mixture at −20 °C. The mixture was allowed to warm up to 10 °C and diluted with CH 2 Cl 2 and HCl (1 M). The mixture was washed successively with saturated aqueous NaHCO 3 solution and brine. The organic layer was dried over Na 2 SO 4 and the solvent removed under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: PE/EtOAc 3:1) to yield 9 (1.22 g, 2.13 mmol, 96%) as a colourless foam.
The solvent was removed under reduced pressure and the residue twice co-  Determination of enantiomeric excesses by gas chromatography on a chiral stationary phase: A racemic sample of the product was analysed by GC on the chiral stationary phase to obtain the retention times of both enantiomers. Then an enantiomerically enriched sample was injected and the enantiomeric excess was determined from the resulting chromatogram by peak integration.

Analytical data for the cyclopropanation products
Absolute configurations were assigned by the sign of the optical rotation of the respective compound and comparison with literature data.