496849-06-0Relevant academic research and scientific papers
Synthesis of enantiopure monofluorinated phenylcyclopropanes by lipase-catalyzed kinetic resolution
Rosen, Thomas C.,Haufe, Guenter
, p. 1397 - 1405 (2007/10/03)
All four stereoisomers of (2-fluoro-2-phenlycyclopropyl)methanol were synthesized using Amano PS lipase-catalyzed acylation and transesterification as key steps. Copper(I)-catalyzed cyclopropanation of α-fluoro styrene with ethyl diazoacetate and chromatographic separation gave diastereomerically pure cyclopropane carboxylates, which were then reduced with LiAlH4. Whereas the enzymatic acylation gave low selectivities for trans-configured alcohols (E=13) using different acyl donors, the corresponding cis-diastereomers were obtained with high enantiomeric excesses (E >200). Additionally, kinetic resolution of different racemic esters of (2-fluoro-2-phenlycyclopropyl)methanol was achieved by lipase-catalyzed transesterification employing Amano PS in the presence of ethanol and the selectivities from this process were found to be comparable to those observed in the enzymatic acylation. The absolute configurations of the enantiomers were confirmed by X-ray structural analysis of the corresponding enantiopure p-bromophenyl carbamates. In addition, the stereochemistry of the product from the asymmetric cyclopropanation of α-fluoro styrene with a chiral bis(oxazoline) copper(I) catalyst was similarly determined.
