496848-98-7Relevant articles and documents
Synthesis, reactions and structural features of monofluorinated cyclopropanecarboxylates
Haufe, Guenter,Rosen, Thomas C.,Meyer, Oliver G.J.,Froehlich,Rissanen, Kari
, p. 189 - 198 (2002)
Monofluorinated cyclopropanecarboxylates are available in racemic or optically active form by transition metal-catalyzed reactions of vinylfluorides with diazoacetates. From α-fluorostyrene and tert-butyl diazoacetate in the presence of 2mol% of an enantiopure bis(oxazoline) copper complex, a 81:19 mixture of tert-butyl trans- and cis-2-fluoro-2-phenylcyclopropanecarboxylates was obtained with high enantiomeric excess (ee) of 93 or 89%, respectively. The corresponding racemic ethylesters were used as starting materials for the synthesis of carboxamides, of the cis- and trans-isomers of analogues of tranylcypromine, an anti-depressive drug and several of its homologous fluorinated cyclopropylmethyl and cyclopropylethyl amines. Corresponding enantiopure cyclopropylmethanols and several of their derivatives were synthesized also. Solid state structures of a selection of these compounds were examined by X-ray crystallography. Particularly, the cis-configurated fluorinated phenylcyclopropane derivatives showed extremely close intermolecular C-H···F-C contacts. The shortest of such distances (2.17A) was found in the N-(4-bromophenyl)carbamate of (1S,2R)-(2-fluoro-2-phenylcyclopropyl)methanol.
Synthesis of enantiopure monofluorinated phenylcyclopropanes by lipase-catalyzed kinetic resolution
Rosen, Thomas C.,Haufe, Guenter
, p. 1397 - 1405 (2002)
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.
