Trifluoromethyl-substituted cyclopropanes constitute attractive building blocks in medicinal chemistry and drug discovery, as they combine the conformational rigidity of cyclopropyl rings with the beneficial features of fluorinated substituents. An efficient method for the asymmetric synthesis of trifluoromethyl-substituted cyclopropanes by means of myoglobin-catalyzed olefin cyclopropanation reactions in the presence of 2-diazo-1,1,1-trifluoroethane (CF3CHN2) as the carbene donor will be presented. These biocatalytic transformations were carried out using a two-compartment reaction setup in which ex situ generated gaseous CF3CHN2 is processed by engineered myoglobin catalysts expressed in E. coli cells. A variety of trans-1-trifluoromethyl-2-arylcyclopropanes were obtained in high yields and excellent diastereo- and enantioselectivity. Furthermore, mirror-image forms of these chiral cyclopropanes were obtained using myoglobin variants featuring divergent stereoselectivity.

Asymmetric synthesis of trifluoromethyl-substituted cyclopropanes via myoglobin-catalyzed transfer of trifluoromethylcarbene

255th National Meeting (2018)

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