Highly Diastereo- and Enantioselective Synthesis of Nitrile-Substituted Cyclopropanes by Myoglobin-Mediated Carbene Transfer Catalysis
Dr. Ajay L. Chandgude
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Rudi Fasan
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627 USA
Search for more papers by this authorDr. Ajay L. Chandgude
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627 USA
Search for more papers by this authorCorresponding Author
Prof. Dr. Rudi Fasan
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, NY, 14627 USA
Search for more papers by this authorGraphical Abstract
One for many: A chemobiocatalytic strategy involving myoglobin-catalyzed olefin cyclopropanation in the presence of ex situ generated diazoacetonitrile enables the efficient synthesis of a broad range of nitrile-substituted cyclopropanes with high diastereo- and enantioselectivity. The enzymatic product could be further elaborated to afford a variety of functionalized chiral cyclopropanes.
Abstract
A chemobiocatalytic strategy for the highly stereoselective synthesis of nitrile-substituted cyclopropanes is reported. The present approach relies on an asymmetric olefin cyclopropanation reaction catalyzed by an engineered myoglobin in the presence of ex situ generated diazoacetonitrile within a compartmentalized reaction system. This method enabled the efficient transformation of a broad range of olefin substrates at a preparative scale with up to 99.9 % de and ee and up to 5600 turnovers. The enzymatic product could be further elaborated to afford a variety of functionalized chiral cyclopropanes. This work expands the range of synthetically valuable, abiotic transformations accessible through biocatalysis and paves the way to the practical and safe exploitation of diazoacetonitrile in biocatalytic carbene transfer reactions.
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