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Highly Diastereoselective and Enantioselective Olefin Cyclopropanation Using Engineered Myoglobin‐Based Catalysts
Author(s) -
Bordeaux Melanie,
Tyagi Vikas,
Fasan Rudi
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201409928
Subject(s) - cyclopropanation , myoglobin , enantioselective synthesis , carbene , olefin fiber , reactivity (psychology) , chemistry , combinatorial chemistry , electrophile , catalysis , aryl , organic chemistry , medicine , alkyl , alternative medicine , pathology
Using rational design, an engineered myoglobin‐based catalyst capable of catalyzing the cyclopropanation of aryl‐substituted olefins with catalytic proficiency (up to 46 800 turnovers) and excellent diastereo‐ and enantioselectivity (98–99.9 %) was developed. This transformation could be carried out in the presence of up to 20 g L −1 olefin substrate with no loss in diastereo‐ and/or enantioselectivity. Mutagenesis and mechanistic studies support a cyclopropanation mechanism mediated by an electrophilic, heme‐bound carbene species and a model is provided to rationalize the stereopreference of the protein catalyst. This work shows that myoglobin constitutes a promising and robust scaffold for the development of biocatalysts with carbene‐transfer reactivity.