Enantioselective, Intermolecular Benzylic C–H Amination Catalyzed by an Engineered Iron-Heme Enzyme

• Published in: Nature chemistry Vol. 9; no. 7; pp. 629 - 634
• Main Authors: Prier, Christopher K., Zhang, Ruijie K., Buller, Andrew R., Brinkmann-Chen, Sabine, Arnold, Frances H.
• Format: Journal Article
• Language: English
• Published: 29.05.2017
• ISSN: 1755-4330; 1755-4349
• DOI: 10.1038/nchem.2783

C–H bonds are ubiquitous structural units of organic molecules; while these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst, based on a cytochrome P450 monooxygenase, for the highly enantioselective, intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme’s protein framework confers activity on an otherwise unreactive iron-heme cofactor. The intermolecular amination of C–H bonds is an enabling transformation for the synthesis of nitrogen-containing molecules, yet a challenging activity for chemical catalysts. Here we engineer an iron-based enzyme for this reaction, demonstrating that a protein can confer a difficult new function upon an otherwise unreactive base metal.