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Iron-Catalyzed C—H Insertions: Organometallic and Enzymatic Carbene Transfer Reactions

preprint
submitted on 21.03.2018, 13:12 and posted on 21.03.2018, 16:03 by Katharina J. Hock, Anja Knorrscheidt, Renè Hommelsheim, Junming Ho, Martin J. Weissenborn, Rene M. Koenigs

C—H insertion reactions with organometallic and enzymatic catalysts based on earth-abundant iron complexes remain one of the major challenges in organic synthesis. In this report, we describe the development and application of these iron-based catalysts in the reaction of two different carbene precursors with N-heterocycles for the first time. While FeTPPCl showed excellent reactivity in the Fe(III) state with diazoacetonitrile, the highest activities of the YfeX enzyme could be achieved upon heme-iron reduction to Fe(II) with both diazoacetonitrile and ethyl diazoacetate. This highlights unexpected and subtle differences in reactivity of both iron catalysts. Deuterium labeling studies indicated a C—H insertion pathway and a marked kinetic isotope effect. This transformation features mild reaction conditions, excellent yields or turnover numbers with broad functional group tolerance, including gram-scale applications giving a unique access to functionalized N-heterocycles.

History

Email Address of Submitting Author

rene.koenigs@rwth-aachen.de

Email Address(es) for Other Author(s)

katharina.hock@rwth-aachen.de Anja.Knorrscheidt@ipb-halle.de rene.hommelsheim@rwth-aachen.de junming.ho@unsw.edu.au martin.weissenborn@ipb-halle.de

Institution

RWTH Aachen University, Institute of Organic Chemistry

Country

Germany

ORCID For Submitting Author

0000-0003-0247-4384

Declaration of Conflict of Interest

The authors declare no conflict of interest.

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