Tryptamine Synthesis by Iron Porphyrin Catalyzed C−H Functionalization of Indoles with Diazoacetonitrile
Katharina J. Hock
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorAnja Knorrscheidt
Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Search for more papers by this authorRenè Hommelsheim
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorDr. Junming Ho
School of Chemistry, University of New South Wales, Sydney, NSW, 2052 Australia
Search for more papers by this authorCorresponding Author
Jun.-Prof. Dr. Martin J. Weissenborn
Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle (Saale), Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Rene M. Koenigs
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorKatharina J. Hock
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorAnja Knorrscheidt
Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Search for more papers by this authorRenè Hommelsheim
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorDr. Junming Ho
School of Chemistry, University of New South Wales, Sydney, NSW, 2052 Australia
Search for more papers by this authorCorresponding Author
Jun.-Prof. Dr. Martin J. Weissenborn
Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), Germany
Institute of Chemistry, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 2, 06120 Halle (Saale), Germany
Search for more papers by this authorCorresponding Author
Prof. Dr. Rene M. Koenigs
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Search for more papers by this authorGraphical Abstract
An iron porphyrin catalyst furnishes acetonitrile-functionalized indole derivatives by C−H functionalization reactions of protected and unprotected indole heterocycles with diazoacetonitrile. This process streamlines the synthesis of valuable tryptamines for applications in total synthesis and drug discovery.
Abstract
The functionalization of C−H bonds with non-precious metal catalysts is an important research area for the development of efficient and sustainable processes. Herein, we describe the development of iron porphyrin catalyzed reactions of diazoacetonitrile with N-heterocycles yielding important precursors of tryptamines, along with experimental mechanistic studies and proof-of-concept studies of an enzymatic process with YfeX enzyme. By using readily available FeTPPCl, we achieved the highly efficient C−H functionalization of indole and indazole heterocycles. These transformations feature mild reaction conditions, excellent yields with broad functional group tolerance, can be conducted on gram scale, and thus provide a unique streamlined access to tryptamines.
Supporting Information
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