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Published on: December 29, 2016
Solvent Effects on the Chemo- and Site-Selectivity of Transition Metal-Catalyzed Nitrene Transfer Reactions:
Robert M Ward1, Yun Hu1, Noah P Tu2
1Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706, USA.
Abstract:
Transition metal-catalyzed, non-enzymatic nitrene transfer (NT) reactions to selectively transform C-H and C=C bonds to new C-N bonds are a powerful strategy to streamline the preparation of valuable amine building blocks. However, many catalysts for these reactions use environmentally unfriendly solvents that include dichloromethane, chloroform, 1,2-dichloroethane and benzene. We developed a high-throughput experimentation (HTE) protocol for heterogeneous NT reaction mixtures to enable rapid screening of a broad range of solvents for this chemistry. Coupled with the American Chemical Society Pharmaceutical Roundtable (ACSPR) solvent tool, we identified several attractive replacements for chlorinated solvents. Selected catalysts for NT were compared and contrasted using our HTE protocol, including silver supported by N-dentate ligands, dinuclear Rh complexes and Fe/Mn phthalocyanine catalysts.
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