Nickel-Catalyzed Chemoselective Arylation of Amino Alcohols |
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Authors: | Kathleen M Morrison Dr Charles S Yeung Prof?Dr Mark Stradiotto |
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Institution: | 1. Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. Box 15000, Halifax, Nova Scotia, B3H 4R2 Canada;2. Department of Discovery Chemistry, Merck & Co., Inc., 33 Avenue Louis Pasteur, Boston, MA 02115 USA |
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Abstract: | A systematic evaluation of competitive bisphosphine/Ni-catalyzed C?N versus C?O cross-couplings involving model compounds enabled development of hitherto unknown chemoselective O- and N-arylation of amino alcohols with (hetero)aryl chloride electrophiles, without recourse to protection group chemistry. Use of the CyPAd-DalPhos pre-catalyst C2 enabled particularly challenging O-arylation chemoselectivity in amino alcohols featuring branched primary and secondary alkylamine groups, while selective N-arylation was observed in substrates featuring less-hindered linear alkylamine and aniline reacting groups. Useful reaction scope in the (hetero)aryl chloride was achieved throughout, and the ability to conduct such transformations using benchtop handling of materials is demonstrated. |
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Keywords: | Amino Alcohol Bisphosphine Chemoselectivity Cross-Coupling Nickel |
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