Enantioselective Total Synthesis of (+)-Incargranine A Enabled by Bifunctional Iminophosphorane and Iridium Catalysis |
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Authors: | Anna A M Miller Dr Phillip Biallas Benjamin D A Shennan Prof Dr Darren J Dixon |
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Institution: | Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA UK |
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Abstract: | Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step. |
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Keywords: | Biomimetic Synthesis Desymmetrisation Hemiaminals Organocatalysis Total Synthesis |
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