Enantioselective Total Synthesis of (+)-Incargranine A Enabled by Bifunctional Iminophosphorane and Iridium Catalysis.

Autor: Miller AAM; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK., Biallas P; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK., Shennan BDA; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK., Dixon DJ; Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Jan 08; Vol. 63 (2), pp. e202314308. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1002/anie.202314308
Abstrakt: 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.
(© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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