Synthesis of ent-Ketorfanol via a C-H Alkenylation/Torquoselective 6[pi] Electrocyclization Cascade

The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A RhI-catalyzed intramolecular CH alkenylation/torquoselective 6πelectrocyclization cascade provides a fused bicyclic 1,2-dihydropyridine as a key intermediate. Computational studies were perfor...

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Bibliographic Details
Published in:Angewandte Chemie 2015-10, Vol.127 (41), p.12212
Main Authors: Phillips, Eric M, Mesganaw, Tehetena, Patel, Ashay, Duttwyler, Simon, Mercado, Brandon Q, Houk, Kendall N, Ellman, Jonathan A
Format: Article
Language:ger
Subjects:
Chemistry
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Summary:The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A RhI-catalyzed intramolecular CH alkenylation/torquoselective 6πelectrocyclization cascade provides a fused bicyclic 1,2-dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6πelectrocyclization. The computational results demonstrate that a conformational effect is responsible for the observed selectivity. The ketone functionality and final ring are introduced in a single step by a redox-neutral acid-catalyzed rearrangement of a vicinal diol to give the requisite carbonyl, followed by intramolecular Friedel-Crafts alkylation.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.201505604