Synthesis of ent‐Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade. Issue 41 (17th August 2015)

• Record Type: Journal Article
• Authors: Phillips, Eric M.; Mesganaw, Tehetena; Patel, Ashay; Duttwyler, Simon; Mercado, Brandon Q.; Houk, Kendall N.; Ellman, Jonathan A.
• Is Part Of: Angewandte Chemie international edition. Volume 54:Issue 41(2015)
• Page Start: 12044
• Page End: 12048
• Publication Date: 2015-08-17
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201505604
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The asymmetric synthesis of <italic>ent</italic>‐ketorfanol from simple and commercially available precursors is reported. A Rh^I‐catalyzed intramolecular CH alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1, 2‐dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6π electrocyclization. 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.</p> </abstract>