Synthesis of ent-ketorfanol via a C-H alkenylation/torquoselective 6? electrocyclization cascade.

ABSTRACT: The asymmetric synthesis of ent-ketorfanol from simple and commercially available precursors is reported. A Rh(I) -catalyzed intramolecular C?H alkenylation/torquoselective 6??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 6??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.

SUBMITTER: Phillips EM 

PROVIDER: S-EPMC4676713 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature