Streamlined Stereoselective Entry to (-)-Quinagolide and to 3-Substituted Octahydrobenzo[ g ]-Quinolines.

A very short stereoselective synthesis of enantiomerically pure (3 S , 4a S , 10a R ) - quinagolide has been developed. The key steps involved are a copper-catalyzed regioselective arylation of ( S )-epichlorohydrin with 1,6-dimethoxynaphthalene and a diastereoselective trans -reduction of a cyclic enamine intermediate. The possibility to use both enantiomers of epichlorohydrin and the diastereodivergency found in the reduction process paves the way for a general preparation also in the nonracemic form of chiral trans- fused 3-substituted octahydrobenzo[ g ]quinolines that are privileged structures in medicinal chemistry.