Stereoselective C9 Arylation and Vinylation of <i>Cinchona</i> Alkaloids

A simple and efficient method for the highly stereoselective C-9 arylation and vinylation of Cinchona alkaloids was developed. Both 9S- and 9R-chloroquinine with PhMgBr yielded 9S-phenylquinine (X-ray structure). The reactions with various aryl and vinyl Grignard reagents resulted in the series of 9S-aryl and vinyl alkaloid derivatives. The stereochemical outcome was rationalized by coordination of the magnesium atom to the quinuclidine nitrogen, thus directing the nucleophilic attack at the C-9 stereogenic center.