THE ENANTIOSELECTIVE SYNTHESIS OF THE POTENT DOPAMINE D1 AGONIST (1R,3S)-3-(1'-ADAMANTYL)-1-(AMINOMETHYL)-3,4-DIHYDRO-5,6-DIHYDROXY-1H-2-BENZOPYRAN (A77636)

The synthesis of both enantiomers of the title compound is described. The corresponding racemic compound (+/-)-1 was previously shown to be a highly potent and selective dopamine Dl agonist. Key to the synthesis of the enantiomers was the oxazaborolidine-catalyzed asymmetric reduction of the alpha-bromomethyl ketone 12 which led to the optically enriched epoxide 7. An aryllithium addition to the epoxide followed by a diastereospecific cyclization to the isochroman system furnished compound 17, which was deprotected to afford (-)-1 with >99.5% optical purity.