An efficient enantioselective synthesis of the D1 agonist (5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopenta[c] phenanthrene-9,10-diol (A-86929)

(5aR,11bS)-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-azacyclopenta[c]phenanthrene-9,10-diol (A-86929, 1), a potent selective dopamine D1 agonist, was synthesized enantioselectively from D-aspartic acid. Key features of the 10-step synthesis are the following: (1) there is no chromatography required; (2) formation of 15 occurs in >99% ee; (3) the electrophilic cyclization to provide the desired trans stereochemisty in 18 is achieved with no loss of enantiomeric integrity.