Highly Efficient, Enantioselective Syntheses of (S)-(+)- and (R)-(-)-Dapoxetine Starting with 3-Phenyl-1-propanol

A highly efficient, enantioselective sequence has been developed for the synthesis of (S)- and (R)-dapoxetine. The pathways involve the intermediacy of the 6-membered-ring sulfamate esters 4, which were generated by Du Bois asymmetric C-H amination reactions of the prochiral sulfamate 3, catalyzed by the chiral dirhodium(II) complexes. During the Course of our research, the absolute configuration of the enantiomer of 4-pheny[1,2,3]oxathiazinane 2,2-dioxide (4r), prepared by the Du Bois asymmetric C-H amination reaction of 3 and the Rh-2(S-naP)(4) catalyst, is determined to be R and not S as wits originally reported.