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

2010-01-01T00:00:00Z (GMT) by Soyeong Kang Hyeon-Kyu Lee
A highly efficient, enantioselective sequence has been developed for the synthesis of (<i>S</i>)- and (<i>R</i>)-dapoxetine. The pathways involve the intermediacy of the 6-membered-ring sulfamate esters <b>4</b>, which were generated by Du Bois asymmetric C−H amination reactions of the prochiral sulfamate <b>3</b>, 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 (<b>4r</b>), prepared by the Du Bois asymmetric C−H amination reaction of <b>3</b> and the Rh<sub>2</sub>(<i>S</i>-nap)<sub>4</sub> catalyst, is determined to be <i>R</i> and not <i>S</i> as was originally reported.