Development of a Scalable, Chromatography-Free Synthesis of t-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF3-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation. Academic Article uri icon


  • A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).

published proceedings

  • J Org Chem

altmetric score

  • 0.75

author list (cited authors)

  • Sieber, J. D., Rodriguez, S., Frutos, R., Buono, F., Zhang, Y., Li, N., ... Senanayake, C. H.

citation count

  • 10

complete list of authors

  • Sieber, Joshua D||Rodriguez, Sonia||Frutos, Rogelio||Buono, Frederic||Zhang, Yongda||Li, Ning||Qu, Bo||Premasiri, Ajith||Li, Zhibin||Han, Zhengxu S||Xu, Yibo||Byrne, Denis||Haddad, Nizar||Lorenz, Jon||Grinberg, Nelu||Kurouski, Dmitry||Lee, Heewon||Narayanan, Bikshandarkoil||Nummy, Laurence||Mulder, Jason||Brown, Jack D||Granger, Alice||Gao, Joe||Krawiec, Mariusz||Williams, Zeena||Pennino, Scott||Song, Jinhua J||Hossain, Azad||Yee, Nathan K||Busacca, Carl||Roschangar, Frank||Xin, Yanchao||Mao, Zhantong||Zhang, Xinzhu||Hong, Yaping||Senanayake, Chris H

publication date

  • February 2018