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

abstract

  • 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%).

author list (cited authors)

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

publication date

  • January 1, 2018 11:11 AM