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
| Autor: | Yanchao Xin, Frank Roschangar, Zeena Williams, Denis Byrne, Dmitry Kurouski, Jason A. Mulder, Jinhua J. Song, Alice T. Granger, Laurence J. Nummy, Jon C. Lorenz, Scott Pennino, Frederic G. Buono, Chris H. Senanayake, Yaping Hong, Ajith Premasiri, Nathan K. Yee, Joe Gao, Sonia Rodriguez, Xinzhu Zhang, Bo Qu, Jack D. Brown, Rogelio P. Frutos, Bikshandarkoil A. Narayanan, Zhantong Mao, Azad Hossain, Ning Li, Mariusz Krawiec, Heewon Lee, Yongda Zhang, Zhengxu S. Han, Nizar Haddad, Zhibin Li, Yibo Xu, Nelu Grinberg, Joshua D. Sieber, Carl A. Busacca |
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| Rok vydání: | 2018 |
| Předmět: |
Chiral auxiliary
Trifluoromethyl Chromatography 010405 organic chemistry Ligand Organic Chemistry Asymmetric hydrogenation Enantioselective synthesis 010402 general chemistry 01 natural sciences 0104 chemical sciences chemistry.chemical_compound chemistry Yield (chemistry) Vinyl acetate Enantiomeric excess |
| Zdroj: | The Journal of Organic Chemistry. 83:1448-1461 |
| ISSN: | 1520-6904 0022-3263 |
| Popis: | 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%). |
| Databáze: | OpenAIRE |
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