Synthesis of a Sitagliptin Intermediate via Ruthenium-Catalyzed Asymmetric Hydrogenation of Enamine Ester

doi:10.6023/cjoc202408013

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钌催化烯胺酯的不对称氢化合成西格列汀手性中间体

吕逸文^a, 廖海华^a, 汤文军^a,b,c,*

^a华东理工大学药学院上海 200237;
^b中国科学院上海有机化学研究所生命过程小分子调控全国重点实验室上海 200032;
^c国科大杭州高等研究院化学和材料科学学院杭州 310024

收稿日期:2024-08-08 修回日期:2024-08-31
基金资助:
国家重点研发计划（2022YFA1503702, 2021YFF0701601）,国家自然科学基金(No. 82188101 )资助项目.

Synthesis of a Sitagliptin Intermediate via Ruthenium-Catalyzed Asymmetric Hydrogenation of Enamine Ester

Lv Yiwen^a, Liao Haihua^a, Tang Wenjun^a,b,c,*

^aEast China University of Science and Technology, School of Pharmacy, Shanghai, 200237;
^bState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032;
^cSchool of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024

Received:2024-08-08 Revised:2024-08-31
Contact: *E-mail: tangwenjun@sioc.ac.cn.
Supported by:
National Key R&D Program of China (2022YFA1503702, 2021YFF0701601), NSFC (82188101).

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Abstract

This paper aims at developing a highly enantioselective ruthenium-catalyzed asymmetric hydrogenation of enamine ester to synthesize the chiral intermediate of sitagliptin. Through a comprehensive investigation of ruthenium catalyst precursors, chiral ligands, acids and ammonium salts as additives, temperature, pressure, and solvent, (R)-3-amino-4-(2,4,5- trifluorophenyl) isopropyl butyrate, the key intermediate of sitagliptin, was obtained in 97% yield and 99% ee by asymmetric hydrogenation from β-2,4,5-trifluorophenyl-β-enamine ester under the action of Ru-BIBOP catalyst, with p-toluenesulfonic acid and ammonium p-toluenesulfonate as additives, and dichloromethane/methanol as solvent, under 50 atm of hydrogen pressure and 60 ℃ for 22 hours. The use of Ru-BIBOP catalyst plays a key role in achieving high enantioselectivity for this transformation.

Key words: ruthnium, enamide easter, asymmetric hydrogenation, Sitagliptin

Cite this article

Lv Yiwen, Liao Haihua, Tang Wenjun. Synthesis of a Sitagliptin Intermediate via Ruthenium-Catalyzed Asymmetric Hydrogenation of Enamine Ester[J]. Chinese Journal of Organic Chemistry, doi: 10.6023/cjoc202408013.

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[1]Kim D.; Wang L.; Beconi M.; Eiermann G. J.; Fisher M. H.; He H.; Hickey G. J.; Kowalchick J. E.; Leiting B.; Lyons K.; Marsilio F.; McCann M. E.; Patel R. A.; Petrov A.; Scapin G.; Patel S. B.; Roy R. S.; Wu J. K.; Wyvratt M. J.; Zhang B. B.; Zhu L.; Thornberry N. A.; Weber, A. E. J. Med. Chem.2005, 48, 141-151.
[2]Hansen K. B.; Balsells J.; Dreher S.; Hsiao Y.; Kubryk M.; Palucki M.; Rivera N.; Steinhuebel D.; Armstrong J. D.; Askin D.; Grabowski, E. J. J. Org. Process Res. Dev.2005, 9, 634-639.
[3]Hansen K. B.; Hsiao Y.; Xu F.; Rivera N.; Clausen A.; Kubryk M.; Krska S.; Rosner T.; Simmons B.; Balsells J.; Ikemoto N.; Sun Y.; Spindler F.; Malan C.; Grabowski E. J. J.; Armstrong, J. D. J. Am. Chem. Soc.2009, 131, 8798-8804.
[4]Wu, S.; Yu, B.; Wang, Y.; Zhu, [J].CN 102271504 B, 2014.
[5]Steinhuebel D.; Sun Y.; Matsumura K.; Sayo N.; Saito, T. J. Am. Chem. Soc.2009, 131, 11316-11317.
[6]Savile C. K.; Janey J. M.; Mundorff E. C.; Moore J. C.; Tam S.; Jarvis W. R.; Colbeck J. C.; Krebber A.; Fleitz F. J.; Brands J.; Devine P. N.; Huisman G. W.; Hughes G. J. Science2010, 329, 305-309.
[7]MacNeil C. S.; Zhong H.; Pabst T. P.; Shevlin M.; Chirik, P. J. ACS Catal.2022, 12, 4680-4687.
[8] a) Yan, Z.; Sun, B.; Huang, P.; Zhao, H.; Ding, H.; Su, W.; Jin, C. Chin. Chem. Lett. 2022, 33, 1997-2000.
b) Zhang, Z.; Butt, N. A.; Zhang, W.Chem. Rev. 2016, 116, 14769-14827.
c) Song, H.; Li, Y.; Yao, Q. J.; Jin, L.; Liu, L.; Liu, Y. H.; Shi, B. F. Angew. Chem. Int. Ed. 2020, 59, 6576-6580.
[9]Nugent T. C.; El‐Shazly M.2010, 352, 753-819.
[10]a) Blaser, H.-U.; Buser, H.-P.; Coers, K.; Hanreich, R.; Jalett, H.-P.; Jelsch, E.; Pugin, B.; Schneider, H.-D.; Spindler, F.; Wegmann, A.Chimia 1999, 53, 275-280.
b) Hou C.; Wang Y.; Zheng Z.; Xu J.; Hu, X. Org. Lett. 2012, 14,3554-3557;
c) Li, Q.; Hou, C.-J.; Liu, X.-N.; Huang, D.-Z.; Liu, Y.-J.; Yang, R.-F.; Hu, X.-P.RSC Advances 2015, 5, 13702-13708.
d) Li, C.; Wan, F.; Chen, Y.; Peng, H.; Tang, W.; Yu, S.; McWilliams, J. C.; Mustakis, J.; Samp, L.; Maguire, R. J. Angew. Chem. Int. Ed. 2019, 58, 13573-13583.
[11]Xie J.-H.; Zhu S.-F.; Zhou Q.-L. Chem. Rev.2011, 111, 1713-1760.
[12]a) Xu G.; Senanayake C. H.; Tang, W. Acc. Chem. Res.2019, 52, 1101-1112.
b) Cao Z.; He D.; Tang, W. Org. Process Res. Dev.2024, 28, 949-977.
[13]Tang, W.; Qu, B.; Capacci, A. G.; Rodriguez, S.;0 Wei, X.; Haddad, N.; Narayanan, B.; Ma, S.; Grinberg, N.; Yee, N. K.; Krishnamurthy, D.; Senanayake, C. H.Org. Lett. 2010, 12, 172-179.
[14]Li, W.; Rodriguez, S.; Duran, A.; Sun, X.; Tang, W.; Premasiri, A.; Wang, J.; Sidhu, K.; Patel, N. D.; Savoie, J.; Qu, B.; Lee, H.; Haddad, N.; Lorenz, J. C.; Nummy, L.; Hossain, A.; Yee, N.; Lu, B.; Senanayake, C. H.Org. Process Res. Dev. 2013, 17, 1061-1065.
[15]Luo, R.; Li, K.; Tang, W.Adv. Syn. Cat. 2013, 355, 1297-1302.
[16]Liu G.; Liu X.; Cai Z.; Jiao G.; Xu G.; Tang, W. Angew. Chem., Int. Ed.2013, 52, 4235-4238.
[17]Clausen A. M.; Dziadul B.; Cappuccio K. L.; Kaba M.; Starbuck C.; Hsiao Y.; Dowling, T. M. Org. Process Res. Dev.2006, 10, 723-726.

钌催化烯胺酯的不对称氢化合成西格列汀手性中间体

Synthesis of a Sitagliptin Intermediate via Ruthenium-Catalyzed Asymmetric Hydrogenation of Enamine Ester

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