Enantioselective Synthesis of (R)-Sitagliptin via Phase-Transfer Catalytic aza-Michael Additionopen access
- Authors
- Oh, Daehyun; Lee, Jaeyong; Yang, Sehun; Jung, So Hyun; Kim, Mihyun; Lee, Geumwoo; Park, Hyeung-Geun
- Issue Date
- Mar-2024
- Publisher
- American Chemical Society
- Citation
- ACS Omega, v.9, no.13, pp 15328 - 15338
- Pages
- 11
- Journal Title
- ACS Omega
- Volume
- 9
- Number
- 13
- Start Page
- 15328
- End Page
- 15338
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/91045
- DOI
- 10.1021/acsomega.3c10080
- ISSN
- 2470-1343
2470-1343
- Abstract
- The highly enantioselective synthesis of (R)-sitagliptin has been achieved through a series of key steps, including the aza-Michael addition and Baeyer-Villiger oxidation. The enantioselective aza-Michael addition involved the reaction of tert-butyl β-naphthylmethoxycarbamate with (E)-1-(4-methoxyphenyl)-4-(2,4,5-trifluorophenyl)but-2-en-1-one, utilizing a quinine-derived C(9)-urea ammonium catalyst under phase-transfer catalytic conditions. The aza-Michael addition successfully introduced chirality to the amine in (R)-sitagliptin with 96% ee. The subsequent Baeyer-Villiger oxidation of the aza-Michael adduct led to the formation of 4-methoxyphenyl ester. Hydrolysis and amide coupling were then employed to construct the amide moiety. Further deprotections were performed to complete the synthesis of (R)-sitagliptin (7 steps, 41%, 96% ee). © 2024 The Authors. Published by American Chemical Society
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