Subscribe to RSS
Download PDF
DOI: 10.1055/a-2711-1520
Facile Preparation of Chiral 1,2-Amino Alcohols Containing Unsymmetrical N-α-Secondary Alkyl Substituents
Authors
Supported by: National Natural Science Foundation of China 22271182
Funding Information The authors acknowledge the financial support of the National Natural Science Foundation of China (22271182).
Abstract
To address the lack of general synthetic methods for accessing chiral 1,2-amino alcohols bearing unsymmetrical N-α-secondary-alkyl groups (CAUAs), we developed an efficient protocol based on diastereoselective addition of alkyl Grignard and MeLi reagents to (S)-3,3-dimethyl-1,7a-dihydro-3H,5H-pyrrolo [1,2-c]oxazol-5-one (2). Careful methanolysis of the resulting adducts provided diverse CAUAs featuring a terminal ester functionality. Notably, intermediate 11 served as a key precursor for the synthesis of BiOx ligand 12, which exhibited exceptional performance in catalyzing the Ni-catalyzed enantioselective coupling of α-iodoacetals with aryl bromides.
Publication History
Received: 27 July 2025
Accepted after revision: 26 September 2025
Accepted Manuscript online:
26 September 2025
Article published online:
07 November 2025
© 2025. Thieme. All rights reserved.
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1a Ager DJ, Prakash I, Schaad DR. Chem Rev 1996; 96: 835
- 1b Gupta P, Mahajan N. New J Chem 2018; 42: 12296
- 1c Caner J, Matsumoto A, Maruoka K. Chem Sci 2023; 14: 13879
- 1d Lee HS, Kang SH. Synlett 2004; 10: 1673
- 2 Huo H, Gorsline BJ, Fu GC. Science 2020; 367: 559
- 3a Poremba KE, Dibrell SE, Reisman SE. ACS Catal 2020; 10: 8237
- 3b Cherney AH, Kadunce NT, Reisman SE. J Am Chem Soc 2013; 135: 7442
- 4a Tu H-Y, Wang F, Huo L. et al. J Am Chem Soc 2020; 142: 9604
- 4b García-Domínguez A, Li Z, Nevado C. J Am Chem Soc 2017; 139: 6835
- 5 Janssen-Müller D, Sahoo B, Sun S-Z, Martin R. Isr J Chem 2020; 60: 195
- 6a Cheng X, Li T, Liu Y, Lu Z. ACS Catal 2021; 11: 11059
- 6b Cheng X, Lu H, Lu Z. Nat Commun 2019; 10: 3549
- 6c Shu X, Huan L, Huang Q, Huo H. J Am Chem Soc 2020; 142: 19058
- 7a Burk MJ, Gross MF, Martinez JP. J Am Chem Soc 1995; 117: 9375
- 7b Gridnev ID, Imamoto T, Hoge G, Kouchi M, Takahashi H. J Am Chem Soc 2008; 130: 2560
- 8a Ni S, Garrido-Castro AF, Merchant RR. et al. Angew Chem Int Ed 2018; 57: 14560
- 8b Shatskiy A, Axelsson A, Stepanova EV. et al. Chem Sci 2021; 12: 5430
- 9 Qi R, Wang C, Huo Y. et al. J Am Chem Soc 2021; 143: 12777
- 10 So RC, Ndonye R, Izmirian DP, Richardson SK, Guerrera RL, Howell AR. J Org Chem 2004; 69: 3233
- 11a Poremba KE, Kadunce NT, Suzuki N, Cherney AH, Reisman SE. J Am Chem Soc 2017; 139: 5684
- 11b Woods BP, Orlandi M, Huang C-Y, Sigman MS, Doyle AG. J Am Chem Soc 2017; 139: 5688
- 11c He Y, Liu C, Yu L, Zhu S. Angew Chem Int Ed 2020; 59: 21530
- 12 Huang G, Wu Y, Gong H, Chen Y. Org Biomol Chem 2023; 21: 6111
- 13a Guo L, Yuan M. et al. J Am Chem Soc 2020; 142: 20390
- 13b Wei X, Shu W, García-Domínguez A, Merino E, Nevado C. J Am Chem Soc 2020; 142: 13515
- 14a Yang C, Liu Z-L. et al. Org Lett 2020; 22: 1360
- 14b Tenberge M, Wahl JM. Synthesis 2023; 55: 892
- 15a Wang Y-Z, Sun B. et al. J Am Chem Soc 2023; 145: 23910
- 15b Yang T, Xiong W, Sun G, Yang W, Lu M, Koh MJ. J Am Chem Soc 2024; 146: 29177
- 15c Cao P, Xiong W, Yang T. Org Lett 2025; 27: 1475
- 15d Zhou P, Li X, Wang D, Xu T. Org Lett 2021; 23: 4683
- 16a Kranidiotis-Hisatomi N, Yi H, Oestreich M. Angew Chem Int Ed 2021; 60: 13652
- 16b Zhou J, Fu GC. J Am Chem Soc 2003; 125: 14726
- 16c Chen F, Zhang Q, Li Y, Yu Z-X, Chu L. J Am Chem Soc 2024; 146: 11418
- 17a Davies SG, Dixon DJ, Doisneau GJ-M, Prodger JC, Sanganee HJ. Tetrahedron-Asymmetry 2002; 13: 647
- 17b Mainolfi N, Ji N, Weiss MW, Zheng X, Zhang Y, Fleming PR. WO2020/264490 A1 2020
- 18 Wright SW, Choi C, Chung S. et al. Org Lett 2015; 17: 5204
- 19 Mon M, Bruno R, Elliani R. et al. Inorg Chem 2018; 57: 13895
- 20 Woods BP, Orlandi M, Huang CY, Sigman MS, Doyle AGJ. Chem Soc Chem 2017; 139: 5688
- 21a Nagasaka T, Imai T. Chem Pharm Bull 1995; 43: 1081
- 21b Guo S, Wang J, Yao S. et al. WO 2020/259668 A1 2020
- 22 Lindgren AEG, Karlberg T, Ekblad T. et al. J Med Chem 2013; 56: 9556
- 23 See the Supporting Information for details
- 24 Qiu C, Liu L, Zhang K. et al. J Am Chem Soc 2025; 147: 17251
For selected references on S-Bu Biox, see:
For selected references on Box, see:
For selected references on Bilm, see:
For selected references on Pybox, see: