Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2020; 31(02): 171-174
DOI: 10.1055/s-0039-1691406
DOI: 10.1055/s-0039-1691406
letter
A Convenient One-Pot Synthesis of Both Enantiomers of 1,3,5-Trisubstituted Hydantoins
Konkuk University (grant/award number: 2018)Further Information
Publication History
Received: 31 October 2019
Accepted after revision: 25 November 2019
Publication Date:
04 December 2019 (online)
![](https://www.thieme-connect.de/media/synlett/202002/lookinside/thumbnails/st-2019-d0591-l_10-1055_s-0039-1691406-1.jpg)
Abstract
A novel one-pot asymmetric synthetic method for the direct conversion of bromoacetates into highly substituted hydantoins has been developed. Both enantiomers of 1,3,5-trisubstituted hydantoins were conveniently synthesized through a dynamic kinetic resolution of bromoacetates derived from either ethyl l-lactate or diacetone-d-glucose. The sequential three-component reaction permitted the preparation of (R)- or (S)-1,3,5-trisubstituted hydantoins in yields of 77–51% with enantiomeric ratios of up to 95:5.
Key words
hydantoins - one-pot reaction - asymmetric synthesis - kinetic resolution - chiral auxiliaries - bromoacetatesSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691406.
- Supporting Information
-
References and Notes
- 1a Konnert L, Lamaty F, Martinez J, Colacino E. Chem. Rev. 2017; 117: 13757
- 1b Cho S, Kim S.-H, Shin D. Eur. J. Med. Chem. 2019; 164: 517
- 1c Meusel M, Gütschow M. Org. Prep. Proced. Int. 2004; 36: 391
- 2a Declas N, Le Vaillant F, Waser J. Org. Lett. 2019; 21: 524
- 2b Liu H, Yang Z, Pan Z. Org. Lett. 2014; 16: 5902
- 2c Zhang D, Xing X, Cuny GD. J. Org. Chem. 2006; 71: 1750
- 2d Zhang W, Lu Y. Org. Lett. 2003; 5: 2555
- 3a Song J, Zhang Z.-J, Chen S.-S, Fan T, Gong L.-Z. J. Am. Chem. Soc. 2018; 140: 3177
- 3b Ma B.-D, Du S.-H, Wang Y, Ou X.-M, Huang M.-Z, Wang L.-X, Wang X.-G. Tetrahedron: Asymmetry 2017; 28: 47
- 3c Kotha S, Gupta NK, Aswar VR. Chem. Asian J. 2019; 14: 3188
- 4a Barnwell N, Watts A, Purdie L, Gill DM. Tetrahedron Lett. 2012; 53: 1951
- 4b Atkinson RC, Fernández-Nieto F, Roselló JR, Clayden J. Angew. Chem. Int. Ed. 2015; 54: 8961
- 4c Kondoh A, Ota Y, Komuro T, Egawa F, Kanomata K, Terada M. Chem. Sci. 2016; 7: 1057
- 4d Mas-Roselló J, Okoh M, Clayden J. Chem. Commun. 2018; 54: 10985
- 4e Izquierdo J, Etxabe J, Duñabeitia E, Landa A, Oiarbide M, Palomo C. Chem. Eur. J. 2018; 24: 7217
- 4f Tomohara K, Yoshimura T, Hyakutake R, Yang P, Kawabata T. J. Am. Chem. Soc. 2013; 135: 13294
- 4g Saunthwal RK, Cornall MT, Abrams R, Ward JW, Clayden J. Chem. Sci. 2019; 10: 3408
- 5a Park YS. Tetrahedron: Asymmetry 2009; 20: 2421
- 5b Kim Y, Park KJ, Choi YS, Lee M, Park YS. Bull. Korean Chem. Soc. 2013; 34: 2531
- 5c Ammazzalorso A, Amoroso R, Bettoni G, De Filippis B, Fantacuzzi M, Giampietro L, Maccallini C, Tricca ML. Eur. J. Org. Chem. 2006; 4088
- 6a Kim HJ, Shin E.-k, Chang J.-y, Kim Y, Park YS. Tetrahedron Lett. 2005; 46: 4115
- 6b Kim HJ, Kim Y, Choi ET, Lee MH, No ES, Park YS. Tetrahedron 2006; 62: 6303
- 6c Kim Y, Lee MH, Choi ET, No ES, Park YS. Heterocycles 2007; 71: 5
- 7 Hayashi Y. Chem. Sci. 2016; 7: 866
- 8 1,3,5-Trisubstituted Hydantoins 3–10: General Procedure The appropriate amine (1.0 equiv) and TBAI (1.0 equiv) were added to a stirred solution of a 1:1 diastereomeric mixture of bromoacetate 1a–d in CH2Cl2 at r.t. After the disappearance of 1 (TLC; 15–20 h), the appropriate isocyanate (1.2 equiv) and pyridine (1.2 equiv) were added, and the mixture was allowed to stand at r.t. for 0.5–1 h. The resulting mixture was washed with sat. aq NH4Cl, dried (MgSO4), filtered, concentrated, and purified by column chromatography. 1-Benzyl-3,5-diphenylhydantoin (4) Colorless oil; yield: yield: 109 mg (64%, R/S er 93:7) from 1a; 111 mg (64%, S/R er 92:8) from 1c. HPLC (Chiralpak AD-H; 40% i-PrOH–hexane, 0.5 mL/min): t R (R)-4: 24.0 min; t R (S)-4: 33.9 min. 1H NMR (CDCl3, 400 MHz): δ = 7.47–7.18 (m, 15 H), 5.24 (d, J = 15.2 Hz, 1 H), 4.82 (s, 1 H), 3.81 (d, J = 15.2 Hz, 1 H). 13C NMR (CDCl3, 100 MHz): δ = 170.1, 155.5, 135.2, 132.5, 131.8, 129.5, 129.4, 129.1, 129.0, 128.7, 128.3, 128.2, 127.7, 126.1, 62.9, 44.8. HRMS: m/z [M + H]+ Calcd for C22H19N2O2: 343.1447; found: 343.1445.
For examples of asymmetric synthesis of 5,5-disubstituted hydantoins, see: