Synlett 2020; 31(02): 171-174
DOI: 10.1055/s-0039-1691406
letter
© Georg Thieme Verlag Stuttgart · New York

A Convenient One-Pot Synthesis of Both Enantiomers of 1,3,5-Trisubstituted Hydantoins

Gun Hee Han
,
Seo Yun Kim
,
Ha Rim Lee
,
Ji Su Lee
,
Yong Sun Park
Department of Chemistry, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea   Email: parkyong@konkuk.ac.kr
› Author Affiliations
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)


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.

Supporting Information

 
  • References and Notes

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  • 8 1,3,5-Trisubstituted Hydantoins 310: 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 1ad 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.