Multicomponent Synthesis of N-Carbamoyl Hydantoin Derivatives

Maria Cristina Bellucci; Massimo Frigerio; Tommaso Marcelli; Alessandro Volonterio

doi:10.1055/s-0032-1318432

Synlett, Table of Contents

Synlett 2013; 24(6): 727-732
DOI: 10.1055/s-0032-1318432

letter

Multicomponent Synthesis of N-Carbamoyl Hydantoin Derivatives

Maria Cristina Bellucci

^aDepartment of Food, Environmental and Nutritional Sciences, Università degli Studi di Milano, Via Celoria 2, 20133 Milano, Italy

,

Massimo Frigerio

^bDepartment of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy Fax: +39(02)23993180 Email: alessandro.volonterio@polimi.it

,

Tommaso Marcelli

^bDepartment of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy Fax: +39(02)23993180 Email: alessandro.volonterio@polimi.it

,

Alessandro Volonterio*

^bDepartment of Chemistry, Materials, and Chemical Engineer ‘Giulio Natta’, Politecnico di Milano, Via Mancinelli 7, 20131 Milano, Italy Fax: +39(02)23993180 Email: alessandro.volonterio@polimi.it

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Abstract

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Abstract

A novel, three-component process for the preparation of a small library of unprecedented nonracemic N-carbamoyl hydantoins under very mild conditions, as well as the hypothetic mechanism, are presented.

Key words

domino reaction - multicomponent reaction - heterocycles - hydantoins - Staudinger reaction

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References

References and Notes

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7 Characterization of Compound 4a R_f = 0.43 (hexane–EtOAc, 60:40); [a]_D ²⁰ +33.3 (c 1.0, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 8.17 (t, J = 5.6 Hz, 1 H), 7.38–6.97 (m, 15 H), 4.83 (dd, J = 5.6, 2.4 Hz, 1 H), 4.62 (dd, J = 14.8, 6.0 Hz, 1 H), 4.52 (d, J = 14.8 Hz, 1 H), 4.50 (dd, J = 14.8, 6.8 Hz, 1 H), 3.70 (dd, J = 14.0, 5.6 Hz, 1 H), 3.30 (dd, J = 14.0, 2.4 Hz, 1 H). ¹³C NMR (125.7 MHz, CDCl₃): δ = 170.5, 155.3, 151.1, 138.0, 133.3, 129.7, 128.7, 128.6, 128.5, 128.2, 128.0, 127.6, 127.4, 59.9, 43.9, 42.4, 34.9. ESI-MS: m/z (%) = 259.1 (100), 436.2 (38) [M⁺ + H]. Anal. Calcd for C₂₅H₂₃N₃O₃: C, 72.62, H, 5.61, N, 10.16. Found: C, 72.67, H, 5.64, N, 10.11.
8 Zhang D, Xing X, Cuny GD. J. Org. Chem. 2006; 71: 1750
9 The ee was determined by chiral HPLC (see Supporting Information). In this regard, we would like to acknowledge the referee who suggested we check the ee of the N-carbamoyl hydantoins obtained by our process
10 The starting α-azido esters 1 were prepared from the corresponding α-amino esters by diazotransfer reaction promoted by imidazole-1-sulfonyl azide hydrochloride: Goddard-Borger ED, Stick RV. Org. Lett. 2007; 9: 3797
11 General Procedure for the Preparation of N-Carbamoyl Hydantoins 4 To a stirred solution of α-azido ester 1 (1equiv) and isocyanate 2 (2.5 equiv) in MeCN (0.1 M solution), solid Ph₃P (1equiv) was added and the solution stirred at r.t. for 3 h. The solvent was removed under reduced pressure and the crude purified by flash chromatography.
12 Since both N-carbamoyl hydantoins 4a and 4i have ca. 60% ee, we assume that also N-carbamoyl hydantoins 4b–f,k–l posses the same ee since the process was run under the same conditions, i.e., in MeCN at r.t. for 3 h

Supplementary Material

Supporting Information