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Synlett 2009(13): 2109-2114  
DOI: 10.1055/s-0029-1217567
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Trapping of an Ammonium Ylide with Activated Ketones: Synthesis of β-Hydroxy-α-Amino Esters with Adjacent Quaternary Stereocenters

Xin Guo, Yongli Yue, Guoliang Hu, Jing Zhou, Yiqing Zhao, Liping Yang, Wenhao Hu*
Department of Chemistry, East China Normal University, Shanghai 200062, P. R. of China
Fax: +86(21)62233176; e-Mail: whu@chem.ecnu.edu.cn;
Further Information

Publication History

Received 31 March 2009
Publication Date:
15 July 2009 (online)

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Abstract

A novel Rh2(OAc)4-catalyzed three-component reaction of diazoacetates, anilines, and activated ketones via ammonium ylide trapping processes is reported. The reaction of isatins afforded α-amino-β-hydroxy esters bearing the 3-substituted 3-hydroxyindolin-2-one moiety with vicinal quaternary carbon centers in one step with high chemo- and diastereoselectivity. Extension of the reaction to acyclic α-keto esters afforded 2-hydroxy-2-alkyl-3-aryl-3-(phenylamino) succinates in moderate yield and diastereoselectivity.

Key words

rhodium - ylides - multicomponent reactions - amino alcohol - ketones

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General Procedure: To a refluxing CH2Cl2 (5 mL) solution of Rh2(OAc)4 (2.25 mg, 1 mol%), anilines 2 (0.60 mmol), and 3 or 6 (0.50 mmol) under argon atmosphere was added diazoacetates 1 (0.60 mmol) in CH2Cl2 (2 mL) over 2 h via a syringe pump. After the addition was completed, the reaction mixture was cooled to r.t. Solvent was removed, and the crude product was purified by flash column chromatog-raphy on silica gel eluting with EtOAc-PE to give 4 and 5 or 7 and 8.
Compound 4l: 50% yield. ¹H NMR (500 MHz, CDCl3-TMS): δ = 7.53-7.52 (d, J = 7.5 Hz, 1 H), 7.40-7.12 (m, 5 H), 6.86-6.78 (m, 4 H), 5.00 (d, J = 11.4 Hz, 1 H), 4.58 (d, J = 11.4 Hz, 1 H), 4.10 (s, 1 H), 3.99-3.94 (m, 2 H), 3.17 (s, 3 H), 0.98v0.95 (t, J = 7.0 Hz, 3 H). ¹³C NMR (125 MHz, CDCl3-TMS): δ = 175.7, 170.3, 146.0, 144.2, 130.6, 129.2, 126.2, 125.0, 123.1, 119.8, 115.0, 108.5, 74.72, 63.2, 61.3, 26.1, 13.5. ESI-HRMS: m/z calcd for C19H20N2NaO4 [M + Na]+: 363.1315; found: 363.1321.

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Crystal Data for erythro -4a: C24H22N2O4, M w = 420.44, orthorhombic, space group Pbca, a = 8.9039 (9) Å, b = 15.0755 (15) Å, c = 31.070 (3) Å, V = 4170.5 (7) ų, Z = 8, ρ calcd = 1.282 mg/m³, F(000) = 1696, λ = 0.71073 Å, T = 293 (2) K, µ(MoKα) = 0.08 mm-¹. Data for the structure were collected on a Siemens P-4X four-circle diffracto-meter. Intensity measurements were performed on a crystal (dimensions 0.48 × 0.44 × 0.40 mm). In the range 2.62 < 2θ < 52.04, of the 16851 measured reflections, 4087 were independent (Rint = 0.0817). The structures were solved by direct methods (SHELXS-97) and refined by full-matrix least-squares on F ². The final refinements converged at R 1 = 0.0512 for I > 2σ(I), and wR 2 = 0.1104 for all data. The final difference Fourier synthesis gave a min/max residual electron density of -0.200/-0.166 e Å-³. CCDC-716407 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www. ccdc.cam.ac.uk [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK, fax +44 (1223)762910, or deposit@ccdc.cam.ac.uk].

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Crystal Data for erythro -7a: C19H21NO5, M w = 343.37, monoclinic, space group P2 (1)/c, a = 14.293 (2) Å, b = 6.574 (1) Å, c = 19.822 (3) Å, β = 108.19 (1), V = 1769.4 (5) ų, Z = 4, ρ calcd = 1.289 mg/m³, F(000) = 728, λ = 0.71073 Å, T = 296 (2) K, µ(MoKα) = 0.096 mm-¹. Data for the structure were collected on a Siemens P-4X four-circle diffractometer. Intensity measurements were performed on a crystal (dimensions 0.62 × 0.56 × 0.48mm). In the range 3 < 2θ < 54, Of the 4773 measured reflections, 3875 were inde-pendent (R int = 0.0138). The structure was solved by direct methods (SHELXS-97) and refined by full-matrix least-squares on F ². The final refinements converged at R1 = 0.0399 for I > 2σ(I), wR 2 = 0.0979 for all data. The final difference Fourier synthesis gave a min/max residual electron density of -0.177/+0.19 e Å-³. CCDC-686324 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www. ccdc.cam.ac.uk [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge CB2 1EZ, UK, fax +44 (1223)762910, or deposit@ccdc.cam.ac.uk].