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1 Enantioselective Synthesis of 3,3-Dihydropyrryl-spirooxindoles via an Organocatalytic Three-Component Reaction Wen-Tao Wei, Chun-Xia Chen, Rui-Jiong Lu, Jin-Jia Wang, Xue-Jing Zhang, Ming Yan* Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China SUPPORTING INFORMATION INDEX A) GENERAL INFORMATION........................................................................................... 2 B) GENERAL PROCEDURE FOR THE CONJUGATE ADDITION................................. 2 C) PREPARATION OF RACEMIC SAMPLES ................................................................... 2 D) X-RAY CRYSTAL STRUCTURE INFORMATION. ..................................................... 3 E) REFERENCES ................................................................................................................. 3 F) NMR SPECTRA OF PRODUCTS ................................................................................... 4 G) HPLC CHROMATOGRAMS OF PRODUCTS ............................................................ 25 Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012

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  • 1

    Enantioselective Synthesis of 3,3′-Dihydropyrryl-spirooxindoles via

    an Organocatalytic Three-Component Reaction

    Wen-Tao Wei, Chun-Xia Chen, Rui-Jiong Lu, Jin-Jia Wang, Xue-Jing Zhang, Ming Yan*

    Institute of Drug Synthesis and Pharmaceutical Process, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China

    SUPPORTING INFORMATION

    INDEX

    A) GENERAL INFORMATION ........................................................................................... 2

    B) GENERAL PROCEDURE FOR THE CONJUGATE ADDITION ................................. 2

    C) PREPARATION OF RACEMIC SAMPLES ................................................................... 2

    D) X-RAY CRYSTAL STRUCTURE INFORMATION. ..................................................... 3

    E) REFERENCES ................................................................................................................. 3

    F) NMR SPECTRA OF PRODUCTS ................................................................................... 4

    G) HPLC CHROMATOGRAMS OF PRODUCTS ............................................................ 25

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    A) General Information Experimental Methods 1H NMR and 13C NMR spectra were recorded on Bruker AVANCE 400 spectrometer. Chemical shifts of protons are reported in parts per million downfield from tetramethylsilane (TMS: δ 0.00 ppm). Chemical shifts of carbons are referenced to the carbon resonances of the solvent (CDCl3: δ 77.0). Peaks are labeled as singlet (s), doublet (d), triplet (t), quartet (q) and multiplet (m). Optical rotations were measured on a Perkin Elmer digital polarimeter. Melting points were measured on a WRS-2A melting point apparatus and are uncorrected. Infrared (IR) spectra were recorded on a Bruker Tensor 37 spectrophotometer. Data are represented as follows: frequency of absorption (cm-1). Enantiomeric excesses were determined by HPLC using Daicel Chiralpak AD, OD column and eluting with a hexane/iPrOH solution. Isatin derivatives 1a-1k were prepared according to the similar reported procedures.[1] And Isocyanoacetate 3a-3d were prepared according to the similar reported procedures.[2]

    Materials

    Flash chromatography was performed over silica gel (200-300 mesh), purchased from HuangHai JiangYou Chemical Co., Ltd. Commercial reagents were used as received. The solvents were used as received in analytical grade.

    B) General procedure for the three-component reaction 1a (32.2 mg, 0.200 mmol), 2a (13.2 mg, 0.200 mmol), 3a (38.8 mg, 0.220 mmol), 4f (2.3 mg, 0.004 mmol) and DCM (2 mL) in a flask was stirred for 8 hr at r.t. After evaporation of the solvent under vacuum, the residue was separated by flash chromatography over silica gel to give 5a and 5a´ (70.6 g, 92% yield) as white solid.

    C) Preparation of racemic samples

    Racemic samples were prepared with Et3N instead of 4f following the general procedure.

    D) X-ray crystal structure information of 5g

    Single-crystal reflection data were collected on an Oxford Gemini S Ultra diffractometer with the enhance X-ray source of Cu-Kα radiation (λ = 1.54178 Å) using the ω-ϕ scan technique. Structural solution and refinement against F2 were carried out using the SHELXL programs.[3] All the non-hydrogen atoms were refined anisotropically. Hydrogen atoms were placed geometrically and located in the difference Fourier map. An ORTEP drawing of 5g is shown in Figure 1.

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Figure 1. X-ray structure of 5g

    CCDC-859158 contains the supplementary crystallographic data of 5g for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Tel: +44 (0) 1223 762911; E-mail: [email protected]].

    E) References

    1. D. J. Vyas; R. Frohlich; M. Oestreich. J. Org. Chem. 2010, 75, 6720. 2. R. S. Bon; C. Hong; M. J. Bouma; R. F. Schmitz; F. J. J. de Kanter; M. Lutz; A. L. Spek; R. V. A.

    Orru. Org. Lett. 2003, 5, 3759. 3. G. M. Sheldrick. SHELX 97, Program for Crystal Structure Solution and Refinement, Göttingen

    University, 1997.

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    F) NMR SPECTRA of products

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    G) HPLC Chromatograms of products

    N

    N

    OCOOMe

    NCNC

    5a

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    N

    N

    OCOOMe

    NCNC

    O

    5j

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    N

    N

    OCOOMe

    NCNC

    5k

    O

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    N

    N

    OCOOMe

    NCNC

    rac-5k'

    O

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    N

    NNCNC

    O

    OO

    rac-5l

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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    N

    NHNC

    NC

    OCOOMe

    rac-6a

    N

    NHNC

    NC

    OCOOMe

    6a

    Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012

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