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
2
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
3
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
4
F) NMR SPECTRA of products
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
5
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
6
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
7
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
8
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
9
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
10
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
11
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
12
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
13
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
14
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
15
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
16
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
17
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
18
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
19
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
20
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
21
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
22
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
23
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
24
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
25
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
26
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
27
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
28
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
29
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
30
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
31
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
32
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
33
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
34
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
35
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
36
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
37
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
38
N
N
OCOOMe
NCNC
O
5j
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
39
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
40
N
N
OCOOMe
NCNC
5k
O
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
41
N
N
OCOOMe
NCNC
rac-5k'
O
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
42
N
NNCNC
O
OO
rac-5l
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
43
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
44
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
45
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
46
Electronic Supplementary Material (ESI) for Organic & Biomolecular ChemistryThis journal is © The Royal Society of Chemistry 2012
47
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
/ColorImageDict > /JPEG2000ColorACSImageDict > /JPEG2000ColorImageDict > /AntiAliasGrayImages false /CropGrayImages true /GrayImageMinResolution 150 /GrayImageMinResolutionPolicy /OK /DownsampleGrayImages false /GrayImageDownsampleType /Bicubic /GrayImageResolution 150 /GrayImageDepth 8 /GrayImageMinDownsampleDepth 2 /GrayImageDownsampleThreshold 1.50000 /EncodeGrayImages true /GrayImageFilter /FlateEncode /AutoFilterGrayImages false /GrayImageAutoFilterStrategy /JPEG /GrayACSImageDict > /GrayImageDict > /JPEG2000GrayACSImageDict > /JPEG2000GrayImageDict > /AntiAliasMonoImages false /CropMonoImages true /MonoImageMinResolution 1200 /MonoImageMinResolutionPolicy /OK /DownsampleMonoImages false /MonoImageDownsampleType /Bicubic /MonoImageResolution 1200 /MonoImageDepth -1 /MonoImageDownsampleThreshold 1.50000 /EncodeMonoImages true /MonoImageFilter /FlateEncode /MonoImageDict > /AllowPSXObjects false /CheckCompliance [ /None ] /PDFX1aCheck false /PDFX3Check false /PDFXCompliantPDFOnly false /PDFXNoTrimBoxError true /PDFXTrimBoxToMediaBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXSetBleedBoxToMediaBox true /PDFXBleedBoxToTrimBoxOffset [ 0.00000 0.00000 0.00000 0.00000 ] /PDFXOutputIntentProfile (None) /PDFXOutputConditionIdentifier () /PDFXOutputCondition () /PDFXRegistryName () /PDFXTrapped /False
/CreateJDFFile false /Description >>> setdistillerparams> setpagedevice