Chiral Boron Complex-Promoted Asymmetric Diels-Alder Cycloaddition and Its Application in Natural Product Synthesis Xia Li, Jianguang Han, Alexander X. Jones and Xiaoguang Lei* School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, China National Institute of Biological Sciences (NIBS), Beijing, 102206, China Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Center for Life Sciences, Peking University, Beijing, 100871, China Email: xglei@pku.edu.cn Supporting Information Table of Contents Page I) General Information S2-S3 II) NMR spectra and chiral HPLC chromatography III) X-ray thermal ellipsoid plot for compound 51 S4 S51 S51-S53 S1
I) General Information 1 H NMR spectra were recorded on a 400 MHz spectrometer at ambient temperature (25 o C) with CDCl3 as the solvent unless otherwise stated. 13 C NMR spectra were recorded on a 100 MHz spectrometer (with complete proton decoupling) at ambient temperature; Chemical shifts are reported in parts per million relative to chloroform ( 1 H, δ 7.26; 13 C, δ 77.00). Data for 1 H NMR are reported as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, dd = double doublet, t = triplet, m = multiplet, br = broad) and coupling constants. High resolution mass spectra (HRMS) were obtained on a quadrupole time-of-flight (Q-TOF) mass spectrometer for the electrospray ionization (ESI) experiments. Infrared spectra were recorded on a spectrophotometer. High-resolution mass spectra were obtained using a FTMS Flash chromatography. Optical rotations were recorded on a digital polarimeter at 589 nm and are recorded as [α]d 25 (concentration in grams/100 ml solvent). The samples were analyzed by HPLC/MS on a Purification LC/MS system. The system was equipped with a C18 separation column (150*4.6 mm), equilibrated with HPLC grade water (solvent A) and HPLC grade methanol (solvent B) with a flow rate of 1.0 ml/min. Chiral HPLC analysis was performed on a HPLC system with chiral columns, the enantiomers were separated by using isopropanol and n-hexane as the mobile phase (1 ml/min) unless otherwise noted. Analytical thin layer chromatography was performed using 0.25 mm silica gel 60-F plates. Flash chromatography was performed using 200-400 mesh silica gel. All yields refer to chromatographically and spectroscopically pure materials, unless otherwise stated. All reagents were used as supplied by commercial vendors. Dichloromethane and toluene were distilled from calcium hydride, tetrahydrofuran was distilled from sodium/benzophenone ketyl prior to use. All reactions were carried out in oven-dried S2
glassware under argon atmosphere, unless otherwise noted. S3
II) NMR Spectra and chiral HPLC S4
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Racemate S6
Table 2, entry 1 R-BINOL L1 (2 equiv), 5 Å MS S7
Table 2, entry 2 R-BINOL-ArF L2 (2 equiv), 5 Å MS S8
Table 2, entry 3 R-BINOL-8H L3 (2 equiv), 5 Å MS S9
Table 2, entry 4 R-BINOL-8H-ArF L4 (2 equiv), 5 Å MS S10
Table 2, entry 5 (R,R)-TADDOL L5 (2 equiv), 5 Å MS S11
Table 2, entry 6 R-VANOL L6 (2 equiv), 5 Å MS S12
Table 2, entry 7 R-VANOL L6 (1.2 equiv), 5 Å MS S13
Further test the efficiency of the recovered chiral ligand: Racemate S14
Table 2, entry 7: test the efficiency of the recovered chiral ligand The first time R-VANOL L6 (1.2 equiv) S15
Table 2, entry 8: Further test the efficiency of the recovered chiral ligand The one cycle R-VANOL L6 (1.2 equiv) S16
Table 2, entry 9: Further test the efficiency of the recovered chiral ligand The two cycle R-VANOL L6 (1.2 equiv) S17
Table 2, entry 10 R-VAPOL L7 (2 equiv), 5 Å MS S18
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Racemate S20
R-VAPOL L7 (1.2 equiv), 5 Å MS S21
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Racemate S23
R-VANOL L6 S24
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Racemate S26
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Racemate S29
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Racemate S32
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Racemate S35
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Racemate S38
R-VANOL (1.2 equiv) S39
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Racemate S41
S-VANOL (1.2 equiv) S42
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Crystal data and structure refinement for endo-endo cycloadduct (51) Crystals of endo-endo cycloadduct 51 suitable for X-ray analysis were obtained by slow evaporation from DCM and toluene. Displacement ellipsoids are drawn at the 30% probability level. Bond precision: C-C = 0.0056 Å Wavelength = 0.71073 Å Cell: a= 31.426(3) b= 13.9013(12) c= 21.3552(17) alpha = 90 beta = 105.307(2) gamma = 90 Temperature 293 K Calculated Reported Volume 8998.3 (14) 8998.2 (13) Space group C 2/c C 2/c Hall group Sum formula C48 H52O10 Moiety formula -C 2yc S52 C48 H52O10
C48H52O10 Mr 788.90 788.89 Dx g cm -3 1.165 1.163 Z 8 8 Mu (mm -1 ) 0.081 0.081 F000 3360.0 3352.0 F000 3361.74 H,k,l max 36,16,25 36,16,25 Nerf 7670 7665 Tmin, Tmax 0.979,0.990 0.695,1.000 Tmin 0.966 Correction method= # Reported T Limits: Tmin=0.695 Tmax=1.000Abs Corr = MULTI-SCAN Data completeness= 0.999 Data completeness= 0.999 S = 1.019 Npar = Data completeness= 0.999 w R2(reflections)= 0.1434( 7665) S53
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