Supporting Information

Transcription

1 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, , China National Institute of Biological Sciences (NIBS), Beijing, , 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, , China 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

2 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 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

3 glassware under argon atmosphere, unless otherwise noted. S3

4 II) NMR Spectra and chiral HPLC S4

5 S5

6 Racemate S6

7 Table 2, entry 1 R-BINOL L1 (2 equiv), 5 Å MS S7

8 Table 2, entry 2 R-BINOL-ArF L2 (2 equiv), 5 Å MS S8

9 Table 2, entry 3 R-BINOL-8H L3 (2 equiv), 5 Å MS S9

10 Table 2, entry 4 R-BINOL-8H-ArF L4 (2 equiv), 5 Å MS S10

11 Table 2, entry 5 (R,R)-TADDOL L5 (2 equiv), 5 Å MS S11

12 Table 2, entry 6 R-VANOL L6 (2 equiv), 5 Å MS S12

13 Table 2, entry 7 R-VANOL L6 (1.2 equiv), 5 Å MS S13

14 Further test the efficiency of the recovered chiral ligand: Racemate S14

15 Table 2, entry 7: test the efficiency of the recovered chiral ligand The first time R-VANOL L6 (1.2 equiv) S15

16 Table 2, entry 8: Further test the efficiency of the recovered chiral ligand The one cycle R-VANOL L6 (1.2 equiv) S16

17 Table 2, entry 9: Further test the efficiency of the recovered chiral ligand The two cycle R-VANOL L6 (1.2 equiv) S17

18 Table 2, entry 10 R-VAPOL L7 (2 equiv), 5 Å MS S18

19 S19

20 Racemate S20

21 R-VAPOL L7 (1.2 equiv), 5 Å MS S21

22 S22

23 Racemate S23

24 R-VANOL L6 S24

25 S25

26 Racemate S26

27 S27

28 S28

29 Racemate S29

30 S30

31 S31

32 Racemate S32

33 S33

34 S34

35 Racemate S35

36 S36

37 S37

38 Racemate S38

39 R-VANOL (1.2 equiv) S39

40 S40

41 Racemate S41

42 S-VANOL (1.2 equiv) S42

43 S43

44 S44

45 S45

46 S46

47 S47

48 S48

49 S49

50 S50

51 S51

52 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 = Å Wavelength = Å Cell: a= (3) b= (12) c= (17) alpha = 90 beta = (2) gamma = 90 Temperature 293 K Calculated Reported Volume (14) (13) Space group C 2/c C 2/c Hall group Sum formula C48 H52O10 Moiety formula -C 2yc S52 C48 H52O10

53 C48H52O10 Mr Dx g cm Z 8 8 Mu (mm -1 ) F F H,k,l max 36,16,25 36,16,25 Nerf Tmin, Tmax 0.979, ,1.000 Tmin Correction method= # Reported T Limits: Tmin=0.695 Tmax=1.000Abs Corr = MULTI-SCAN Data completeness= Data completeness= S = Npar = Data completeness= w R2(reflections)= ( 7665) S53

54 S54