Probing the Synergistic Catalytic Model: A Rationally Designed Urea-Tagged Proline Catalyst for the Direct Asymmetric Aldol Reaction

Transcription

1 Probing the Synergistic Catalytic Model: A Rationally Designed Urea-Tagged Proline Catalyst for the Direct Asymmetric Aldol Reaction Meeta Bhati, Kiran Kumari and Srinivasan Easwar* Department of Chemistry, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, NH-8, Bandarsindri, Distt. Ajmer, Rajasthan Ph.: Fax: easwar.srinivasan@curaj.ac.in SUPPORTING INFORMATION Contents S. No. Detail Page No. 1 HPLC data of the aldol adducts SI-2 SI H NMR spectra of the crude reaction mixtures (determination of diastereomeric ratio) SI-21 SI-38 1 H and 13 C NMR spectra of the purified aldol adducts SI-39 SI-76 4 Spectral data of the catalysts and catalyst precursors SI-77 SI-88 General Diastereomeric ratios were calculated from the 1 H NMR of the crude reaction mixtures. Since all the aldol products are isolated as a mixture of syn and anti diastereomers, all the 1 H and 13 C NMR spectra provided here are of the respective isolated diastereomeric mixture. 1 H and 13 C NMR spectra were recorded on a Brucker Avance 500 MHz NMR Spectrometer. Mass spectra were obtained using a HRMS-ESI-Q-Time of Flight LC-MS (Synapt G2, Waters). Chiral HPLC studies were carried out on a Shimadzu LC-2010CHT HPLC system. SI-1

2 Table 1, Entry 2 HPLC Data Daicel CHIRALPAK AD-H, hexane/2-propanol = 87.5:12.5, flow rate: 0.8 mlmin -1, = 254 nm SI-2

3 Table 3, Entry 1 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 254 nm SI-3

4 Table 3, Entry 2 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 1 mlmin -1, = 254 nm SI-4

5 Table 3, Entry 3 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 230 nm SI-5

6 Table 3, Entry 4 Daicel CHIRALCEL OD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 217 nm SI-6

7 Table 3, Entry 5 Daicel CHIRALPAK AD-H, hexane/2-propanol = 91.5:9.5, flow rate: 0.5 mlmin -1, = 254 nm SI-7

8 Table 3, Entry 6 Daicel CHIRALPAK AD-H, hexane/2-propanol = 92:8, flow rate: 0.5 mlmin -1, = 254 nm SI-8

9 Table 3, Entry 7 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 1.0 mlmin -1, = 254 nm SI-9

10 Table 3, Entry 8 Daicel IC, hexane/2-propanol = 90:10, flow rate: 1.5 mlmin -1, = 210 nm SI-10

11 Table 3, Entry 9 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 220 nm SI-11

12 Table 3, Entry 10 Daicel CHIRALCEL OD-H, hexane/2-propanol = 97:3, flow rate: 0.8 mlmin -1, = 210 nm SI-12

13 Table 3, Entry 11 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 220 nm SI-13

14 Table 3, Entry 12 Daicel CHIRALCEL OD-H, hexane/2-propanol = 90:10 flow rate: 0.5 mlmin -1, = 220 nm SI-14

15 Table 3, Entry 13 Daicel IC, hexane/2-propanol = 90:10, flow rate: 1.5 mlmin -1, = 210 nm SI-15

16 Table 3, Entry 14 Daicel CHIRALPAK AD-H, hexane/2-propanol = 75:25, flow rate: 1.0 mlmin -1, = 254 nm SI-16

17 Table 3, Entry 15 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 1.0 mlmin -1, = 254 nm SI-17

18 Table 4, Entry 1 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 254 nm SI-18

19 Table 4, Entry 3 Daicel IC, hexane/2-propanol = 92.5:7.5, flow rate: 0.8 mlmin -1, = 254 nm SI-19

20 Scheme 3, aldol adduct 11 Daicel CHIRALPAK IC, hexane/2-propanol = 70:20, flow rate: 1.0 mlmin -1, = 254 nm SI-20

21 Determination of Diastereomeric Ratios (anti:syn) of the aldol adducts: 1 H NMR spectra of the crude reaction mixtures Table 1, Entry 2 SI-21

22 Table 3 Entry 1 SI-22

23 Table 3, Entry 2 SI-23

24 Table 3, Entry 3 SI-24

25 Table 3, Entry 4 SI-25

26 Table 3, Entry 5 SI-26

27 Table 3, Entry 6 SI-27

28 Table 3, Entry 7 SI-28

29 Table 3, Entry 8 SI-29

30 Table 3, Entry 9 SI-30

31 Table 3, Entry 10 SI-31

32 Table 3, Entry 11 SI-32

33 Table 3, Entry 12 SI-33

34 Table 3, Entry 13 SI-34

35 Table 3, Entry 14 SI-35

36 Table 3, Entry 15 SI-36

37 Table 4, Entry 1 SI-37

38 Aldol adduct of 4-methyl cyclohexanone and 4-nitrobenzaldehyde (Scheme 3) SI-38

39 1 H and 13 C NMR spectra of the isolated aldol adducts (all the spectra in this section represent the anti + syn diastereomeric mixture of the respective aldol adduct that was isolated) SI-39

40 SI-40

41 SI-41

42 SI-42

43 SI-43

44 SI-44

45 SI-45

46 SI-46

47 SI-47

48 SI-48

49 SI-49

50 SI-50

51 SI-51

52 SI-52

53 SI-53

54 SI-54

55 SI-55

56 SI-56

57 SI-57

58 SI-58

59 SI-59

60 SI-60

61 SI-61

62 SI-62

63 SI-63

64 SI-64

65 SI-65

66 SI-66

67 SI-67

68 SI-68

69 SI-69

70 SI-70

71 SI-71

72 SI-72

73 SI-73

74 SI-74

75 SI-75

76 SI-76

77 1 H, 13 C NMR and Mass spectra of the catalysts 1b & 1c and the catalyst precursors SI-77

78 SI-78

79 SI-79 [M + H] + calculated for C 12 H 16 N 3 O 3 :

80 SI-80

81 SI-81

82 SI-82 [M + H] + calculated for C 12 H 16 N 3 O 3 :

83 SI-83

84 SI-84

85 SI-85 [M + H] + calculated for C 27 H 28 N 3 O 5 :

86 SI-86

87 SI-87

88 SI-88 [M + Na] + calculated for C 27 H 27 N 3 O 5 Na: