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 305817 Ph.: +91-1463-238755 Fax: +91-1463-238722 e-mail: easwar.srinivasan@curaj.ac.in SUPPORTING INFORMATION Contents S. No. Detail Page No. 1 HPLC data of the aldol adducts SI-2 SI-20 2 3 1 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
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
Table 3, Entry 1 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 254 nm SI-3
Table 3, Entry 2 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 1 mlmin -1, = 254 nm SI-4
Table 3, Entry 3 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 230 nm SI-5
Table 3, Entry 4 Daicel CHIRALCEL OD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 217 nm SI-6
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
Table 3, Entry 6 Daicel CHIRALPAK AD-H, hexane/2-propanol = 92:8, flow rate: 0.5 mlmin -1, = 254 nm SI-8
Table 3, Entry 7 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 1.0 mlmin -1, = 254 nm SI-9
Table 3, Entry 8 Daicel IC, hexane/2-propanol = 90:10, flow rate: 1.5 mlmin -1, = 210 nm SI-10
Table 3, Entry 9 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 220 nm SI-11
Table 3, Entry 10 Daicel CHIRALCEL OD-H, hexane/2-propanol = 97:3, flow rate: 0.8 mlmin -1, = 210 nm SI-12
Table 3, Entry 11 Daicel CHIRALPAK AD-H, hexane/2-propanol = 90:10, flow rate: 0.5 mlmin -1, = 220 nm SI-13
Table 3, Entry 12 Daicel CHIRALCEL OD-H, hexane/2-propanol = 90:10 flow rate: 0.5 mlmin -1, = 220 nm SI-14
Table 3, Entry 13 Daicel IC, hexane/2-propanol = 90:10, flow rate: 1.5 mlmin -1, = 210 nm SI-15
Table 3, Entry 14 Daicel CHIRALPAK AD-H, hexane/2-propanol = 75:25, flow rate: 1.0 mlmin -1, = 254 nm SI-16
Table 3, Entry 15 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 1.0 mlmin -1, = 254 nm SI-17
Table 4, Entry 1 Daicel CHIRALPAK AD-H, hexane/2-propanol = 95:5, flow rate: 0.5 mlmin -1, = 254 nm SI-18
Table 4, Entry 3 Daicel IC, hexane/2-propanol = 92.5:7.5, flow rate: 0.8 mlmin -1, = 254 nm SI-19
Scheme 3, aldol adduct 11 Daicel CHIRALPAK IC, hexane/2-propanol = 70:20, flow rate: 1.0 mlmin -1, = 254 nm SI-20
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
Table 3 Entry 1 SI-22
Table 3, Entry 2 SI-23
Table 3, Entry 3 SI-24
Table 3, Entry 4 SI-25
Table 3, Entry 5 SI-26
Table 3, Entry 6 SI-27
Table 3, Entry 7 SI-28
Table 3, Entry 8 SI-29
Table 3, Entry 9 SI-30
Table 3, Entry 10 SI-31
Table 3, Entry 11 SI-32
Table 3, Entry 12 SI-33
Table 3, Entry 13 SI-34
Table 3, Entry 14 SI-35
Table 3, Entry 15 SI-36
Table 4, Entry 1 SI-37
Aldol adduct of 4-methyl cyclohexanone and 4-nitrobenzaldehyde (Scheme 3) SI-38
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
SI-40
SI-41
SI-42
SI-43
SI-44
SI-45
SI-46
SI-47
SI-48
SI-49
SI-50
SI-51
SI-52
SI-53
SI-54
SI-55
SI-56
SI-57
SI-58
SI-59
SI-60
SI-61
SI-62
SI-63
SI-64
SI-65
SI-66
SI-67
SI-68
SI-69
SI-70
SI-71
SI-72
SI-73
SI-74
SI-75
SI-76
1 H, 13 C NMR and Mass spectra of the catalysts 1b & 1c and the catalyst precursors SI-77
SI-78
SI-79 [M + H] + calculated for C 12 H 16 N 3 O 3 : 250.1186
SI-80
SI-81
SI-82 [M + H] + calculated for C 12 H 16 N 3 O 3 : 250.1186
SI-83
SI-84
SI-85 [M + H] + calculated for C 27 H 28 N 3 O 5 : 474.2023
SI-86
SI-87
SI-88 [M + Na] + calculated for C 27 H 27 N 3 O 5 Na: 496.1843