Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is The Royal Society of Chemistry 2015 SUPPORTIG IFORMATIO Organocatalytic asymmetric intramolecular aza-enry reaction: Facile synthesis of trans-2,3-disubstituted tetrahydroquinolines Rajendra Maity and Subhas Chandra Pan * Department of Chemistry, Indian Institute of Technology Guwahati, orth Guwahati, Assam, 781039 span@iitg.ernet.in Table of Contents 1. General procedure of the synthesis of nitro-amine S2 2. Catalyst, solvent and temperature screening S3-S6 3. Crystal data S7-S8 4. Absolute configuration and References S9 5. MR data S10-S28 6. PLC data S29-S53 S1
General procedure for the synthesis of nitro-amine: R CO O 2 S 1 R= -, -5Cl, -6Cl, 1.MeO 2, 1M ao; 8M Cl 2.MsCl, DIPEA O 2-4Me 2, -5CF 3 S 2 80% R O 2 O C 2 O 100 o C, neat O OC 2 5 R O 2 2, Pd/C,MeO R O 2 O 2 2 S 3 80% S 4 75% S 2, S 4 were prepared by previously reported procedure 1, S 3 was prepared by previously reported procedure 2. S2
Preliminary Catalyst screening: 2 O 2 + PhCO Catalyst (10mol%) C 2 Cl 2 :pentane (1:5) 0.2 M, 3days,RT O 2 CF 3 CF 3 S S O O CF 3 75% Yield -60 ee CF 3 55% Yield 00 ee CF 3 o reaction CF 3 O O O o reaction CF 3 CF 3 Bui ibu O S 55% Yield 5% ee Bn O S o reaction O O O O S CF 3 CF 3 MeO P O O O 30% Yield o ee 70% Yield o ee o reaction MeO MeO MeO CF 3 CF 3 O O S O S TBDPSO 47% Yield 37%ee CF 3 45% Yield 30%ee CF 3 50% Yield 5%ee MeO MeO MeO O S O S 70% Yield 69% ee F 3 C CF 3 50% Yield 6% ee MeO OMe 60% Yield 5% ee S3
MeO O MeO S ibu S S 60% Yield 7% ee O ibu F 3C CF 3 80% Yield 67% ee F 3C CF 3 73% Yield 42% ee MeO S S S 85% Yield -60% ee F 3 C CF 3 F 3 C CF 3 80% Yield -60% ee F 3C CF 3 81% Yield 55% ee MeO S F 3C 85% Yield 74% ee CF 3 S4
Preliminary solvent screening using catalyst (V): O 2 2 + PhCO Catalyst V (10 mol%) Solvent (0.2 M), RT, 3days O 2 Ph o. Solvent Yield (%) a ee b 1. Ethanol 70-2. Toluene 70 48 3. CCl 3 75 66 4. C 2 Cl 2 78 58 5. Benzene 80 67 6. PhCF 3 78 60 7. Chlorobenzene 75 60 8. Ether 80 70 9. MTBE 70 70 10. CCl 4 80 57 11. 1 2 Dichloroethane 70 52 12. Cyclohexane:C 2 Cl 2 (5:1) 75 54 13. n-exane:c 2 Cl 2 (5:1) 80 72 14. Pentane:C 2 Cl 2 (5:1) 85 74 15. eptane:c 2 Cl 2 (5:1) 78 69 16. exane:ccl 3 (5:1) 75 50 17. Benzene (MS 4 A o ) 50 53 18. Benzene:CCl 3 (5:1) 70 66 a Isolated yield after silica gel column chromatography. b Determined by PLC using stationary phase chiral column. S5
Preliminary temperature screening using the catalyst V: O 2 ΝΗ 2 + PhCO Catalyst V(10 mol%) Pentane:C 2 Cl 2 (5:1) Temp., 3 days Trans (a) O 2 + Cis (b) O 2 o Temp. Overall Yield dr(a:b) ee (a) 1 RT 85% 100:0 74% 2 0 o C 85% 1:1 80% 3-20 o C 85% 1:1 80% S6
CRYSTAL DATA OF COMPOUD (CCDC 1048919) 3f: ORTEP STRUCTURE Crystal data and structure refinement for CIRAL COMPOUD 3f Identification code RM-O2-4Br-CIRAL Empirical formula C 15 13 Br 2 O 2 Formula weight 333.18 Temperature/K 296(2) Crystal system orthorhombic Space group P2 1 2 1 2 1 a/å 5.947(3) b/å 7.118(3) c/å 32.870(11) α/ 90.00 β/ 90.00 γ/ 90.00 Volume/Å 3 1391.4(10) S7
Z 4 ρ calc mg/mm 3 1.591 m/mm -1 2.957 F(000) 672.0 Crystal size/mm 3 0.32 0.28 0.20 2Θ range for data collection 2.48 to 52.54 Index ranges -7 h 7, -8 k 7, -36 l 40 Reflections collected 13277 Independent reflections 2607[R(int) = 0.0576] Data/restraints/parameters 2607/0/181 Goodness-of-fit on F 2 0.903 Final R indexes [I>=2σ (I)] R 1 = 0.0416, wr 2 = 0.1129 Final R indexes [all data] R 1 = 0.0824, wr 2 = 0.1446 Largest diff. peak/hole / e Å -3 0.51/-0.51 Flack parameter -0.011(19) S8
(2R, 3S)-1,2,3,4-tetrahydro-3-nitro-2-phenylquinoline (3a): O 2 Absolute configuration: The optical rotation of 3a was [α] D 23 = +42.0 (c 0.17, CCl 3 ). As, it was opposite to the reported compound 3, the absolute configuration was determined to be (2R, 3S). References: 1. J. C. Anderson, A. oble, P. R. Torres, Tetrahedron Lett., 2012, 53, 5707. 2. P. Chauhan, K. Kaur,. Bala, V. Kumar, S. S. Chimni, Indian J. Chem., Sect B, 2011, 50B, 304. 3. X.-F. Cai, M.-W. Chen, Z.-S. Ye, R.-. Guo, L. Shi, Y.-Q. Li, Y.-G. Zhou, Chem. Asian J., 2013, 8, 1381. S9
MR Data of the Products: O 2 3a O 2 3a S10
O 2 3b Me O 2 3b Me S11
O 2 3c O 2 3c S12
O 2 3d O 2 3d S13
O 2 3e Cl O 2 3e Cl S14
O 2 3f Br O 2 3f Br S15
O 2 3g F O 2 3g F S16
O 2 3h OMe O 2 3h OMe S17
O 2 3i O 2 3i S18
O 2 3j Cl O 2 3j Cl S19
O 2 3k Br O 2 3k Br S20
O 2 3l Me Me O 2 3l Me Me S21
O 2 3m O 2 3m S22
O 2 3n O 2 3n S23
O 2 3o O 2 3o S24
Cl O 2 3p Cl O 2 3p S25
Cl O 2 3q Cl O 2 3q S26
O 2 3r O 2 3r S27
F 3 C O 2 3s F 3 C O 2 3s S28
PLC data of the Products: O 2 3a O 2 3a S29
O 2 3a O 2 3b Me S30
O 2 3b Me O 2 3b Me S31
O O 2 2 3c O 2 3c S32
O 2 3d O 2 3d S33
O 2 3e Cl O 2 3e Cl S34
O 2 3e Cl O 2 3f Br S35
O 2 3f Br O 2 3f Br S36
O 2 3g F O 2 3g F S37
O 2 3g F O 2 3h OMe S38
O 2 3h OMe O 2 3i S39
O 2 3i O 2 3i S40
O 2 3j Cl O 2 3j Cl S41
O 2 3j Cl O 2 3k Br S42
O 2 3k Br O 2 3l Me Me S43
O 2 3l Me Me O 2 3l Me Me S44
O 2 3m O 2 3m S45
O 2 3n O 2 3n S46
O 2 3o O 2 3o S47
Cl O 2 3p Cl O 2 3p S48
Cl O 2 3p Cl O 2 3q S49
Cl O 2 3q Cl O 2 3q S50
O 2 3r O 2 3r S51
O 2 3r F 3 C O 2 3s S52
F 3 C O 2 3s F 3 C O 2 3s S53