Ionic liquid effect over the Biginelli reaction under homogeneous and heterogeneous catalysis

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Supporting Information for Ionic liquid effect over the Biginelli reaction under homogeneous and heterogeneous catalysis Haline G. O. Alvim, a,b Tatiani B. de Lima, c Heibbe C. B. de Oliveira, a Fabio C. Gozzo, c Julio L. de Macedo, d Patricia V. Abdelnur, e Wender A. Silva, b * and Brenno A. D. Neto, a * a Laboratory of Medicinal and Technological Chemistry, University of Brasilia (IQ-UnB). Campus Universitario Darcy Ribeiro, CEP 70904970, P.O.Box 4478, Brasilia-DF, Brazil. b Laboratory for Bioactive Compounds Synthesis, University of Brasilia (IQ-UnB). Campus Universitario Darcy Ribeiro, CEP 70904970, P.O.Box 4478, Brasilia-DF, Brazil. c Institute of Chemistry, University of Campinas, Campinas, SP, Brazil. d Laboratory of Catalysis, Institute of Chemistry, University of Brasília, P.O. Box 4478, CEP 70904970, Brasília - DF, Brasil. e Embrapa Agroenergia, PqEB s/n Av. W3 Norte (final), Edifício Embrapa Agroenergia, CEP: 70770-901, P.O.Box 40315. E-mail: wender@unb.br, brenno.ipi@gmail.com S1

Summary Scheme S1 Page S3 Figure S1 Page S4 Figure S2 Page S4 Spectroscopic data for all compounds Pages S4-S6 Cartesian coordinates, energy and thermal corrections for all calculated structures Pages S7-S13 References Page S13 S2

Scheme S1. The three accepted mechanism for the Biginelli reaction. S3

80 70 60 50 Yield (%) 40 30 20 10 0 0 100 200 300 400 500 600 700 Time (min) Figure S1. Reaction profile (model reaction) conducted at 90 ºC, BMI.BF 4 (1 ml) and 3.00 mmol of each reagent and 7 mol% of the catalyst (MSI.Fe 2 Cl 7 ) affording 4a. All yields refer to the isolated product. 83.0643 N + N H N + N. N + N SO 3 H 205.0632 96.0622 O S O O + H + 123.0168 59.0566 0 25 50 75 100 125 150 175 200 m/z Figure S2. ESI(+)-QTOF product ion spectrum of the catalyst (MSI) 3 PW. MSI.Cl: 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.10 (s, 1H), 7.77 (s, 1H), 7.71 (s, 1H), 4.30 (t, 2H, J = 7.0 Hz), 3.87 (s, 3H), 2.45 (t, 2H, J = 7.1 Hz), 2.12-2.03 (m, 2H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 136.9, 123.8, 122.4, 47.7, 47.5, 35.7, 26.2. Ethyl-6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4a): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.22 (s, 1H), 7.76 (s, 1H), 7.29-7.18 (m,5h), 5.14 (s,1h), 3.97 (q, 2H, J = 6.8 Hz), 2.24 (s, 3H), 1.07 (t, 3H, J = 6.8 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 165.7, 152.6, 148.8, 145.3, 128.8, 127.7, 126.7, 99.7, 59.6, 54.4, 18.2, 14.5. FT- IR (KBr, cm -1 ): 3252, 3109, 2972, 1728, 1689, 1645, 1468, 1230, 1097, 778. m.p. 212-213 C (literature 1 212-213 C) and Rf 0.60 (Hexane/ AcOEt 7:3). White solid, method a 87%, method b 99%, method c 99%, method d 85% e method e 99%. S4

5-Acetyl-4-phenil-6-methyl-3,4-dihydropyrimidin-2(1H)-one (4b): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.19 (s, 1H), 7.84 (s, 1H), 7.32-7.22 (m, 5H), 5.25 (s, 1H), 3.43 (q, J = 6.2 Hz), 1.06 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 194.7, 152.6, 148.6, 144.6, 128.9, 128.8, 110.0, 56.5, 30.7, 19.3. FT-IR (KBr, cm -1 ): 3287, 3241, 2914, 1706, 1603, 1466, 1248, 764. m.p. 238-240 C (literature 2 238-240 C) and Rf 0.64 (Hexane/AcOEt 7:3). White solid, method a 76%, method b 96%, method c 82%, method d 79% e method e 99%. Ethyl-6-methyl-4-phenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4c): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 11.15 (s, 1H), 10.44 (s, 1H), 8.31-8.04 (m, 5H), 5.94 (d, 1H, J = 3.0 Hz), 4.75 (q,2h, J = 6.7Hz), 3.05 (s, 3H), 1.84 (t, 3H, J = 7.1 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 174.7, 166.9, 165.4, 145.9,130.1, 129.0, 128.8, 100.7, 60.1, 53.9, 17.7, 14.6. FT-IR (KBr, cm - 1 ): 3322, 3466, 3176, 3111, 1670, 1575, 1470, 1277, 1197, 1105, 696. m.p. 200-202 C (literature 2 200-202 C) and Rf 0.50 (Hexane/ AcoEt 7:3). Yellow solid, method a 43%, method b 88%, method c 99%, method d 98% e method e 99%. Ethyl-4-(3-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4d): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.14 (s, 1H), 9.93 (s, 1H), 8.46(s, 1H), 7.65 (t, 1H, J = 7.9 Hz), 7.44-7.36 (m, 3H), 5.82 (d,1h, J = 2.7 Hz), 4.76 (q, 2H, J = 7.2 Hz), 2.99 (s, 3H), 1.87 (t, 3H, J = 7.1 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 165.9, 157.8, 152.7, 148.6, 146.7, 129.8, 128.8, 117.3, 114.6, 99.8, 59.6, 54.3, 18.2, 14.6. FT-IR (KBr, cm -1 ): 3514, 3364, 3250, 3104, 2978, 1722, 1638, 1600, 1475, 1305, 1221, 1056, 771. m.p. 168-170 C (literature 2 168-170 C) and Rf 0.33 (Hexane/ AcOEt 7:3). White solid, method a 99%, method b 37%, method c 66%, method d 60% e method e 75%. Ethyl 6-methyl-4-(3-hydroxyphenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4e): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.28 (s, 1H), 9.59 (s, 1H), 9.44 (s, 1H), 7.09 (t, 1H, J = 7.9 Hz), 6.65 (m, 3H), 5.09 (d,1h, J = 2.7 Hz), 3.98 (q, 2H, J = 6.7 Hz), 2.27 (s, 3H), 1.08 (t, 3H, J = 6.9 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 174.6, 165.6, 157.9, 145.6, 145.2, 129.9, 117.5, 115.0, 113.8, 101.2, 60.5, 54.4, 17.6, 14.4. FT-IR (KBr, cm -1 ): 3304, 3179, 3109, 2982, 1662, 1573, 1479, 1375, 1293, 1196, 1117, 747. m.p. 180-181 C (literature 2 180-181 C) and Rf 0.24 (Hexane/ AcOEt 7:3). Yellow solid, method a 50%, method b 98%, method c 33%, method d 98% e method e 50%. Ethyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4f): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.39 (s, 1H), 8.16-7.68 (m, 4H), 3.89 (q, 2H, J = 2.7 Hz), 2.28 (s, 3H), 1.10 (t,3h, J = 6.9 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 165.1, 151.8, 149.5, 147.7, 147.0, 133.0, 130.3, 122.4, 121.0, 98.3, 59.4, 53.6, 17.9, 14.0. FT-IR (KBr, cm -1 ): 3330, 3213, 3105, 2965, 1709, 1631, 1520, 1456, 1343, 1221, 1084, 810, 686, 530. m.p. 240-242 C (literature 2 240-242 C) and Rf 0.85 (Hexane/ AcOEt 7:3). White solid, method a 41%, method b 81%, method c 69%, method d 63% e method e 98%. 5-acetyl-3,4-dihydro-6-methyl-4-(3-nitrophenyl)-pyrimidin- 2(1H)-one (4g): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.37 (s, 1H), 8.14-7.6 (m. 4H), 5.4 (d, 1H, J = 3Hz), 2.33 (s, 3H), 2.19 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 194.1, 152.0, 149.2, 147.9, 146.5, 133.0, 130.2, 122.4, 121.1, 109.5, 53.0, 30.7, 19.1. FT-IR (KBr, cm -1 ): 3357, 3271, 3057, 1721, 1683, 1591, 1532, 1347, 1239, 764, 693, 578. m.p. 261-262 C (literature 3 261-262 C) and Rf 0.88 (Hexane/ AcOEt 7:3). Yellow solid method a 57%, method b 93%, method c 54%, method d 63% e method e 98%. 1,2,3,4-tetrahydro-6-methyl-2-oxo-5-pyrimidinecarboxylic acid ethyl ester (4h): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 4.58 (q, 2H, J = 3.7 Hz), 3.43 (d, 2H), 1.07 (t, 3H, J = 7.0 Hz). FT-IR (KBr,cm -1 ): 3356, 2928, 1621, 1571, 1242, 664. m.p. 258-259 C (literature 2 258-259 C). White solid, method a 56%, method b 82%, method c 86%, method d 76% e method e 94%. 1,2,3,4-tetrahydro-4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-oxo-5-pyrimidinecarboxylic acid ethyl ester (4i): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.15 (s, 1H), 8.91 (s, 1H), 7.67 (s, 1H), 6.81-6.65 (m, 3H), 5.09 (s, 1H), 4.44 (q,2h), 3.99 (s, 3H), 2.46 (s, 3H), 1.06 (t, 3H, J = 5.2 Hz). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 165.9, 152.9, 148.2,147.7, 146.19, 136.3, 118.0, 115.7, 111.2, 100.1, 59.6, 55.9, 54.0, 18.1, 14.5. FT-IR (KBr, cm -1 ): 3542. 3242, 3115, 2972, 2922, 1703, 1642, 1509, 1219, 1086, 782. m.p. 228-229 C (literature 1 228-231 C) and Rf 0.85 (Hexane/ AcOEt 7:3). White solid, method a 59%, method b 43%, method c 46%, method d 80% e method e 99%. S5

2,3,4,6,7,8-hexahydro-4-(3-hydroxyphenyl)-2-thioxo-quinazolin-5(1H)-one (4j): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.57 (s, 1H), 9.64 (s, 1H), 9.42 (s, 1H), 7.10-7.05 (m, 4H), 5.08 (d, J = 3.3 Hz), 3.38 (s, 1H), 2.47 (q, 1H, J = 4.2 Hz), 1.96 (s, 1H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 194.4, 184.2, 174.8, 157.8, 151.0, 145.1, 129.9, 117.4, 113.7, 109.5, 52.1, 36.8, 25.7, 20.9. FT- IR (KBr, cm -1 ): 3408, 3284, 2916, 1620, 1447, 1356, 1175, 760. m.p. 229-231 C (literature 4 217-219 C) and Rf 0.81 (MeOH 100%). Yellow solid, method a 76%, method b 59%, method c 59%, method d 59% e method e 60%. 2,3,4,6,7,8-hexahydro-4-(3-hydroxyphenyl)-7,7-dimethyl-2-thioxo-5(1H)-quinazolinone (4k): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.56 (s, 1H, NH), 9.57, 9.23, 7.14-6.63 (m, 4H), 5.07 (d, 1H, J = 3.3 Hz), 1.99 (s, 2H), 1.74, 1.19 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 196.7, 194.3, 184.2, 174.8, 157.8, 151.0, 145.1, 129.9, 117.4, 109.5, 52.1, 36.8, 32.4, 25.7, 20.9. FT-IR (KBr, cm -1 ): 3400, 2957, 1644, 1585, 1463, 1364, 1193, 793, 692, 472. m.p. 220 C (literature 5 220 C) and Rf 0.17 (hexano/ AcoEt 7:3). Yellow solid, method a 21%, method b 87%, method c 21%, method d 53% e method e 60%. 5-acetyl-3,4-dihydro-6-methyl-4-(2-nitrophenyl)-pyrimidin-2(1H)-one (4l): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.22 (s, 1H), 9.08 (s, 1H), 7.85-6.51 (m. 4H), 4.13 (d, 1H, J = 3.9 Hz), 2.31 (s,3h), 2.11 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 157.8, 154.9, 148.5, 136.8, 134.6, 133.1, 129.0, 128.9, 124.6, 56.6, 29.0, 19.2. FT-IR (KBr, cm -1 ): 3470, 3442, 3371, 3286, 1672, 1592, 1514, 1372, 1199, 787, 586. m.p. 200 C (literature 6 239-242 C) and Rf 0.64 (Hexane/ AcOEt 7:3). Yellow solid, method a 65%, method b 98%, method c 70%, method d 70% e method e 86%. 1,2,3,4-tetrahydro-4-(2-hydroxyphenyl)-6-methyl-2-thioxo-5-pyrimidinecarboxylic acid ethyl ester (4m): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 9.67 (s, 1H), 9.12 (s, 1H), 7.20-7.16 (m, 2H), 6.94-6.79 (m, 2H), 5.44 (d, 1H, J = 2.7 Hz), 4.13, (q, 2H, J = 1.8 Hz), 1.77 (d, 3H), 1.21 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 176.8, 168.26, 150.9, 130.1, 129.2, 124.1, 121.3, 116.8, 100.0, 81.8, 61.2, 48.6, 23.8, 14.4. FT-IR (KBr, cm -1 ): 3328, 3201, 2975, 1721, 1565, 1505, 1383, 1260, 1182, 1089, 908, 758, 523. m.p. 175-176 C (literature 7 178-179 C) and Rf 0.35 (Hexane/ AcOEt 7:3). Yellow solid, method a 12%, method b 36%, method c 15%, method d 97% e method e 60%. 4-(1,3-benzodioxol-5-yl)-1,2,3,4-tetrahydro-6-methyl-2-thioxo-5-pyrimidinecarboxylic acid- ethyl ester (4n): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.34 (s, 1H), 9.63 (s, 1H), 6.88 (s, 1H), 6.72 (d, 2H, J = 1.5 Hz), 6.00 (s, 2H), 5.09 (d, 1H, J = 3.6 Hz), 2.29 (s, 3H), 1.12 (t, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 174.4, 166.5, 147.8, 147.1, 145.5, 137.8, 134.1, 120.1, 108.6, 107.2, 101.5, 60.0, 54.1, 17.6, 14.5. FT-IR (KBr, cm -1 ): 3320, 3185, 2978, 2892, 1163, 1573, 1492, 1336, 1235, 1202, 1107, 742. m.p. 175 C (literature 8 174-175 C) and Rf 0.55 (Hexane/ AcOEt 7:3). Yellow solid, method a 35%, method b 85%, method c 19%, method d 71% e method e 74%. 5-acetyl-3,4-dihydro-4-(3-hydroxyphenyl)-6-methyl-pyrimidin-2(1H)-one (4o): 1 H NMR (DMSO-d6, 300 MHz, δ ppm): 10.18 (s, 1H), 9.94 (s, 1H), 8.56 (s, 1H), 7.88 (t, 1H, J = 7.1 Hz), 7.42 (t, 1H, J =10.5 Hz), 5.94 (s, 1H), 3.04 (s, 3H), 2.85 (s, 3H). 13 C NMR (DMSO-d6, 75 MHz, δ ppm): 194.9, 157.9, 152.6, 148.4, 146.1, 130.0, 117.5, 114.8, 113.7, 110.0, 54.3, 30.7, 19.4. FT-IR (KBr, cm -1 ): 3248, 3107, 2942, 1707, 1657, 1606, 1462, 1235, 742. m.p. 214-215 C (literature 2 214-215 C) and Rf 0.77 (Hexane/ AcOEt 7:3). White solid, method a 76%, method b 99%, method c 33%, method d 65% e method e 85%. S6

Cartesian coordinates, energy and thermal corrections for all the calculated structures NTf 2 (trans) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -1827.29622257 hartree 0.050244 hartree 0.065255 hartree 0.066199 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.005424 hartree 1 16 0 1.152720 0.858639 0.081272 2 8 0 1.655989 1.858874 1.030628 3 8 0 0.907394 1.251850-1.311887 4 7 0 0.000025 0.000005 0.825821 5 16 0-1.152714-0.858637 0.081348 6 8 0-1.655924-1.858866 1.030742 7 8 0-0.907472-1.251857-1.311823 8 6 0 2.581269-0.376053-0.032334 9 9 0 3.647948 0.214899-0.613490 10 9 0 2.250766-1.450572-0.767232 11 9 0 2.961778-0.802709 1.186189 12 6 0-2.581272 0.376052-0.032180 13 9 0-2.250816 1.450566-0.767106 14 9 0-2.961708 0.802716 1.186364 15 9 0-3.647985-0.214907-0.613266 NTf 2 (cis) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -1827.29356663 hartree 0.050180 hartree 0.065262 hartree 0.066207 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.004363 hartree 1 16 0-1.448765-0.793396 0.442384 2 8 0-2.067807-0.960394 1.762554 3 8 0-1.702273-1.787377-0.611009 4 7 0 0.084185-0.355015 0.638987 5 16 0 1.248653-0.624377-0.459120 6 8 0 1.005122-0.092176-1.808988 7 8 0 1.895904-1.939044-0.336589 8 6 0-2.286105 0.776436-0.203021 9 9 0-3.615080 0.563485-0.328865 10 9 0-1.810541 1.142446-1.402518 11 9 0-2.116015 1.807396 0.648080 12 6 0 2.490092 0.576037 0.304045 S7

13 9 0 2.803337 0.253113 1.569619 14 9 0 2.038665 1.841974 0.288382 15 9 0 3.626412 0.534538-0.425700 Int I E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -494.70685173 hartree 0.155941 hartree 0.165691 hartree 0.166635 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.120224 hartree 1 6 0 0.000000 0.736266 0.000000 2 6 0-0.729891-0.487977 0.000000 3 6 0-0.114629-1.767793 0.000000 4 6 0-0.900389-2.907186 0.000000 5 6 0-2.302386-2.795717 0.000000 6 6 0-2.924034-1.541663 0.000000 7 6 0-2.145751-0.392095 0.000000 8 1 0 0.966071-1.875265 0.000000 9 1 0-0.434927-3.886853 0.000000 10 1 0-2.909171-3.696045 0.000000 11 1 0-4.005992-1.467403 0.000000 12 1 0-2.620483 0.585127 0.000000 13 7 0 1.306139 0.867686 0.000000 14 1 0 1.903377 0.042069 0.000000 15 1 0-0.579498 1.656118 0.000000 16 6 0 2.161534 2.064360 0.000000 17 7 0 1.540395 3.258084 0.000000 18 1 0 2.136788 4.075455 0.000000 19 1 0 0.544486 3.407119 0.000000 20 8 0 3.350861 1.853764 0.000000 Int II E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -955.03759357 hartree 0.311357 hartree 0.332740 hartree 0.333684 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.258927 hartree 1 6 0-0.483720 0.165542-0.720837 2 6 0-1.841946-0.371925-0.340538 3 6 0-2.272420-0.457550 0.992076 4 6 0-3.549356-0.937818 1.284773 5 6 0-4.405800-1.334402 0.254715 6 6 0-3.983420-1.256357-1.075262 7 6 0-2.706601-0.779494-1.370258 S8

8 1 0-1.623251-0.165535 1.811491 9 1 0-3.872411-1.004547 2.318457 10 1 0-5.397306-1.709250 0.487918 11 1 0-4.641455-1.572251-1.878261 12 1 0-2.378931-0.736876-2.407460 13 7 0-0.551546 1.719412-0.957034 14 1 0-1.232092 1.883825-1.705011 15 6 0-1.024080 2.610905 0.192477 16 8 0-2.197999 2.848429 0.277747 17 7 0-0.005693 3.010668 0.973483 18 1 0 0.962503 2.880680 0.703590 19 1 0-0.223412 3.664509 1.715370 20 1 0 0.408564 1.988162-1.252234 21 6 0 0.675837-0.182689 0.239750 22 6 0 0.791979-1.721641 0.489817 23 6 0 2.011727 0.424095-0.206631 24 8 0 0.819179-2.109121 1.635751 25 8 0 2.091436 1.549418-0.710039 26 8 0 3.042497-0.343647 0.048091 27 6 0 4.399438 0.167829-0.249926 28 1 0 4.435193 0.385729-1.319742 29 6 0 5.384900-0.898763 0.171190 30 1 0 5.232945-1.825520-0.388457 31 1 0 6.398901-0.540774-0.031778 32 1 0 5.305244-1.113275 1.240068 33 1 0 4.520540 1.100852 0.305101 34 6 0 0.859025-2.645818-0.701924 35 1 0-0.148499-2.780209-1.114682 36 1 0 1.500292-2.250308-1.496116 37 1 0 1.228328-3.620005-0.378899 38 1 0-0.230481-0.188163-1.725562 39 1 0 0.481721 0.240266 1.232130 Int I + NTf 2 (cis) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -2322.1577549386 hartree Counterpoise: BSSE energy = 0.003362841954 hartree 0.208877 hartree 0.235284 hartree 0.236229 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.147985 hartree 1 6 0 2.684041-0.896709 1.124592 2 6 0 3.276108-0.031010 0.147228 3 6 0 2.563211 0.966713-0.556277 4 6 0 3.227900 1.762682-1.478988 5 6 0 4.597075 1.577614-1.713291 6 6 0 5.316108 0.597932-1.017941 7 6 0 4.661878-0.199053-0.087280 8 1 0 1.504640 1.109542-0.381243 9 1 0 2.680514 2.524747-2.023319 10 1 0 5.106106 2.202930-2.440809 11 1 0 6.376568 0.462390-1.202612 12 1 0 5.208765-0.961632 0.460009 13 7 0 1.426397-0.993851 1.457761 S9

14 1 0 0.654706-0.504398 0.935644 15 1 0 3.335098-1.566429 1.686441 16 6 0 1.064190-1.933134 2.531636 17 7 0-0.197577-1.770508 2.947234 18 1 0-0.505139-2.370071 3.699554 19 1 0-0.777357-0.967491 2.683942 20 8 0 1.887623-2.733274 2.935071 21 16 0-0.957730-0.479310-1.554882 22 8 0 0.405144-0.788315-2.002126 23 8 0-1.863575 0.308895-2.383398 24 7 0-0.792010 0.044224 0.001670 25 16 0-1.941083 0.857144 0.832191 26 8 0-1.617395 0.620708 2.257026 27 8 0-3.314604 0.732657 0.362146 28 6 0-1.768743-2.176358-1.357604 29 9 0-1.896556-2.739967-2.563887 30 9 0-2.972320-2.073752-0.788634 31 9 0-0.995281-2.965551-0.589564 32 6 0-1.468678 2.668753 0.584853 33 9 0-1.601813 3.020177-0.696506 34 9 0-0.185997 2.864422 0.951883 35 9 0-2.254327 3.440901 1.340871 Int I + NTf 2 (trans) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -2322.157747089 hartree Counterpoise: BSSE energy = 0.003363151285 hartree 0.208875 hartree 0.235283 hartree 0.236227 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.147983 hartree 1 6 0 2.683634-0.899456 1.122723 2 6 0 3.276116-0.033066 0.146209 3 6 0 2.563611 0.965194-0.556918 4 6 0 3.228717 1.761673-1.478897 5 6 0 4.597970 1.576661-1.712771 6 6 0 5.316635 0.596460-1.017769 7 6 0 4.661961-0.201115-0.087928 8 1 0 1.504968 1.107892-0.382298 9 1 0 2.681566 2.524087-2.022974 10 1 0 5.107350 2.202392-2.439688 11 1 0 6.377154 0.460931-1.202116 12 1 0 5.208562-0.964145 0.459017 13 7 0 1.426036-0.996230 1.456155 14 1 0 0.654365-0.505644 0.934917 15 1 0 3.334436-1.570227 1.683619 16 6 0 1.063693-1.936849 2.528823 17 7 0-0.197834-1.774088 2.945224 18 1 0-0.505215-2.374517 3.696932 19 1 0-0.776527-0.969455 2.684551 20 8 0 1.886709-2.738260 2.930562 21 16 0-0.959889-0.477872-1.555324 22 8 0 0.402001-0.787888-2.004772 S10

23 8 0-1.866340 0.311512-2.382042 24 7 0-0.791320 0.044981 0.001176 25 16 0-1.938501 0.858252 0.833913 26 8 0-1.612397 0.621099 2.258086 27 8 0-3.312908 0.734648 0.366222 28 6 0-1.772129-2.174294-1.357570 29 9 0-1.901582-2.737557-2.563835 30 9 0-2.975064-2.070802-0.787408 31 9 0-0.998578-2.964305-0.590447 32 6 0-1.465702 2.669745 0.586487 33 9 0-1.600689 3.021637-0.694562 34 9 0-0.182417 2.864797 0.951614 35 9 0-2.249911 3.441937 1.343966 Int II + NTf 2 (cis) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -2782.478148904 hartree Counterpoise: BSSE energy = 0.004449014683 hartree 0.363734 hartree 0.401655 hartree 0.402599 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.287894 hartree 1 6 0 1.845642-0.274085 0.091057 2 6 0 2.764241-1.375431-0.403366 3 6 0 4.097580-1.487836 0.015318 4 6 0 4.901774-2.523963-0.461627 5 6 0 4.382474-3.458435-1.360266 6 6 0 3.055643-3.352275-1.784499 7 6 0 2.251244-2.315412-1.311154 8 1 0 4.526381-0.771459 0.708734 9 1 0 5.932884-2.597863-0.130430 10 1 0 5.009735-4.263880-1.730295 11 1 0 2.643872-4.073090-2.483850 12 1 0 1.220796-2.244145-1.648421 13 7 0 1.082971-0.728602 1.361707 14 1 0 0.505940-1.570146 1.103010 15 6 0 1.891012-1.100853 2.581033 16 8 0 2.282167-2.235293 2.701763 17 7 0 2.063854-0.061027 3.416665 18 1 0 1.663703 0.852049 3.211295 19 1 0 2.544105-0.235961 4.287625 20 1 0 0.401515 0.013640 1.576986 21 6 0 2.538876 1.098311 0.295075 22 6 0 3.276197 1.576557-0.988340 23 6 0 1.583046 2.176081 0.822426 24 8 0 4.409767 1.998129-0.870096 25 8 0 0.918052 2.022343 1.845113 26 8 0 1.596436 3.282499 0.109649 27 6 0 0.694007 4.366784 0.513226 28 1 0-0.316558 3.955795 0.527103 29 6 0 0.855688 5.483886-0.495413 30 1 0 0.577644 5.147230-1.497692 31 1 0 0.197468 6.313443-0.218059 32 1 0 1.884944 5.853585-0.517881 S11

33 1 0 0.972814 4.669707 1.525975 34 6 0 2.557913 1.501260-2.312755 35 1 0 2.601143 0.469977-2.684568 36 1 0 1.504138 1.779700-2.223106 37 1 0 3.066729 2.146589-3.030379 38 1 0 1.024723-0.143042-0.616624 39 1 0 3.320451 1.012781 1.058022 40 16 0-1.736484-1.897837-0.339445 41 8 0-0.815331-2.581847 0.606874 42 8 0-1.690093-2.275231-1.750455 43 7 0-1.561397-0.326163-0.000052 44 16 0-1.974365 0.902939-0.995720 45 8 0-2.747645 0.566296-2.187788 46 8 0-0.799890 1.788812-1.106099 47 6 0-3.445252-2.411536 0.280130 48 9 0-3.576869-3.736271 0.152438 49 9 0-4.396234-1.803248-0.434872 50 9 0-3.587888-2.080169 1.570663 51 6 0-3.150570 1.861588 0.127088 52 9 0-2.539875 2.212422 1.271058 53 9 0-4.230036 1.129536 0.420900 54 9 0-3.539278 2.977786-0.507113 Int II + NTf 2 (trans) E(M06-2X/6-311++g(2d,2p)//B3LYP/6-31+G(d,p))= -2782.474796169 hartree Counterpoise: BSSE energy = 0.004517634518 hartree 0.363821 hartree 0.401746 hartree 0.402690 hartree Thermal correction to Gibbs Free Energy at 298.15 K = 0.287487 hartree 1 6 0-1.588240 0.833030-0.003450 2 6 0-1.653115 2.236697-0.581458 3 6 0-2.701827 3.124004-0.299821 4 6 0-2.701310 4.409543-0.846365 5 6 0-1.652782 4.822162-1.670784 6 6 0-0.601770 3.944596-1.950151 7 6 0-0.602145 2.657651-1.412360 8 1 0-3.530907 2.830104 0.335220 9 1 0-3.521507 5.085343-0.624690 10 1 0-1.653875 5.822994-2.092036 11 1 0 0.222876 4.256478-2.583150 12 1 0 0.232009 1.994725-1.627407 13 7 0-0.636294 0.813641 1.218139 14 1 0 0.306638 1.021831 0.839678 15 6 0-0.889654 1.782300 2.354232 16 8 0-0.257741 2.809674 2.383796 17 7 0-1.823245 1.337967 3.209400 18 1 0-2.233478 0.405124 3.119884 19 1 0-2.004730 1.904291 4.026053 20 1 0-0.518528-0.172217 1.538580 21 6 0-2.964223 0.203956 0.322707 22 6 0-3.883422 0.075636-0.926846 S12

23 6 0-2.838092-1.138588 1.052864 24 8 0-5.071868 0.273655-0.768905 25 8 0-2.658004-1.199822 2.262936 26 8 0-2.938740-2.192506 0.261813 27 6 0-2.779181-3.516022 0.883276 28 1 0-1.775397-3.549380 1.312133 29 6 0-2.991897-4.552841-0.198908 30 1 0-2.250627-4.450614-0.995904 31 1 0-2.883648-5.550285 0.238803 32 1 0-3.993457-4.475446-0.632016 33 1 0-3.514164-3.592279 1.688169 34 6 0-3.286557-0.294978-2.261774 35 1 0-2.697879 0.544356-2.650585 36 1 0-2.619475-1.156760-2.170395 37 1 0-4.092434-0.515644-2.962849 38 1 0-1.053148 0.184360-0.700933 39 1 0-3.510475 0.845599 1.017104 40 16 0 1.570018-1.752433 0.404064 41 8 0 0.307318-1.787628 1.194344 42 8 0 2.752223-2.422002 0.931213 43 7 0 1.706528-0.210419-0.076339 44 16 0 3.057767 0.428762-0.779532 45 8 0 2.600491 1.605081-1.524393 46 8 0 3.957186-0.547433-1.387830 47 6 0 1.083470-2.725531-1.145542 48 9 0 0.740333-3.972713-0.786720 49 9 0 2.076096-2.779344-2.027210 50 9 0 0.011489-2.148260-1.733571 51 6 0 3.987639 1.147113 0.700498 52 9 0 4.386904 0.177635 1.528716 53 9 0 3.191061 1.992489 1.376515 54 9 0 5.057498 1.818340 0.259263 References 1 Ramos,L. M.; Tobio, A. Y. P. L.; Santos, M. R.; Oliveira, H. C. B.; Gomes, A. F.; Gozzo, F. C.; Oliveira, A. L.; Neto, B. A. D. J. Org. Chem. 2012, 77, 10184. 2 M. J. Frisch, G. W. Trucks, H. B. Schlegel et al., GAUSSIAN 09, Revision A.02, Gaussian, Inc., Wallingford CT, 2009. 3 P.J. Stephens, J.F. Devlin, C.F. Chabalowski, M.J. Frisch, J. Chem. Phys. 1993, 98, 11623. 4 Sarli, V.; Huemmer, S.; Sunder-Plassmann, N.; Mayer, T. U.; Giannis, A. ChemBioChem 2005, 6, 2005. 5 Shirini, F.; Zolfigol, M. A; Mollarazi, E. Synth.Commun.2006, 36, 2307. 6 Kamal, A.; KrishnaJ = i, T.; Azhar, M. A.Catal. Commun. 2007, 8, 1929 7 Zheng, R.; Wang, X.; Xu, H.; Du, J. Synth. Commun. 2006, 36, 1503. 8 Ghosh, R; Maiti, S.; Chakraborty, A. J. Mol. Catal. A: Chem. 2004, 217, 47. S13