Supporting Information

Supporting Information Rh(II)-Catalyzed Transannulation of N-Sulfonyl-1,2,3-Triazoles with 2,1-Benzisoxazoles or 1,2-Benzisoxazoles Xiaoqiang Lei, Mohan Gao, Yefeng Tang*,,, E-mail: yefengtang@tsinghua.edu.cn School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Medical School, Sichuan University, Chengdu 610041, China Beijing National Laboratory for Molecular Sciences (BNLMS), Beijing 100190, China Table of Contents 1. General Information 2 2. Supplementary Schemes and Figures 2 3. General Procedure for the Synthesis of 2,1-Benzisoxazoles and 1,2-Benzisoxazoles 4. General Procedure for the Transannulation of 1,2,3-Triazoles with 2,1-Benzoisoxazoles and 1,2-Benzisoxazoles 6 6 5. Analysis Data of 2,1-Benzoisoxazoles and 1,2-Benzisoxazoles 7 6. Analysis Data of Quinazolines and Imidazoles 9 7. NMR Spectra of 2,1-Benzoisoxazole and 1,2-Benzisoxazoles 20 8. NMR Spectra of Quinazolines and Imidazoles 26 9. X-ray Crystallographic Structures of 3a and 5f 70 1

1. General Information 1 H NMR, 13 C NMR and 19 F NMR spectra were recorded on Bruker AV400 spectrometer. TMS was used as internal standard for 1 H NMR (7.26 ppm), and solvent signal was used as reference for 13 C NMR (CDCl 3, 77.16 ppm). The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, td = triple doublet, qd = quarter doublet, m = multiplet. High-resolution mass spectra (HRMS) were recorded on a Waters Xevo G2 QTOF MS. Reactions were monitored by Thin Layer Chromatography on plates (GF 254 ) supplied by Yantai Chemicals (China) using UV light as visualizing agent and an ethanolic solution of Potassium permanganate, and heat as developing agents. If not specially mentioned, flash column chromatography uses silica gel (200-300 mesh) supplied by Tsingtao Haiyang Chemicals (China). Solvent purification was conducted according to Purification of Laboratory Chemicals (Peerrin, D. D.; Armarego, W. L. and Perrins, D. R., Pergamon Press: Oxford, 1980). Yields refer to chromatographically and spectroscopically ( 1 H NMR) homogeneous materials. 2. Supplementary Schemes and Figures Scheme S-1. Original Design of Rh(II)-Catalyzed [3+3] Cycloaddition of 1,2,3-Triazole and Benzisoxazoles 2

Scheme S-2. Crossover Experiment A 10 ml pressure tube, fitted with a rubber septum, was charged with 4a (0.07 mmol, 1.0 equiv) and 4b (0.07 mmol, 1.0 equiv). The reaction vessel was added freshly distilled 1,2-DCE (1.0 ml), sealed with a teflon screwcap and then placed in an oil bath preheated to 140 C. The resulting solution was heated at this temperature for 4 h. After consumption of the start materials monitored by TLC analysis, the reaction was cooled to ambient temperature. The solvent was removed in vacuo, and the resulting residue was submitted to flash chromatography (SiO 2, hexane/etoac) to obtain the corresponding products 3a, 3b, 3ab, 3ba. Scheme S-3. Mechanism Rationalization of 1,3-Sulfonyl Migration 3

In the proposed mechanism (Scheme 5, main text), the transformation from 4 to F involves a 1,3-sulfonyl migration. In theory, the 1,3-sulfonyl migration could proceed through either an intermolecular or an intramolecular process. To get deep insight into the mechanism, we conducted a crossover experiment as shown in Scheme S-2. It turned out that all of the four possible products (3a, 3b, 3ab, 3ba) could be identified in the crossover experiment, which implied that an intermolecular mechanism (Scheme S-3a) might be favorable. However, among the four products, the normal migration products 3a (from 4a) and 3b (from 4b) were isolated as major products (ca. 50 % yields), and the crossover products 3ab and 3ba formed only as minor products (ca. 8 % yields). The observed product distribution appears unusual, since if the 1,3-sulfonyl migration is totally an intermolecular process, the ratio of the normal products vs the crossover products should be close to 1:1. In this context, the 1,3-sulfonyl migration displayed some property similar to that of intramolecular process. Given above results, a stepwise 1,3-sulfonyl migration involving a close ion-pair intermediate or intermolecular hydrogen bonding interaction is more likely responsible for the transformation from 4 to F (Scheme S-3c). In this scenario, 4 first undergoes elimination of TsH to give intermediate E. Once generated, E and TsH could rapidly form a close ion-pair as represented by I-1, which then undergoes 1,6-addition to give the product F. Alternatively, an intermolecular hydrogen bonding interaction might also exist between E and TsH, thus making the 1,3-sulfonyl migration like an intramolecular process rather than intermolecular one. The mechanism outlined in Scheme S-3c could account for the observed product distribution in the crossover experiment. For the limit space in the main manuscript, we choose to include this part of work in the supporting information. Scheme S-4. Identification of 1,3-Sulfonyl Migration Product F To get further insight into the proposed mechanism, the intermediacy of F was also experimentally validated. When we performed the transformation from 4a to 3a under N 2 protection, we observed the formation of a major intermediate on the TLC (Scheme S-4). However, this intermediate was quite unstable and rapidly converts to 3a upon exposure to air. Thus, we could not obtain a pure compound for full structural assignment. The crude 1 H NMR of the reaction mixtures after rapid chromatography purification is provided in Figure S-1, from which we could tentatively assign the intermediate to be F based on some characteristic signals as well as LC-MS data. Figure S-2 includes the crude 1 H NMR of the reaction mixture after exposure to air for 3-4 h, which shows that the intermediate F totally converted into 3a via oxidation. 4

Figure S-1. Crude 1 H NMR Spectrum of the Mixture of F and 3a (CDCl 3, 400 MHz) Figure S-2. Crude 1 H NMR Spectrum of 3a (CDCl 3, 400 MHz) 5

3. General Procedure for the Synthesis of 2,1-Benzisoxazoles and 1,2-Benzisoxazoles A round bottom flask equipped with a magnetic stirrer bar was charged with the nitrophenyl-ethanone (1.00 mmol) in EtOAc MeOH (1:1; 5 ml). SnCl. 2 H 2 O (3.00 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between DCM (30 ml) and NaHCO 3 (20 ml). The aqueous phase was extracted with DCM (3 10 ml) and the organic portions was combined, washed with H 2 O (10 ml), saturated aqueous NaCl (10 ml), dried over MgSO 4, filtered and reduced in vacuo. The residue was purified by column chromatography (SiO 2, hexane/ EtOAc) to afford the corresponding 2,1-benzisoxazoles. A mixture of Ph 3 P (1.5 mmol, 1.5 equiv) and DDQ (1.5 mmol, 1.5 equiv) in dry CH 2 Cl 2 (5 ml) was stirred at room temperature for 1 min. Salicylaldoxime (1 mmol, 1.0 equiv) was then added. The color of the reaction mixture changed from green to brown in 1 min. GC or TLC monitoring showed completion of the reaction, and the solvent was evaporated. Column chromatography of the crude mixture on silica gel using n-hexane and ethyl acetate (3:1) as eluent gave the desired 1,2-benzisoxazoles. 4. General Procedures for the Transannulation of 1,2,3-Triazoles with 2,1-Benzisoxazoles and 1,2-Benzisoxazoles A 10 ml pressure tube, fitted with a rubber septum, was charged with triazole 1 (0.20 mmol, 1.0 equiv), Rh 2 (esp) 2 (2.3 mg, 0.003 mmol, 1.5mol %) and 1,2-benzisoxazole 2 (0.26 mmol, 1.3 6

equiv). The reaction vessel was added freshly distilled 1,2-DCE (1.0 ml), sealed with a teflon screwcap and then placed in an oil bath preheated to 160 C. The resulting solution was heated at this temperature for 5 min. After consumption of the triazole monitored by TLC analysis, the reaction was cooled to ambient temperature. DBU (1.5 equiv) was added to the reaction mixture, then the reaction mixture was allowed to stir for 30 min at room temperature. The solvent was removed in vacuo, and the resulting residue was submitted to flash chromatography (SiO 2, hexane/etoac) to obtain the corresponding quinazoline 3. A 10 ml pressure tube, fitted with a rubber septum, was charged with triazole 1 (0.20 mmol, 1.0 equiv), Rh 2 (esp) 2 (2.3 mg, 0.003 mmol, 1.5mol %) and 1,2-benzisoxazole 6 (0.6 mmol, 3.0 equiv). The reaction vessel was added freshly distilled 1,2-DCE (1.0 ml), sealed with a teflon screwcap and then placed in an oil bath preheated to 140 C. The resulting solution was heated at this temperature for 30 min. After consumption of the triazole monitored by TLC analysis, the reaction was cooled to ambient temperature. The solvent was removed in vacuo, and the resulting residue was submitted to flash chromatography (SiO 2, hexane/etoac) to obtain the corresponding imidazole 7. 5. Analysis Data of 2,1-Benzisoxazoles and 1,2-Benzisoxazoles Note: 2a, 2b, 2c, 2d and 6a are known compounds. 1 Thus, their 1 H-NMR, 13 C-NMR and GC-MS data are not provided. The 2,1-benzisoxazoles 2e, 2f, 2g and 6b, 6c are new compounds, and their spectroscopic data are provided below. 6-Fluoro-3-methylbenzo[c]isoxazole (2e): The product was obtained as a colorless solid (522 mg, 3.46 mmol, 78 %). mp 56-58 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 7.45 (dd, J = 9.2 Hz, J = 5.2 Hz, 1H), 7.05 (d, J = 9.2 Hz, 1H), 6.75 (t, 1 (a) Smalley, R. K.. Science of Synthesis, 2002. 11, 337-382.; (b) Bharate, S. B.; Padala, A. K.; Dar, B. A.; Yadav, R. R.; Singh, B.; Vishwakarm, R, A. Tetrahedron Lett. 2013, 54, 3558-3561. 7

J = 9.0 Hz, 1H), 2.78 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 166.6, 164.1 (d, J = 251.2 Hz), 157.4 (d, J = 13.2 Hz), 122.6 (d, J = 11.4 Hz), 162.2 (d, J = 30.7 Hz), 113.8, 97.3 (d, J = 24.9 Hz), 12.1; 19 F NMR (CDCl 3, 376 MHz): δ = -106.18 - -106.24 (m); HRMS m/z calcd for C 8 H 6 FNO [M+H] + : 152.0515; found: 152.0512. 6-Methoxy-3-methylbenzo[c]isoxazole (2f): The product was obtained as a colorless solid. (600 mg, 3.68 mmol, 75 %). mp 105-107 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 7.29 (d, J = 9.6 Hz, 1H), 6.61-6.60 (m, 2H), 3.86 (s, 3H), 2.71 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 164.9, 161.9, 158.6, 120.9, 120.0, 112.7, 89.5, 55.5, 11.9. HRMS m/z calcd for C 9 H 9 NO 2 [M+H] + : 164.0711; found: 164.0712. 4-Fluoro-3-methylbenzo[c]isoxazole (2g): The product was obtained as a colorless solid. (280 mg, 1.85 mmol, 75 %). mp 64-66 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 7.27 (d, J = 9.2 Hz, 1H), 7.19-7.14 (m, 1H), 6.50-6.46 (m, 1H), 2.89 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 165.4 (d, J = 6.5 Hz), 159.1 (d, J = 4.3 Hz), 155.7 (d, J = 256.9 Hz), 131.5 (d, J = 7.1 Hz), 111.3 (d, J = 5.3 Hz), 109.1 (d, J = 21.9 Hz), 104.7 (d, J = 17.3Hz), 13.3; 19 F NMR (CDCl 3, 376 MHz): δ = -119.44 - -119.48 (m); HRMS m/z calcd for C 8 H 7 FNO [M+H] + : 152.0511; found: 152.0512. 5-Methylbenzo[d]isoxazole (6b): The product was obtained as a colorless oil. (625 mg, 4.70 mmol, 94 %). 1 H NMR (CDCl 3, 400 MHz): δ = 8.61 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.8 Hz, 1H), 2.45 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 161.0, 146.0, 133.5, 131.7, 121.6, 121.2, 109.3, 21.1; HRMS m/z calcd for C 8 H 7 NO [M+H] + : 533.2102; found: 533.2110. 5-Chlorobenzo[d]isoxazole (6c): The product was obtained as a white solid. (1325 mg, 8.66mmol, 91 %). mp 61-63 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.67 (s, 1H), 7.71 (s, 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H); 13 C NMR (CDCl 3, 100 MHz): δ = 160.9, 145.8, 130.7, 129.5, 122.7, 121.4, 110.9; HRMS m/z calcd for C 7 H 4 ClNO [M+H] + : 507.1511; found: 507.1509. 8

6. Analysis Data of Quinazolines and Imidazoles Phenyl(4-(tosylmethyl)quinazolin-2-yl)methanone (3a): The product was obtained as a colorless solid. (10 mg, 0.025 mmol, 10 %). mp 165-167 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.38 (d, J = 8.4 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 8.03 (t, J = 7.8 Hz, 1H), 7.94 (d, J = 8.0 Hz, 2H), 7.83 (t, J = 7.6 Hz, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.46 (t, J = 7.8 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 5.15 (s, 2H), 2.29 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.1, 159.6, 157.9, 150.5, 145.6, 135.2, 135.2, 134.9, 133.7, 131.1, 130.0, 130.0, 129.9, 128.7, 128.4, 125.9, 124.5, 62.1, 21.7. HRMS m/z calcd for C 23 H 18 N 2 O 3 S [M+H] + : 403.1110; found: 403.1116. (4-Methylene-3-tosyl-1,2,3,4-tetrahydroquinazolin-2-yl)(phenyl)methanone (4a): The product was obtained as a colorless solid. (50 mg, 0.136 mmol, 57 %). mp 138-140 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.17 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 8.0 Hz, 2H), 7.60 (d, J = 7.2 Hz, 1H), 7.51 (t, J = 7.6 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 2H), 6.93 (t, J = 7.6 Hz, 1H), 6.60-6.56 (m, 2 H), 6.41 (d, J = 8.0 Hz, 1H), 5.50 (s, 1H), 5.13 (s, 1H), 4.60 (s, 1H), 2.24 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 193.9, 144.0, 140.8, 135.8, 134.8, 133.8, 133.3, 129.7, 129.4, 128.8, 128.7, 128.6, 124.3, 119.2, 116.3, 115.9, 109.9, 68.9, 21.5; HRMS m/z calcd for C 23 H 20 N 2 O 3 S [M+H] + : 405.1273; found: 405.1273. (4-Methylquinazolin-2-yl)(phenyl)methanone (5a): The product was obtained as a colorless solid. (34.0 mg, 0.137 mmol, 80 %). mp 78-79 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.20-8.12 (m, 4H), 7.95 (t, J = 7.4 Hz, 1H), 7.75 (t, J = 7.4 Hz, 1H), 7.61 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.4 Hz, 2H), 3.06 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.2, 169.5, 158.3, 149.1, 135.7, 134.4, 133.6, 131.2, 130.0, 129.1, 128.4, 125.2, 124.4, 22.1; HRMS m/z calcd for C 16 H 12 N 2 O [M+H] + : 249.1034; found: 249.1028. (4-Methylquinazolin-2-yl)(p-tolyl)methanone (5b): The product was obtained as a colorless solid. (39.0 mg, 0.149 mmol, 77 %). mp 109-111 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.18 (d, J = 8.4 Hz, 1H), 8.15 (d, J = 8.4 Hz, 1H), 8.03 (d, J = 8.4 Hz, 2H), 7.95 (t, J = 7.8 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 2H), 3.06 (s, 3H), 2.43 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.0, 169.5, 158.5, 149.1, 144.6, 134.4, 133.0, 9

131.4, 129.9, 129.2, 129.0, 125.2, 124.3, 22.2, 21.9; HRMS m/z calcd for C 17 H 14 N 2 O [M+H] + : 263.1185; found: 263.1184. (4-(tert- Butyl)phenyl)(4-methylquinazolin-2-yl)methanone (5c) The product was obtained as a colorless solid. (33.0 mg, 0.109 mmol, 52 %). mp 42-44 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.21 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.8 Hz, 2H), 7.98 (t, J = 7.6 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.52 (d, J = 8.4 Hz, 2H), 3.09 (s, 3H), 1.37 (s, 9H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.8, 169.5, 158.5, 157.4, 149.1, 134.3, 133.0, 131.2, 130.0, 129.0, 125.5, 125.2, 124.3, 35.3, 31.2, 22.1; HRMS m/z calcd for C 20 H 20 N 2 O [M+H] + : 305.1655; found: 305.1654. (4-Methoxyphenyl)(4-methylquinazolin-2-yl)methanone (5d): The product was obtained as a colorless solid. (40.0 mg, 0.144 mmol, 68 %). mp 143-145 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.18-8.12 (m, 4H), 7.94 (t, J = 7.2 Hz, 1H), 7.72 (t, J = 7.6 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 3.04 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.8, 169.5, 164.1, 158.7, 149.1, 134.3, 133.6, 129.9, 128.9, 128.5, 125.2, 124.2, 113.8, 55.6, 22.1; HRMS m/z calcd for C 17 H 14 N 2 O 2 [M+H] + : 279.1132; found: 279.1134. (4-Fluorophenyl)(4-methylquinazolin-2-yl)methanone (5e); The product was obtained as a colorless solid. (37.0 mg, 0.139 mmol, 68 %). mp 108-110 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.22-8.18 (m, 3H), 8.14 (d, J = 8.4 Hz, 1H), 7.96 (t, J = 7.6 Hz, 1H), 7.76 (t, J = 7.4 Hz, 1H), 7.15 (t, J = 8.6 Hz, 2H), 3.07 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.5, 169.7, 166.1 (d, J = 254.1 Hz), 157.9, 149.0, 134.5, 134.0 (d, J = 9.4 Hz), 132.0 (d, J = 2.8 Hz), 129.9, 129.3, 125.2, 124.3, 115.6 (d, J = 21.7 Hz), 22.1; 19 F NMR (CDCl 3, 376 MHz): δ = -104.26 - -104.33(m); HRMS m/z calcd for C 16 H 11 FN 2 O [M+H] + : 267.0937; found: 267.0934. (4-Chlorophenyl)(4-methylquinazolin-2-yl)methanone (5f). The product was obtained as a colorless solid. (43.0 mg, 0.152 mmol, 74 %). mp 118-120 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.20 (d, J = 8.4 Hz, 1H), 8.16-8.11 (m, 3H), 7.98 (t, J = 7.8 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 3.07 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.9, 169.8, 157.6, 149.0, 140.1, 134.6, 134.1, 132.7, 130.0, 10

129.4, 128.8, 125.3, 124.4, 21.2; HRMS m/z calcd for C 16 H 11 ClN 2 O [M+H] + : 283.0641; found: 283.0638. (4-Methylquinazolin-2-yl)(m-tolyl)methanone (5g). The product was obtained as a colorless solid. (37.0 mg, 0.141 mmol, 66 %). mp 100-102 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.18 (d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.97-7.92 (m, 2H), 7.88 (d, J = 7.6 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 3.05 (s, 3H), 2.40 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.5, 169.5, 158.3, 149.0, 138.2, 135.5, 134.4, 134.3, 131.4, 129.8, 129.0, 128.5, 128.2, 125.1, 124.2, 22.1, 21.4; HRMS m/z calcd for C 17 H 14 N 2 O [M+H] + : 263.1185; found: 263.1184. (3-Fluorophenyl)(4-methylquinazolin-2-yl)methanone (5h). The product was obtained as a colorless solid. (31.0 mg, 0.117 mmol, 54 %). mp 100-101 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.22 (d, J = 8.4 Hz, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.02-7.95 (m, 2H), 7.91 (d, J = 9.2 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.51-7.46 (m, 1H), 7.34 (t, J = 8.2 Hz, 1H), 3.09 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.8, 169.8, 162.6 (d, J = 245.6 Hz), 157.6, 149.1, 137.8 (d, J = 6.6 Hz), 134.5, 130.1, 130.0, 129.4, 127.1 (d, J = 3.0 Hz), 125.3, 124.4, 120.5 (d, J = 21.4 Hz), 117.9 (d, J = 22.7 Hz) 22.1; 19 F NMR (CDCl 3, 376 MHz): δ = -112.26 - -112.32 (m); HRMS m/z calcd for C 16 H 11 FN 2 O [M+H] + : 267.0935; found: 267.0934. (3-Chlorophenyl)(4-methylquinazolin-2-yl)methanone (5i). The product was obtained as a colorless solid. (32.0 mg, 0.113 mmol, 52 %). mp 75-77 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.21-8.15 (m, 3H), 8.04 (d, J = 7.6 Hz, 1H), 7.98 (t, J = 7.8 Hz, 1H), 7.78 (t, J = 7.4 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 3.07 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.8, 169.8, 157.4, 149.1, 137.3, 134.6, 134.6, 133.4, 131.2, 130.1, 129.7, 129.5, 129.4, 125.3, 124.5, 22.2; HRMS m/z calcd for C 16 H 12 ClN 2 O [M+H] + : 283.0641; found: 283.0638. (2-Fluorophenyl)(4-methylquinazolin-2-yl)methanone (5j): The product was obtained as a colorless solid. (27.0 mg, 0.098 mmol, 48 %). mp 104-106 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.19 (d, J = 8.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.97-7.93 (m, 2H), 7.76 (t, J = 7.6 Hz, 1H), 7.62-7.58 (m, 1H), 7.35-7.28 (m, 1H), 7.12 (t, J = 9.4 11

Hz, 1H), 3.06 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.3, 169.6, 161.9 (d, J = 253.6 Hz), 158.0, 149.4, 134.6 (d, J = 8.7 Hz), 134.3, 131.8 (d, J = 2.0 Hz), 130.2, 129.3, 126.0 (d, J = 12.5 Hz), 125.2, 124.5, 124.4 (d, J = 3.4 Hz), 116.3 (d, J = 21.9 Hz), 22.1; 19 F NMR (CDCl 3, 376 MHz): δ = -108.26 - -108.32 (m); HRMS m/z calcd for C 16 H 11 FN 2 O [M+H] + : 267.0932; found: 267.0934. (2-Chlorophenyl)(4-methylquinazolin-2-yl)methanone (5k): The product was obtained as a colorless solid. (24.0 mg, 0.085 mmol, 42 %). mp 115-116 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.18 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.4 Hz, 1H), 7.93 (t, J = 7.6 Hz, 1H), 7.78-7.71 (m, 2H), 7.50-7.40 (m, 3H), 3.05 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 194.0, 169.8, 157.0, 149.5, 138.0, 134.3, 133.0, 132.2, 131.1, 130.4, 130.0, 129.6, 126.9, 125.3, 124.5, 22.2; HRMS m/z calcd for C 16 H 11 ClN 2 O [M+H] + : 283.0638; found: 283.0638. (4-Methylquinazolin-2-yl)(o-tolyl)methanone (5l): The product was obtained as a colorless solid. (17.0 mg, 0.069 mmol, 35 %). mp 132-134 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.19 (d, J = 8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.95 (t, J = 7.6 Hz, 1H), 7.75 (t, J = 7.6 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 7.4 Hz, 1H), 7.31 (d, J = 7.6 Hz, 1H), 7.25 (t, J = 7.2 Hz, 1H), 3.06 (s, 3H), 2.51 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 195.4, 169.6, 158.6, 149.3, 139.7, 136.3, 134.3, 131.9, 131.8, 131.7, 130.2, 129.3, 125.3, 125.2, 124.3, 22.2, 21.4; HRMS m/z calcd for C 17 H 14 N 2 O [M+H] + : 263.1184; found:263.1184. (4-Methylquinazolin-2-yl)(naphthalen-1-yl)methanone (5m): The product was obtained as a colorless solid. (31.0 mg, 0.104 mmol, 59 %). mp 111-113 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.63 (s, 1H), 8.22 (t, J = 8.4 Hz, 2H), 8.17 (d, J = 8.4 Hz, 1H), 7.99-7.92 (m, 2H), 7.89 (t, J = 7.6 Hz, 2H), 7.76 (t, J = 7.8 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.52 (t, J = 7.4 Hz, 1H), 3.08 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.2, 169.6, 158.5, 149.1, 135.9, 134.4, 134.0, 133.0, 132.5, 130.0, 130.0, 129.1, 128.9, 128.3, 127.9, 126.7, 126.0, 125.2, 124.2, 22.2; HRMS m/z calcd for C 20 H 14 N 2 O [M+H] + : 299.1190; found: 299.1184. 12

(4-Methylquinazolin-2-yl)(thiophen-3-yl)methanone (5n): The product was obtained as a colorless solid. (27.0 mg, 0.106 mmol, 52 %). mp 65-66 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.75 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.97 (t, J = 7.6 Hz, 1H), 7.92 (d, J = 5.2 Hz, 1H), 7.76 (t, J = 7.6 Hz, 1H), 7.36-7.34 (m, 1H), 3.08 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 184.8, 169.6, 157.7, 149.3, 140.2, 137.3, 134.4, 130.1, 129.4, 129.3, 125.6, 125.2, 124.5, 22.2; HRMS m/z calcd for C 14 H 10 N 2 OS [M+H] + : 255.0593; found: 255.0592. (6-Chloro-4-methylquinazolin-2-yl)(phenyl)methanone (5o): The product was obtained as a colorless solid. (26.0 mg, 0.092 mmol, 57 %). mp 129-131 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.16 (s, 1H), 8.10 (d, J = 7.2 Hz, 3H), 7.89 (d, J = 8.8 Hz, 1H), 7.62 (t, J = 7.0 Hz, 1H), 7.49 (t, J = 7.4 Hz, 2H), 3.03 (s, 3H) ; 13 C NMR (CDCl 3, 100 MHz): δ = 191.8, 168.8, 158.4, 147.6, 135.5, 135.4, 135.0, 133.7, 131.7, 131.2, 128.4, 124.9, 124.3, 22.1; HRMS m/z calcd for C 16 H 11 ClN 2 O [M+H] + : 283.0637; found: 283.0638. (4,6-Dimethylquinazolin-2-yl)(phenyl)methanone (5p): The product was obtained as a colorless solid. (31.0 mg, 0.117 mmol, 60 %). mp 75-77 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.13 (d, J = 8.0 Hz, 2H), 8.04 (d, J = 8.4 Hz, 1H), 7.93 (s, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.60 (t, J = 7.4 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 3.03 (s, 3H), 2.62 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.3, 168.6, 157.5, 147.6, 139.7, 136.6, 135.8, 133.5, 131.3, 129.7, 128.4, 124.3, 124.1, 22.2, 22.1; HRMS m/z calcd for C 17 H 14 N 2 O [M+H] + : 263.1189; found: 263.1184. (7-Chloro-4-methylquinazolin-2-yl)(phenyl)methanone (5q): The product was obtained as a colorless solid. (36.0 mg, 0.128 mmol, 62 %). mp 129-131 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.14-8.09 (m, 4H), 7.69 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 7.4 Hz, 1H), 7.49 (t, J = 7.6 Hz, 2H), 3.04 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.9, 169.7, 159.2, 149.8, 140.7, 135.4, 133.7, 131.2, 130.2, 128.9, 128.5, 126.6, 122.7, 22.2; HRMS m/z calcd for C 16 H 11 ClN 2 O [M+H] + : 283.0640; found: 283.0638. (7-Fluoro-4-methylquinazolin-2-yl)(phenyl)methanone (5r): The product was obtained as a colorless solid. (45.0 mg, 0.168 mmol, 83 %). mp 92-94 o C; 1 H 13

NMR (CDCl 3, 400 MHz): δ = 8.22 (dd, J = 9.0 Hz, J = 5.8 Hz, 1H), 8.09 (d, J = 7.6 Hz, 2H), 7.75 (dd, J = 9.6 Hz, J = 2.0 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.53-7.46 (m, 3H), 3.04 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.0, 169.3, 165.9 (d, J = 255.6 Hz), 159.3, 151.1 (d, J = 13.7 Hz), 135.4, 133.7, 131.1, 128.5, 128.0 (d, J = 10.4 Hz), 121.6, 119.5 (d, J = 25.0 Hz), 113.7 (d, J = 20.4 Hz), 22.2; 19 F NMR (CDCl 3, 376 MHz): δ = -101.01-101.07 (m); HRMS m/z calcd for C 16 H 11 FN 2 O [M+H] + : 267.0940; found: 267.0934. (7-Methoxy-4-methylquinazolin-2-yl)(phenyl)methanone (5s): The product was obtained as a colorless solid. (39.0 mg, 0.139 mmol, 66 %). mp 88-89 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.11 (d, J = 7.6 Hz, 2H), 8.06 (d, J = 9.2 Hz, 1H), 7.61 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.2 Hz, 2H), 7.42 (s, 1H), 7.34 (d, J = 8.8 Hz, 1H), 3.97 (s, 3H), 2.99 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.4, 168.0, 164.4, 159.1, 151.9, 135.8, 133.5, 131.2, 128.4, 126.6, 122.2, 119.7, 107.4, 56.0, 21.9; HRMS m/z calcd for C 17 H 14 N 2 O 2 [M+H] + : 279.1137; found: 279.1134. (5-Fluoro-4-methylquinazolin-2-yl)(phenyl)methanone (5t): The product was obtained as a colorless solid. (32.0 mg, 0.12 mmol, 60 %). mp 98-100 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.12-8.09 (m, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.91-7.86 m, 1H), 7.62 (tt, J = 7.4 Hz, J = 1.2 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H), 7.42-7.37 (m, 1H), 3.17 (d, J = 6.0 Hz, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.8, 168.2 (d, J = 5.7 Hz), 159.0 (d, J =259.0 Hz), 158.6 (d, J = 2.0 Hz), 150.8, 135.3, 134.3 (d, J = 9.8 Hz), 133.8, 131.2, 128.5, 126.0 (d, J = 4.5 Hz), 115.5 (d, J = 13.4 Hz), 114.2 (d, J = 22.3 Hz), 26.8 (d, J = 9.1 Hz); 19 F NMR (CDCl 3, 376 MHz): δ = -107.12 - -107.21 (m); HRMS m/z calcd for C 16 H 12 FN 2 O [M+H] + : 267.0939; found: 267.0934. (6-Fluoro-4-methylquinazolin-2-yl)(4-fluorophenyl)methanone (5u): The product was obtained as a colorless solid. (42.0 mg, 0.147 mmol, 73 %). mp 128-129 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.24-8.21 (m, 1H), 8.17 (t, J = 7.2 Hz, 2H), 7.75 (d, J = 9.2 Hz, 1H), 7.52 (t, J = 8.6 Hz, 1H), 7.15 (t, J = 8.4 Hz, 2H), 3.04 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.3, 169.5, 167.4 (d, J = 26.6 Hz), 164.8 (d, J = 27.9 Hz), 159.0, 151.1 (d, J = 13.6 Hz), 134.0 (d, J = 9.4 Hz), 131.8 (d, J = 2.9 Hz), 128.0 (d, J = 10.4 Hz), 121.6, 119.7 (d, J = 29.1 Hz), 115.7 (d, J = 21.8 Hz), 113.7 (d, J = 10.2 Hz), 22.2; 19 F NMR 14

(CDCl 3, 376 MHz): δ = -100.82 - -100.88 (m), -103.88 - -103.96 (m); HRMS m/z calcd for C 16 H 10 F 2 N 2 O [M+H] + : 285.0838; found: 285.0839. (6-Chloro-4-methylquinazolin-2-yl)(4-chlorophenyl)methanone (5v): The product was obtained as a colorless solid. (36.0 mg, 0.113 mmol, 55 %). mp 167-168 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.16 (s, 1H), 8.10 (d, J = 8.4 Hz, 3H), 7.90 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 8.4 Hz, 2H), 3.04 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.5, 169.0, 157.8, 147.6, 140.3, 135.5, 135.3, 133.9, 132.6, 131.7, 128.8, 125.0, 124.3, 22.2; HRMS m/z calcd for C 16 H 10 Cl 2 N 2 O [M+H] + : 317.0252; found: 317.0248. (4,6-Dimethylquinazolin-2-yl)(p-tolyl)methanone (5w): The product was obtained as a colorless solid. (32.0 mg, 0.116 mmol, 62 %). mp 106-108 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.06 (d, J = 8.4 Hz, 3H), 7.95 (s, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 3.04 (s, 3H), 2.64 (s, 3H), 2.45 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.0, 168.5, 157.8, 147.6, 144.4, 139.5, 136.5, 133.3, 131.4, 129.6, 129.1, 124.3, 124.0, 22.2, 22.1, 21.9. HRMS m/z calcd for C 18 H 16 N 2 O [M+H] + : 277.1341; found: 277.1341. (6-Methoxy-4-methylquinazolin-2-yl)(4-methoxyphenyl)methanone (5x): The product was obtained as a colorless solid. (36.0 mg, 0.117 mmol, 55 %). mp 129-131 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.12 (d, J = 8.4 Hz, 2H), 8.06 (d, J = 8.8 Hz, 1H), 7.42 (s, 1H), 7.33 (d, J = 9.2 Hz, 1H), 6.96 (d, J = 8.0 Hz, 2H), 3.97 (s, 3H), 3.88 (s, 3H),2.98 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.0, 168.0, 164.4, 164.1, 159.5, 151.8, 133.7, 128.6, 126.6, 122.0, 119.6, 113.8, 107.4, 56.0, 55.7, 21.9; HRMS m/z calcd for C 18 H 16 N 2 O 3 [M+H] + : 309.1240; found: 309.1239. (6-Chloro-4-methylquinazolin-2-yl)(p-tolyl)methanone (5y): The product was obtained as a colorless solid. (36.0 mg, 0.121 mmol, 58 %). mp 175-177 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.16 (s, 1H), 8.10 (d, J = 8.8 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.88 (d, J = 9.2 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 3.03 (s, 3H), 2.44 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.5, 168.7, 158.7, 147.7, 144.7, 135.3, 134.8, 132.9, 131.7, 131.3, 129.2, 124.9, 124.3, 22.1, 22.0; HRMS m/z calcd for C 17 H 13 ClN 2 O [M+H] + : 297.0796; found: 297.0795. 15

(7-Fluoro-4-methylquinazolin-2-yl)(thiophen-3-yl)methanone (5z): The product was obtained as a colorless solid. (41.0 mg, 0.152 mmol, 75 %). mp 86-88 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.70 (d, J = 2.8 Hz, 1H), 8.22 (dd, J = 9.2 Hz, J = 5.6 Hz, 1H ), 7.89 (d, J = 4.8 Hz, 1H), 7.80 (dd, J = 9.8 Hz, J = 2.4 Hz, 1H), 7.52 (td, J = 7.8 Hz, J = 2.4 Hz, J = 2.4 Hz, 1H), 7.37-7.35 (m, 1H), 3.06 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 184.5, 169.4, 165.9 (d, J = 255.7 Hz), 158.5, 151.2 (d, J = 13.6 Hz), 139.9, 137.5, 129.3, 128.0 (d, J = 10.4 Hz), 125.7, 121.7, 119.8 (d, J = 25.0 Hz), 113.8 (d, J = 20.4 Hz), 22.3; 19 F NMR (CDCl 3, 376 MHz): δ = -101.01 - -101.07 (m); HRMS m/z calcd for C 14 H 9 FN 2 O[M+H] + : 273.0501; found: 273.0498. (7-Fluoro-4-methylquinazolin-2-yl)(naphthalen-1-yl)methanone (5aa): The product was obtained as a colorless solid. (41.0 mg, 0.129 mmol, 64 %). mp 160-161 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.59 (s, 1H), 8.25 (dd, J = 9.2 Hz, J = 6.0 Hz, 1H ), 8.20 (d, J = 8.8 Hz, 1H), 7.94 (d, J = 8.8 Hz, 1H), 7.92-7.88 (m, 2H), 7.79 (dd, J = 9.4 Hz, J = 2.2 Hz, 1H), 7.61 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 3.07 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 192.0, 169.4, 166.0 (d, J = 255.8 Hz), 159.5, 151.2 (d, J = 13.2 Hz), 136.0, 134.0, 132.8, 132.5, 130.0, 129.0, 128.4, 128.1 (d, J = 10.4 Hz), 127.9, 126.8, 125.8, 121.7 (d, J = 1.2 Hz), 119.6 (d, J = 25.0 Hz), 113.8 (d, J = 20.4 Hz), 22.3; 19 F NMR (CDCl 3, 376 MHz): δ = -101.00 - -101.06 (m); HRMS m/z calcd for C 20 H 13 FN 2 O[M+H] + : 317.1097; found: 317.1090. 2-(4-Phenyl-1-tosyl-1H-imidazol-2-yl)phenol (7a): The product was obtained as a white solid. (72.0 mg, 0.185 mmol, 91 %). mp 49-51 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 10.23 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.97 (s, 1H), 7.83 (d, J = 7.2 Hz, 2H), 7.48-7.43 (m, 4H), 7.39-7.34 (m, 2H), 7.17 (d, J = 8.0 Hz, 2H), 7.00-6.97 (m, 2H), 2.36 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 156.7, 147.5, 146.4, 139.8, 134.1, 132.1, 131.2, 130.5, 130.1, 128.9, 128.5, 127.4, 125.4, 118.8, 116.9, 116.4, 113.2, 21.8; HRMS m/z calcd for C 22 H 18 N 2 O 3 S [M+H] + : 391.1107; found: 391.1116. 2-(4-(P-tolyl)-1-tosyl-1H-imidazol-2-yl)phenol (7b): The product was obtained as a white solid. (77.0 mg, 0.191 mmol, 96 %). mp 123-125 o C; 1 H NMR (CDCl 3, 16

400 MHz): δ = 10.48 (s, 1H), 8.05 (d, J = 7.6 Hz, 1H), 7.93 (s, 1H), 7.72 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.36 (t, J = 7.8 Hz, 1H), 7.26 (d, J = 7.6 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.98 (t, J = 7.6 Hz, 2H), 2.41 (s, 3H), 2.36 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 156.8, 147.5, 146.3, 139.9, 138.5, 134.3, 132.0, 130.5, 130.1, 129.6, 128.5, 127.4, 125.3, 118.8, 116.9, 116.0, 113.2, 21.8, 21.4; HRMS m/z calcd for C 23 H 20 N 2 O 3 S [M+H] + : 405.1269; found: 405.1273. 2-(4-(4-Chlorophenyl)-1-tosyl-1H-imidazol-2-yl)phenol (7c): The product was obtained as a white solid. (76.0 mg, 0.179 mmol, 93 %). mp 128-130 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 10.14 (s, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.93 (s, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.33 (t, J = 7.8 Hz, 1H), 7.14 (d, J = 8.0 Hz, 2H), 6.97-6.94 (m, 2H), 2.33 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 156.0, 147.5, 146.5, 138.8, 134.2, 134.1, 132.2, 130.5, 130.1, 129.9, 129.1, 127.5, 126.6, 118.9, 116.9, 116.6, 113.2, 21.8; HRMS m/z calcd for C 22 H 17 ClN 2 O 3 S [M+H] + : 425.0720; found: 425.0727. 2-(1-Tosyl-4-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)phenol (7d): The product was obtained as a white solid. (72.0 mg, 0.157 mmol, 81 %). mp 112-114 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 10.03 (s, 1H), 8.04 (s, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.90 (d, J =8.0 Hz, 2H), 7.67 (d, J =8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.35 (t, J = 7.6 Hz, 1H), 7.15 (d, J = 8.0 Hz, 2H), 6.99-6.95 (m, 2H), 2.34 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 156.6, 147.7, 146.7, 138.5, 134.8, 134.0, 132.3, 130.6, 130.2 (q, J = 32.4 Hz), 130.2, 127.6, 125.9 (q, J = 3.7 Hz), 125.6, 124.2 (q, J = 270.4 Hz), 119.0, 117.7, 117.0, 113.1, 21.8; 19 F NMR (CDCl 3, 376 MHz): δ = -62.61 (s);hrms m/z calcd for C 23 H 17 F 3 N 2 O 3 S [M+H] + : 459.0981; found: 459.0990. 4-Methyl-2-(4-phenyl-1-tosyl-1H-imidazol-2-yl)phenol (7e): The product was obtained as a white solid. (73.0 mg, 0.181 mmol, 88 %). mp 118-120 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 9.99 (s, 1H), 7.86 (s, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.65 (s, 1H), 7.38-7.31 (m, 4H), 7.25 (t, J = 7.2 Hz, 1H), 7.07-7.02 (m, 3H), 6.77 (d, J = 8.0 Hz, 2H), 2.25 (s, 3H), 2.24 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 154.5, 147.6, 146.4, 139.8, 134.4, 132.7, 131.4, 130.5, 130.0, 128.9, 128.5, 127.8, 127.5, 125.4, 116.7, 116.3, 112.9, 21.8, 20.6; HRMS m/z calcd for C 23 H 20 N 2 O 3 S [M+H] + : 405.1271; found: 405.1273. 17

4-Chloro-2-(4-phenyl-1-tosyl-1H-imidazol-2-yl)phenol (7f): The product was obtained as a colorless solid. (76.0 mg, 0.179 mmol, 92 %). mp 119-121 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 10.86 (s, 1H), 8.01 (s, 1H), 8.00 (s, 1H), 7.79 (d, J = 7.6 Hz, 2H), 7.58 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 7.4 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.25-7.22 (m, 3H), 6.90 (d, J = 8.8 Hz, 1H), 2.37 (s, 3H); 13 C NMR (CD 3 OD, 100 MHz): δ = 155.6, 146.8, 145.9, 139.6, 134.0, 131.6, 131.0, 130.2, 129.3, 129.0, 128.7, 127.8, 125.4, 123.6, 118.5, 116.8, 113.9, 21.8; HRMS m/z calcd for C 22 H 17 ClN 2 O 3 S [M+H] + : 425.0714; found: 425.0717. (7-chloro-4-methylene-3-(phenylsulfonyl)-1,2,3,4-tetrahydroquinazolin-2 -yl)(phenyl)methanone (4b): The product was obtained as a colorless solid. (50.0 mg, 0.118 mmol, 57 %). mp 153-155 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.16 (d, J = 7.6 Hz, 2H), 7.76 (d, J = 7.6 Hz, 2H), 7.63 (t, J = 7.4 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.27-7.23 (m, 2H), 7.05 (d, J = 8.4 Hz, 1H), 6.59 (s, 1H), 6.54 (dd, J = 8.6 Hz, J = 1.8 Hz, 1H), 6.41 (d, J = 2.0 Hz, 1H), 5.50 (s, 1H), 5.17 (s, 1H), 4.63 (s, 1H); 13 C NMR (CDCl 3, 100 MHz): δ = 193.3, 141.7, 137.5, 135.4, 134.8, 134.1, 133.4, 132.9, 129.5, 128.9, 128.6, 128.3, 125.6, 119.6, 115.3, 114.7, 110.9, 68.6; HRMS m/z calcd for C 22 H 18 N 2 O 3 ClS [M+H] + : 425.0728; found: 425.0727. (7-chloro-4-((phenylsulfonyl)methyl)quinazolin-2-yl)(phenyl)methanone (3b): The product was obtained as a colorless solid. (13.0 mg, 0.031 mmol, 15 %). mp 203-205 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.35 (d, J = 9.2Hz, 1H), 8.20 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.79 (dd, J = 9.0 Hz, J = 2.0 Hz, 1H), 7.68 (d, J = 7.2 Hz, 2H), 7.63 (t, J = 7.2 Hz, 1H), 7.58 (t, J = 7.4 Hz, 1H), 7.49-7.41 (m, 4H),5.14 (s, 2H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.8, 159.7, 158.9, 151.2, 141.9, 137.8, 135.0, 134.6, 133.9, 131.2, 131.1, 129.4, 128.9, 128.7, 128.5, 127.4, 122.9, 62.2; HRMS m/z calcd for C 22 H 16 N 2 O 3 ClS [M+H] + : 423.0563; found: 423.0570. (7-chloro-4-(tosylmethyl)quinazolin-2-yl)(phenyl)methanone (3ba): The product was obtained as a colorless solid. (2.6 mg, 0.006 mmol, 8.2 %). mp 194-196 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.35 (d, J = 9.2Hz, 1H), 8.20 18

(d, J = 2.0 Hz, 1H), 7.92 (d, J = 8.4 Hz, 2H), 7.78 (dd, J = 8.8 Hz, J = 2.0 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.52 (d, J = 8.0 Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.19 (d, J = 2.0 Hz, 2H), 5.12 (s, 2H), 2.30 (s, 3H); 13 C NMR (CDCl 3, 100 MHz): δ = 190.8, 159.9, 158.9, 151.1, 145.8, 141.9, 135.0, 134.7, 133.9, 131.1, 131.0, 130.0, 128.9, 128.7, 128.5, 127.5, 122.9, 62.3, 21.7; HRMS m/z calcd for C 23 H 18 N 2 O 3 ClS [M+H] + : 437.0720; found: 437.0727. phenyl(4-((phenylsulfonyl)methyl)quinazolin-2-yl)methanone (3ab): The product was obtained as a colorless solid. (2.3 mg, 0.006 mmol, 8.4 %). mp 129-131 o C; 1 H NMR (CDCl 3, 400 MHz): δ = 8.38 (d, J = 8.4Hz, 1H), 8.22 (d, J = 8.4 Hz, 1H), 8.05 (t, J = 7.6 Hz, 1H), 7.94 (d, J = 7.6 Hz, 2H), 7.85 (t, J = 7.8 Hz, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.56 (t, J = 7.4 Hz, 1H), 7.49-7.40 (m, 4H), 5.18 (s, 2H); 13 C NMR (CDCl 3, 100 MHz): δ = 191.6, 159.9, 158.4, 151.0, 138.4, 135.8, 135.7, 134.9, 134.2, 131.6, 130.6, 130.5, 129.8, 128.9, 129.1, 126.3, 124.9, 62.5; HRMS m/z calcd for C 22 H 17 N 2 O 3 S [M+H] + : 389.0955; found: 389.0960. 19

7. NMR Spectra of 2,1-Benzsoxazoles and 1,2-Benzisoxazoles 1 H NMR Spectrum for 2e (CDCl 3, 400 MHz) 13 C NMR Spectrum for 2e (CDCl 3, 100 MHz) 20

19 F NMR Spectrum for 2e (CDCl 3, 376 MHz) 1 H NMR Spectrum for 2f (CDCl 3, 400 MHz) 21

13 C NMR Spectrum for 2f (CDCl 3, 100 MHz) 1 H NMR Spectrum for 2g (CDCl 3, 400 MHz) 22

13 C NMR Spectrum for 2g (CDCl 3, 100 MHz) 19 F NMR Spectrum for 2g (CDCl 3, 376 MHz) 23

1 H NMR Spectrum for 6b (CDCl 3, 400 MHz) 13 C NMR Spectrum for 6b (CDCl 3, 100 MHz) 24

1 H NMR Spectrum for 6c (CDCl 3, 400 MHz) 13 C NMR Spectrum for 6c (CDCl 3, 100 MHz) 25

8. NMR Spectra of Quinazolines and Imidazoles 1 H NMR Spectrum for 3a (CDCl 3, 400 MHz) 13 C NMR Spectrum for 3a (CDCl 3, 100 MHz) 26

1 H NMR Spectrum for 4a (CDCl 3, 400 MHz) 13 C NMR Spectrum for 4a (CDCl 3, 100 MHz) 27

1 H NMR Spectrum for 5a (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5a (CDCl 3, 100 MHz) 28

1 H NMR Spectrum for 5b (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5b (CDCl 3, 100 MHz) 29

1 H NMR Spectrum for 5c (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5c (CDCl 3, 100 MHz) 30

1 H NMR Spectrum for 5d (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5d (CDCl 3, 100 MHz) 31

1 H NMR Spectrum for 5e (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5e (CDCl 3, 100 MHz) 32

19 F NMR Spectrum for 5e (CDCl 3, 376 MHz) 1 H NMR Spectrum for 5f (CDCl 3, 400 MHz) 33

13 C NMR Spectrum for 5f (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5g (CDCl 3, 400 MHz) 34

13 C NMR Spectrum for 5g (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5h (CDCl 3, 400 MHz) 35

13 C NMR Spectrum for 5h (CDCl 3, 100 MHz) 19 F NMR Spectrum for 5h (CDCl 3, 376 MHz) 36

1 H NMR Spectrum for 5i (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5i (CDCl 3, 100 MHz) 37

1 H NMR Spectrum for 5j (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5j (CDCl 3, 100 MHz) 38

19 F NMR Spectrum for 5h (CDCl 3, 376 MHz) 1 H NMR Spectrum for 5k (CDCl 3, 400 MHz) 39

13 C NMR Spectrum for 5k (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5l (CDCl 3, 400 MHz) 40

13 C NMR Spectrum for 5l (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5m (CDCl 3, 400 MHz) 41

13 C NMR Spectrum for 5m (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5n (CDCl 3, 400 MHz) 42

13 C NMR Spectrum for 5n (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5o (CDCl 3, 400 MHz) 43

13 C NMR Spectrum for 5o (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5p (CDCl 3, 400 MHz) 44

13 C NMR Spectrum for 5p (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5q (CDCl 3, 400 MHz) 45

13 C NMR Spectrum for 5q (CDCl 3, 100 MHz) 1 H NMR Spectrum for 5r (CDCl 3, 400 MHz) 46

13 C NMR Spectrum for 5r (CDCl 3, 100 MHz) 19 F NMR Spectrum for 5r (CDCl 3, 376 MHz) 47

1 H NMR Spectrum for 5s (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5s (CDCl 3, 100 MHz) 48

1 H NMR Spectrum for 5t (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5t (CDCl 3, 100 MHz) 49

19 F NMR Spectrum for 5t (CDCl 3, 376 MHz) 1 H NMR Spectrum for 5u (CDCl 3, 400 MHz) 50

13 C NMR Spectrum for 5u (CDCl 3, 100 MHz) 19 F NMR Spectrum for 5u (CDCl 3, 376 MHz) 51

1 H NMR Spectrum for 5v (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5v (CDCl 3, 100 MHz) 52

1 H NMR Spectrum for 5w (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5w (CDCl 3, 100 MHz) 53

1 H NMR Spectrum for 5x (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5x (CDCl 3, 100 MHz) 54

1 H NMR Spectrum for 5y (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5y (CDCl 3, 100 MHz) 55

1 H NMR Spectrum for 5z (CDCl 3, 400 MHz) 13 C NMR Spectrum for 5z (CDCl 3, 100 MHz) 56

19 F NMR Spectrum for 5z (CDCl 3, 376 MHz) 1 H NMR Spectrum for 5aa (CDCl 3, 400 MHz) 57

13 C NMR Spectrum for 5aa (CDCl 3, 100 MHz) 19 F NMR Spectrum for 5aa (CDCl 3, 376 MHz) 58

1 H NMR Spectrum for 7a (CDCl 3, 400 MHz) 13 C NMR Spectrum for 7a (CDCl 3, 100 MHz) 59

1 H NMR Spectrum for 7b (CDCl 3, 400 MHz) 13 C NMR Spectrum for 7b (CDCl 3, 100 MHz) 60

1 H NMR Spectrum for 7c (CDCl 3, 400 MHz) 13 C NMR Spectrum for 7c (CDCl 3, 100 MHz) 61

1 H NMR Spectrum for 7d (CDCl 3, 400 MHz) 13 C NMR Spectrum for 7d (CDCl 3, 100 MHz) 62

19 F NMR Spectrum for 7d (CDCl 3, 376 MHz) 1 H NMR Spectrum for 7e (CDCl 3, 400 MHz) 63

13 C NMR Spectrum for 7e (CDCl 3, 100 MHz) 1 H NMR Spectrum for 7f (CDCl 3, 400 MHz) 64

13 C NMR Spectrum for 7f (CDCl 3, 100 MHz) 1 H NMR Spectrum for4b (CDCl 3, 400 MHz) 65

13 C NMR Spectrum for 4b (CDCl 3, 100 MHz) 1 H NMR Spectrum for 3b (CDCl 3, 400 MHz) 66

13 C NMR Spectrum for 3b (CDCl 3, 100 MHz) 1 H NMR Spectrum for 3ba (CDCl 3, 400 MHz) 67

13 C NMR Spectrum for 3ba (CDCl 3, 100 MHz) 1 H NMR Spectrum for 3ab (CDCl 3, 400 MHz) 68

13 C NMR Spectrum for 3ab (CDCl 3, 100 MHz) 69

9. X-ray Crystallographic Structure of 3a and 5f X-ray crystallographic structure and data of 3a Compound formula 3a C 23 H 18 N 2 O 3 S FW 402.10 crystal system monoclinic space group P 1 21/c 1 a/å 9.8125(11) b/å 10.1752(9) c/å 10.3110(9) /deg 77.841(8) /deg 83.921(8) /deg 71.108(9) V/Å 3 951.40(17) Z 2 D c /g cm -3 1.405 /mm -1 0.199 R a 1 (I 2 ) 0.0589(2698) wr b 2 (all data) 0.1419(4287) GOF 1.051 70

X-ray crystallographic structure and data of 5f Compound formula 5f C 18 H 13 Cl N 2 O FW 282.72 crystal system monoclinic space group P 1 21/c 1 a/å 12.766(3) b/å 16.060(3) c/å 6.7465(13) /deg 90 /deg 98.818(16) /deg 90 V/Å 3 1366.8(5) Z 4 D c /g cm -3 1.374 /mm -1 0.275 R a 1 (I 2 ) 0.0695(1268) wr b 2 (all data) 0.1884(2671) GOF 0.991 71