Palladium-Catalyzed Decarboxylative Synthesis of Arylamines

Transcription

1 Palladium-Catalyzed Decarboxylative Synthesis of Arylamines Qipu Dai *, Peihe Li, Nuannuan Ma and Changwen Hu* Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic, School of Chemistry, Beijing Institute of Technology, Beijing , People s Republic of China daiqipu@bit.edu.cn,cwhu@bit.edu.cn. Supporting Information Table of Contents General methods S-2 Procedures for the Preparation of Starting Materials S-2 Procedures for the Preparation of Products S-3 Mechanism Procedure for the Synthesis of Carbazoles S-5 S-10 Characterization data S-11 NMR spectra S-22 S-1

2 General methods. All commercially available reagents were used without further purification. Unless stated otherwise, all reactions were carried out in Schlenk Tube under a dry argon or nitrogen atmosphere. All solvents were purified and dried according to standard methods prior to use. Column chromatography was performed on silica gel ( mesh). 1 H NMR spectra were recorded on a 400 MHz NMR spectrometer. Chemical shifts were quoted in parts per million (ppm) referenced to the appropriate solvent peak or 0.0 ppm for tetramethylsilane. The following abbreviations were used to describe peak splitting patterns when appropriate: br = broad, s = singlet, d = doublet, t = triplet, q = quartet, sep = septet, dd = doublet of doublet, td = triplet of doublet, ddd = doublet of doublet of doublet, m = multiplet. Coupling constants, J, were reported in hertz unit (Hz). 13 C NMR spectra were recorded on a 101 MHz NMR spectrometer. Chemical shifts were reported in ppm referenced to the center of a triplet at 77.0 ppm of chloroform-d. IR spectra were recorded on a FT-IR spectrometer. Melting points were determined using an X-4 apparatus and are uncorrected. GC-MS data were performed on Agilent 7890A. GC analyses were performed on a Shimadzu GC-2014 equipped with a capillary column (HP-5 30 m 0.25 μm) using a flame ionization detector. Elemental analyses were obtained on a EuroEA3000 elemental analyzer. 2. Procedures for the Preparation of Starting Materials 2.1. Representative procedure for the synthesis of O-aroyloxycarbamates To a 250 ml flame-dried round bottom flask equipped with a stir bar, an N-hydroxyl carbamate S1 (20 mmol, 1.0 equiv), 2-methylbenzoic acid (2.86 g, 21 mmol) and anhydrous CH2Cl2 (80 ml) were added. The flask was cooled to -15 C. DCC (4.53 g, 22 mmol, dissolved in 20 ml of anhydrous CH2Cl2) solution was then added dropwise. The reaction mixture was stirred at the same temperature for additional 30 min until the N-hydroxyl carbamate was fully consumed (monitored by TLC). The white precipitate (N,N-dicyclohexylurea) was removed by S-2

3 filtration and the filtrate was concentrated in vacuo and dissolved again in Et2O (30 ml). The solution was cooled to -20 o C for 2 h and filtered again to remove additional precipitate. The organic layer was then concentrated in vacuo and the residue was recrystallized from hexanes and EtOAc to afford corresponding acyloxyl carbamate 2 as a white solid (yield 86%). Lu, D.-F.; Zhu, C.-L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, N-hydroxyl tert-butyl carbamate S1a was prepared from hydroxylamine hydrochloride with (Boc)2O, according to a known procedure. A suspension of NH2OH HCl (9.6 g, 0.14 mol, 1.5 equiv) and K2CO3 (7.2 g, 0.07 mol, 1.5 equiv) in Et2O (60 ml) and H2O (2 ml) was stirred for about 1 h at room temperature with evolution of CO2 gas. A solution of Boc2O (20.0 g, 92 mmol) in Et2O (40 ml) was then added dropwise at 0 C and the suspension was stirred at room temperature for 12 h. The organic phase was decanted and the solid was washed with Et2O (30 ml 2) and the organic layers were combined and concentrated. Recrystallization with a cyclohexane/toluene mixture afforded the desired product S1a. Lu, D.-F.; Zhu, C.-L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, N-hydroxyl carbamates were prepared from hydroxylamine with the corresponding chloroformates according to a known procedure. Hydroxylamine hydrochloride (13.9 g, 200 mmol) was added to aqueous solution of NaOH (1.5 M, 160 ml, 240 mmol). The solution was cooled to 0 C and chloroformate (38 mmol) was added dropwise. Upon the completion of addition, the mixture was warmed up to room temperature and stirred for additional 2 h. The reaction was then acidified with aqueous HCl (6 M) till ph is around 4.5. Then the mixture was extracted with Et2O (200 ml 3) and the combined organic layers were washed with brine and dried over anhydrous Na2SO4. After removal of the solvent in vacuo, the N-hydroxyl carbamate S-3

4 was used directly without further purification. Lu, D.-F.; Zhu, C.-L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, Procedure for the preparation of N-hydroxyl carbamate (S1e-g): To a flame-dried 100 ml round bottom flask equipped with a stir bar was added CDI (1.78 g, 11 mmol) in anhydrous THF (30 ml). The flask was cooled to 0 C and alcohol (10 mmol) was added dropwise. The mixture was stirred for additional 1 h at room temperature and then NH2OH HCl (1.04 g, 15 mmol) and imidazole (0.82 g, 12 mmol) were added in one portion. The reaction was monitored by TLC, until the starting material disappeared (about 1 h). Then the mixture was filtered and concentrated in vacuo. The residue was dissolved in EtOAc (40 ml) and washed with aqueous HCl (1 M, 20 ml 3). The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the crude product S1e-g (85-88% yield), which can be used directly for next step. Lu, D.-F.; Zhu, C.-L.; Jia, Z.-X.; Xu, H. J. Am. Chem. Soc. 2014, 136, Procedures for the Preparation of Products 3.1 Representative procedure for aroyloxycarbamates decarboxylative reaction (in situ) (Table 2, entry 1): To a solution of 1a (0.126 g, 0.5 mmol), PdCl2(PPh3)2 ( g, mmol, 5 mol%) and Cs2CO3 ( g, 1.0 mmol) in chlorobenzene (5 ml) in a Schlenk Pressure Tube (10 ml) under a dry argon atmosphere. The reaction mixture was vigorously stirred at 85 o C for 1.0 h, quenched by ethyl acetate, and purified by flash chromatography (hexanes) to give 2a (0.089 g, 86%). S-4

5 To a solution of benzoic acid ( g, mmol) and tert-butyl hydroxycarbamate (0.067 g, 0.5 mmol) in chlorobenzene (3 ml) at -15 C was added DCC ( g, 0.55 mmol dissolved in 3 ml of chlorobenzene) solution was then added dropwise. After the reaction mixture was stirred at the same temperature for 0.5 h until the N-hydroxyl carbamate was fully consumed (monitored by TLC). Then was added PdCl2(PPh3)2 ( g, mmol, 5 mol%) and Cs2CO3 ( g, 1.0 mmol). The reaction mixture was vigorously stirred at 85 o C for 1.0 h, extracted by ethyl acetate, and purified by flash chromatography (hexanes) to give 2a (0.086 g, 83%). Mechanism Experiment: S-5

6 1b and 1b: 13 C NMR (101 MHz, CDCl3) To a 100 ml flame-dried round bottom flask equipped with a stir bar, an tert-butyl hydroxycarbamate S1 (2 mmol, g, 1.0 equiv), benzoic acid or 13 C-labelled benzoic acid (0.256 g, 2.1 mmol) and anhydrous CH2Cl2 (10 ml) were added. The flask was cooled to -15 C. DCC (0.453 g, 22 mmol, dissolved in 10 ml of anhydrous CH2Cl2) solution was then added dropwise. The reaction mixture was stirred at the same temperature for additional 30 min until the tert-butyl hydroxycarbamate was fully consumed (monitored by TLC). The white precipitate (N,N -dicyclohexylurea) was removed by filtration and the filtrate was concentrated in vacuo and dissolved again in Et2O (10 ml). The solution was cooled to -20 o C for 2 h and filtered again to remove additional precipitate. The organic layer was then concentrated in vacuo and the residue was recrystallized from hexanes and EtOAc to afford corresponding acyloxyl carbamate 1b or 1b as a white solid (yield 82%). 1b: 13 C NMR (101 MHz, CDCl3): δ 166.1, 155.5, 134.1, 129.9, 128.7, 126.9, 83.4, C-labelled 1b : 13 C NMR (101 MHz, CDCl3): δ166.1, 155.5, 134.1, (d, J = 2.5 Hz), (d, J = 4.7 Hz), (d, J = 75.8 Hz), 83.4, S-6

7 2b and 2b: 13 C NMR (101 MHz, CDCl3) To a solution of 1b or 1b (0.119 g, 0.5 mmol), PdCl2(PPh3)2 ( g, mmol, 5 mol%) and Cs2CO3 ( g, 0.5 mmol) in chlorobenzene (5 ml) in a Schlenk Pressure Tube (10 ml) under a dry argon atmosphere. The reaction mixture was vigorously stirred at 120 o C for 2.5 h, quenched by ethyl acetate, and purified by flash chromatography (hexanes) to give 2b or 2b (0.043 g, 45%). 2b: 13 C NMR (101 MHz, CDCl3): δ 152.8, 138.3, 128.9, 122.9, 118.5, 80.4, b : 13 C NMR (101 MHz, CDCl3): δ 152.8, 138.3, 128.9, 122.9, 118.5, 80.4, S-7

8 GC Report: Entry Catalyst Cs2CO3 O2 N2 CO2 1(Air) No No Y Y No 2(CO2) No No Y Y Y 3 Y Y Y Y Y 4 N Y Y Y No (As in the progress of analysis, it can hardly expel air completely, so there is always some air in the sample.) From the report, we can conclude that CO2 was produced. Proedure: To a solution of 1a (0.126 g, 0.5 mmol), PdCl2(PPh3)2 ( g, mmol, 5 mol%) and Cs2CO3 ( g, 0.5 mmol) in chlorobenzene (5 ml) in a Schlenk Pressure Tube (10 ml) under a dry argon atmosphere (degassed by Argon for three times). After cooling down to room temperature, the reaction gas was detected by GC. S-8

9 GC Report: S-9

10 General Procedure for the Synthesis of Carbazoles: To a solution of 1h (3.133 g, 10 mmol), PdCl2(PPh3)2 (0.350 g, 0.05 mmol, 5 mol%) and Cs2CO3 (3.258 g, 10 mmol) in chlorobenzene (50 ml) in a Schlenk Pressure Tube (100 ml) under a dry argon atmosphere. The reaction mixture was vigorously stirred at 85 o C for 1.5 h, quenched by ethyl acetate, and purified by flash chromatography (hexanes) to give 2h (2.366 g, 88%). General Procedure for the Synthesis of Carbazoles (from 2h to 3h and 4h): To a solution of Pd(OAc)2 (17.92 mg, mmol. 20 mol%), 4Å molecular sieve powder (160.5 mg,150 wt %), along with 107 mg (0.4 mmol) substrate 2h in DMSO : toluene (1 ml: 1 ml) in a Schlenk Pressure Tube (10 ml) under a dry oxygen atmosphere (degassed by oxygen for three times) with a balloon filled. The reaction mixture was stirred at 100 o C for 48h. After cooling, saturated ammonium chloride solution (3 ml), and EtOAc (5 ml) were added to the reaction mixture. The organic phase was separated, and the aqueous phase was further extracted with EtOAc (3 x 3 ml). The combined organic fractions were dried over anhydrous Na2SO4, filtered through Celite, and concentrated. The residue was purified by silica gel chromatography using a mixture of hexanes and EtOAc to provide the desired carbazole 3h ( g, 65%) and 4h ( g, 33%). General Procedure for the Synthesis of Carbazoles (from 1h to 3h and 4h): To a solution of PdCl2(PPh3)2 (56.08 mg, mmol. 20 mol%), 4Å molecular sieve powder (187.5 mg,150 wt %), Cs2CO3 (260.6 mg, 0.8 mmol), along with 125 mg (0.4 mmol) substrate 1h in DMSO : toluene (1 ml: 1 ml) in a Schlenk Pressure Tube (10 ml) under a dry oxygen atmosphere (degassed by oxygen for three times) with a balloon filled. The reaction mixture was stirred at 100 o C for 48h. After cooling, saturated ammonium chloride solution (3 ml), and EtOAc (5 ml) were added to the reaction mixture. The organic phase was separated, and the aqueous phase was further extracted with EtOAc (3 x 3 ml). The combined organic fractions were dried over S-10

11 anhydrous Na2SO4, filtered through Celite, and concentrated. The residue was purified by silica gel chromatography using a mixture of hexanes and EtOAc to provide the desired carbazole 3h (54.5 mg, 51%) and 4h (16.0 mg, 24%). tert-butyl 9H-carbazole-9-carboxylate (3h): 1 H NMR (400 MHz, CDCl3): δ 8.31 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 7.6 Hz, 2H), 7.47 (t, J = 8.0 Hz, 2H), 7.36 (d, J = 7.6 Hz, 2H), 1.77 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 151.1, 138.5, 127.0, 125.7, 122.9, 119.5, 116.3, 83.9, H-carbazole (4h): 1 H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 7.6 Hz, 2H), 8.04 (s, 1H), (m, 4H), (m, 2H); 13 C NMR (101 MHz, CDCl3): δ 139.5, 125.8, 123.1, 120.3, 119.4, To a solution of benzoic acid or sodium benzoate (0.5 mmol), BocNH2, BocNHOH or BocNHOH (0.5 mmol), PdCl2(PPh3)2 ( g, mmol, 5 mol%), and Cs2CO3 ( g, 1 mmol) in toluene (3 ml) in a Schlenk Pressure Tube (10 ml) under a dry argon atmosphere. The reaction mixture was vigorously stirred at 85 o C for 3 h, unfortunately, no acetoxycarbamates decarboxylative product was observed. Characterization data Table 2, entry 1 2a White solid; mp: o C; g, 86% yield; 1 H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 7.8 Hz, 1H), (m, 2H), 6.98 (t, J = 7.2 Hz, 1H), 6.30 (brs, 1H), 2.25 (s, 3H), 1.54 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 153.0, 136.3, 130.2, 127.3, 126.7, 123.6, 120.9, 80.3, 28.3, S-11

12 (1) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, Table 2, entry 2 2b White solid; mp: o C; g, 45% yield; 1 H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.9 Hz, 2H), (m, 2H), (m, 1H), 6.60 (s, 1H), 1.53 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.8, 138.3, 128.9, 122.9, 118.5, 80.4, (1) Chankeshwara, S. V.; Chakraborti, A. K. Tetrahedron Lett. 2006, 47, (2) Chankeshwara, S. V.; Chakraborti, A. K. Org. Lett. 2006, 8, Table 2, entry 3 2c Colorless oil; g, 83% yield; 1 H NMR (400 MHz, CDCl3): δ (d, J = 5.6 Hz, 1H), 7.11 (s, 1H), (m, 2H), (m, 1H), 3.85 (s, 3H), 1.51 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.7, 147.4, 128.0, 122.2, 120.9, 117.9, 109.8, 80.1, 55.5, (1) Ma, F.; Xie, X.; Zhang, L.; Peng, Z.; Ding, L.; Fu, L.; Zhang, Z. J. Org. Chem. 2012, 77, Table 2, entry 4 2d White solid; mp: o C; g, 70% yield; 1 H NMR (400 MHz, CDCl3): δ 8.08 (t, J = 7.8 Hz, 1H), (m, 1H), (m, 1H), (m, 1H), 6.72 (s, 1H), 1.53 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.4, (d, J = Hz), (d, J = 10.0 Hz), (d, J = 3.7 Hz), (d, J = 7.5 Hz), 120.0, (d, J = 19.2 Hz), 80.9, S-12

13 (1) Jensen, T.; Pedersen, H.; Andersen, B. B.; Madsen, R.; Jørgensen M. Angew. Chem. Int. Ed., 2008, 47, Table 2, entry 5 2e Colorless oil; g, 91% yield; 1 H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.5 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.23 (t, J = 8.5 Hz, 1H), 7.00 (s, 1H) 6.94 (t, J = 8.0 Hz, 1H), 1.53 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.3, 135.2, 128.9, 127.6, 123.2, 121.8, 119.8, 81.0, (1) Yamaguchi, M.; Manabe, K. Org. Lett. 2014, (2) Boyer, J. H.; Fu, P. P. J. Org. Chem. 1972, 37, Table 2, entry 6 2f Yellow solid; mp: o C; g, 87% yield; 1 H NMR (400 MHz, CDCl3): δ 9.64 (s, 1H), 8.55 (dd, J = 8.6, 1.0 Hz, 1H), 8.17 (dd, J = 8.5, 1.5 Hz, 1H), (m, 1H), 7.07 (ddd, J = 8.4, 7.4, 1.2 Hz, 1H), 1.54 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.1, 135.9, 135.7, 125.8, 121.8, 120.6, 81.8, (1) Davis, M. C.; Groshens, T. J. Tetrahedron Lett. 2012, 53, Table 2, entry 7 2g oil; g, 83% yield; 1 H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.52 (t, J = 7.9 Hz, 1H), 7.13 (t, J = 7.7 Hz, 1H), 6.80 (s, 1H), 1.53 (s, 9H); 13 C NMR (101 MHz, CDCl3); δ 152.5, 136.2, 132.8, (q, J = 5.4 Hz), (q, J = Hz), 123.0, 122.3, (q, J = 29.7 Hz), 81.3, S-13

14 (1) Bellezza, F.; Cipiciani, A.; Ruzziconi, R.; Spizzichino, S. J. Fluorine Chem. 2008, 129, Table 2, entry 8 2h White solid; mp: o C; g, 90% yield; 1 H NMR (400 MHz, CDCl3): δ 8.13 (d, J = 8.5 Hz, 1H), 7.50 (t, J = 7.6 Hz, 2H), (m, 4H), 7.21 (d, J = 7.6 Hz, 1H), (m, 1H), 6.52 (s, 1H), 1.48 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.8, 138.3, 135.2, 131.3, 130.1, 129.2, 129.0, 128.3, 127.7, 123.0, 119.7, 80.4, (1) Tsang, W. C. P.; Munday, R. H.; Brasche, G.; Zheng, N.; Buchwald, S. L. J. Org. Chem. 2009, 74, Table 2, entry9 2i White solid; mp: o C; g, 88% yield; 1 H NMR (400 MHz, CDCl3): δ 7.52 (s, 1H), (m, 2H), (m, 1H), 6.63 (s, 1H), 1.51 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.5, 139.6, 134.7, 129.9, 123.0, 118.6, 116.5, 81.0, (1) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L. M. J. Org. Chem. 1999, 64, Table 2, entry10 2j White solid; mp: o C; g, 73% yield; 1 H NMR (400 MHz, CDCl3): δ 7.52 (d, J = 7.6 Hz, 1H), 7.08 (t, J = 8.0 Hz, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.25 (s, 1H), 2.29 (s, 3H), 2.15 (s, 3H), S-14

15 1.52 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 153.5, 137.1, 135.9, 127.6, 126.1, 125.8, 120.3, 80.2, 28.4, 20.7, (1) Chankeshwara, S. V.; Chakraborti, A. K. Org. Lett. 2006, 8, Table 2, entry 11 2k White solid; mp: o C; g, 61% yield; IR (film) 3205, 3128, 2975, 1724, 1353, 1156, 1012, 847, 520 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ 7.38 (s, 2H), 6.10 (s, 1H), 1.49 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.6, 137.0, 128.9, 127.9, 119.7, 80.8, Anal. Calcd for C11H12Cl3NO2: C, 44.55; H, 4.08; N, Found: C, 44.50; H, 4.04; N, GC-MS: Found: Table 2, entry 12 2l White solid; mp: o C; g, 75% yield; 1 H NMR (400 MHz, CDCl3): δ 7.24 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.2 Hz, 2H), 6.43 (br, 1H), 2.29 (s, 3H), 1.52 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.9, 135.7, 132.5, 129.4, 118.7, 80.3, 28.3, (1) Ma, F.; Xie, X.; Zhang, L.; Peng, Z.; Ding, L.; Fu, L.; Zhang, Z. J. Org. Chem. 2012, 77, Table 2, entry 13 2m White solid; mp: o C; g, 71% yield; 1 H NMR (400 MHz, CDCl3): δ (m, 2H), 6.83 (d, J = 8.8 Hz, 2H), 6.32 (br, 1H), 3.77 (s, 3H), 1.51 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 155.7, 153.2, 131.5, 120.6, 114.3, 80.2, 55.6, S-15

16 (1) Jensen, T.; Pedersen, H.; Bang-Andersen, B.; Madsen, R.; Jørgensen, M. Angew. Chem. Int. Ed. 2008, 47, Table 2, entry 14 2n White solid; mp: o C; g, 72% yield; 1 H NMR (400 MHz, CDCl3): δ 7.30 (d, J = 8.5 Hz, 2H), (m, 2H), 6.60 (s, 1H), 1.51 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.6, 137.0, 128.9, 127.9, 119.7, 80.8, (1) Roosen, P. C.; Kallepalli, V. A.; Chattopadhyay, B.; Singleton, D. A.; Maleczka, R. E., Jr.; Smith, M. R. J. Am. Chem. Soc. 2012, 134, Table 2, entry 15 2o White solid; mp: o C; g, 60% yield; 1 H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 9.2 Hz, 2H), 7.52 (d, J = 9.2 Hz, 2H), 8.88 (s, 1H), 1.54 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 151.8, 144.4, 142.6, 125.2, 117.4, 81.9, (1) Wang, J.; Liang, Y.-L.; Qu, J. Chem. Commun. 2009, Table 2, entry 16 2p White solid; mp: o C; g, 45% yield; 1 H NMR (400 MHz, CDCl3): δ (m, 4H), (m, 4H), 7.31 (t, J = 8.0 Hz, 1H), 6.51 (s, 1H) 1.54 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.7, 140.6, 137.6, 135.9, 128.7, 127.6, 126.9, 126.7, 118.8, 80.6, (1) Serpil, B.; Meike S.; Umut S.; Marcel M. Angew. Chem. Int. Ed. Engl. 2009, 48, S-16

17 Table 2, entry 17 2q White solid; mp: o C; g, 42% yield; 1 H NMR (400 MHz, CDCl3): δ 7.96 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 6.77 (br, 1H), 3.88 (s, 3H), 1.51 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 166.7, 152.1, 142.7, 130.8, 124.3, 117.3, 81.1, 51.8, (1) Ishii, H.; Minegishi, K.; Nagatsu, K.; Zhang, M.-R. Tetrahedron 2015, 71, Table 3, entry 1 2aa White solid; mp: o C; g, 75% yield; 1 H NMR (400 MHz, CDCl3): δ (m, 1H), (m, 1H), 7.63 (s, 1H), (m, 2H), (m, 1H), 6.66 (s, 1H), 2.57 (s, 3H), 1.47 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 153.7, 132.9, 131.2, 130.9, 128.8, 127.1, 126.3, 125.6, 124.8, 121.2, 119.3, 80.4, 28.3, (1) Augustine, J. K.; Bombrun, A.; Mandal, A. B.; Alagarsamy, P.; Atta, R. N.; Selvam, P. Synthesis 2011, 9, Table 3, entry 2 2ab White solid; mp: o C; g, 70% yield; IR (film) 3446, 2957, 1701, 1542, 1230, 1082, 750 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ (m, 1H), (m, 1H), 7.68 (s, 1H), (m, 2H), 7.31 (d, J = 7.6 Hz, 1H), 6.83 (s, 1H), 3.99 (d, J = 6.4 Hz, 2H), 2.67 (s, 3H), (m, 1H), 0.98 (d, J = 5.6 Hz,6H); 13 C NMR (101 MHz, CDCl3): δ 154.9, 133.0, 131.6, S-17

18 130.8, 126.4, 125.8, 125.7, 124.9, 121.3, 71.6, 28.0, 19.3, Anal. Calcd for C16H19NO2: C, 74.68; H, 7.44; N, Found: C, 74.66; H, 7.41; N, GC-MS: Found: Table 3, entry 3 2ac White solid; mp: o C; g, 67% yield; 1 H NMR (400 MHz, CDCl3): δ (m, 4H), (m, 1H), 6.59 (d, J = 7.2 Hz, 1H), 5.89 (d, J = 14.4 Hz, 1H), 1.47 (s, 9H); 13 C NMR (101 MHz, CDCl3): δ 152.7, 136.5, 128.5, 125.9, 125.1, 124.3, 109.6, 80.7, (1) Min, G. K.; Hernández, D.; Lindhardt, A. T.; Skrydstrup, T.; Organic Lett. 2010, 12, Table 3, entry 4 2ad Oil; g, 71% yield; IR (film) 3430, 2955, 1745, 1530, 1243, 1041, 751, 544 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ 8.16 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.26 (t, J = 8.0 Hz, 1H), 7.12 (s, 1H), 6.98 (t, J = 8.0 Hz, 1H), 3.97 (d, J = 6.8 Hz, 2H), (m, 1H), 0.97 (d, J = 6.4 Hz, 6H); 13 C NMR (125 MHz, CDCl3): δ 153.4, 134.9, 129.1, 127.9, 123.7, 122.1, 119.9, 71.7, 28.1, 19.1; Anal. Calcd for C11H14ClNO2: C, 58.03; H, 6.20; N, Found: C, 58.11; H, 6.05; N, GC-MS: Found: Table 3, entry 5 2ae S-18

19 White solid; mp: o C; g, 87% yield; 1 H NMR (400 MHz, CDCl3): δ 8.18 (d, J = 8.0 Hz, 1H), (m, 7H), 7.21 (s, 1H), 6.98 (t, J = 8.0 Hz, 1H), 5.18 (s, 2H); 13 C NMR (101 MHz, CDCl3): δ 152.9, 140.2, 135.7, 134.6, 129.0, 128.6, 128.4, 128.4, 127.7, 123.7, 119.8, (1) Cooley, J. H.; Jacobs, P. T. J. Org. Chem. 1975, 40, Table 3, entry 6 2af White solid; mp: o C; g, 63% yield; 1 H NMR (400 MHz, CDCl3): δ 7.76 (s, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.04 (t, J = 7.6 Hz, 1H), 6.42 (s, 1H), 3.78 (s, 3H), 2.25 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 154.4, 135.8, 130.4, 128.0, 126.8, 124.2, 121.3, 52.4, (1) Crane, Z. D.; Nichols, P. J.; Sammakia, T.; Stengel, P. J. J. Org. Chem. 2011, 76, Table 3, entry 7 2ag White solid; mp: o C; g, 58% yield; 1 H NMR (400 MHz, CDCl3): δ 7.81 (d, J = 6.8 Hz, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 6.34 (s, 1H), 5.03 (sept, J = 6.4 Hz, 1H), 2.26 (s, 3H), 1.31 (d, J = 6.4 Hz, 6H); 13 C NMR (101 MHz, CDCl3): δ 153.5, 136.1, 130.3, 127.3, 126.8, 123.8, 120.9, 68.7, 22.1, (1) Ghosh, R.; Nethaji, M.; Samuelson, A. G. J. Organomet. Chem.2005, Table 3, entry 8. 2ah Oil; g, 60% yield; 1 H NMR (400 MHz, CDCl3): δ 7.78 (s, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 7.2 Hz, 1H), 7.03 (t, J = 7.2 Hz, 1H), 6.39 (s, 1H), 3.96 (d, J = 6.8 Hz, 2H), 2.26 (s, S-19

20 3H), 1.99 (sept, J = 6.4 Hz, 1H), 0.97 (d, J = 6.8 Hz, 6H); 13 C NMR (101 MHz, CDCl3): δ 154.1, 135.9, 130.4, 126.9, 124.1, 121.2, 71.5, 28.0, 19.1, (1) Yang, H.; Huang, D.; Wang, K.-H.; Xu, C.; Niu, T.; Hu, Y. Tetrahedron 2013, 69, Table 3, entry 9 2ai White solid; mp: o C; g, 72% yield; 1 H NMR (400 MHz, CDCl3): δ 7.79 (s, 1H), (m, 5H), 7.18 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 7.01 (t, J = 7.2 Hz, 1H), 6.49 (s, 1H), 5.19 (s, 2H) 2.20 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 153.6, 136.1, 135.7, 130.3, 128.5, 128.3, 128.2, 127.6, 126.8, 124.2, 121.1, 67.0, (1) Wipf, P.; Maciejewski, J. P. Org. Lett. 2008, 10, Table 3, entry 10 2aj Oil; g, 70% yield; 1 H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 6.0 Hz, 1H), 7.23 (s, 1H), (m, 2H), (m, 1H), 4.23 (q, J = 6.8 Hz, 2H), 3.85 (s, 3H), 1.32 (t, J = 7.2 Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ 153.6, 147.6, 127.8, 122.6, 121.1, 118.2, 109.9, 61.1, 55.6, (1) Lu, Y.; Taylor, R. T. Tetrahedron Let. 2003, 44, Table 3, entry 11 2ak S-20

21 Oil; g, 75% yield; IR (film) 3437, 2958, 1701, 1603, 1233, 1056, 756, 567 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 4.4 Hz, 1H), 7.22 (s, 1H), (m, 2H), (m, 1H), 4.18 (t, J = 6.8 Hz, 2H), 3.86 (s, 3H), (m, 2H), (m, 2H), 0.96 (t, J = 7.2 Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ 153.7, 147.6, 127.8, 122.6, 121.1, 118.1, 109.9, 65.0, 55.6, 31.0, 19.1, 13.8; Anal. Calcd for C12H17NO3: C, 64.55; H, 7.67; N, Found: C, 64.57; H, 7.63; N, GC-MS: Found: Table 3, entry 12 2af Oil; g, 70% yield; IR (film) 3428, 2958, 1739, 1530, 1221, 1054, 741, 576 cm -1 ; 1 H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 4.8 Hz, 1H), 7.23 (s, 1H), (m, 2H), (m, 1H),4.17 (t, J = 6.8 Hz, 2H), 3.85 (s, 3H), (m, 2H), (m, 4H), 0.93 (t, J = 6.4 Hz, 3H); 13 C NMR (101 MHz, CDCl3): δ 153.7, 147.6, 127.8, 122.6, 121.1, 118.1, 109.9, 65.3, 55.6, 28.7, 28.0, 22.4, 13.9; Anal. Calcd for C13H19NO3: C, 65.80; H, 8.07; N, Found: C, 65.82; H, 8.05; N, GC-MS: Found: S-21

22 S-22

23 S-23

24 S-24

25 S-25

26 S-26

27 S-27

28 9 S-28

29 S-29

30 S-30

31 S-31

32 S-32

33 S-33

34 S-34

35 S-35

36 S-36

37 S-37

38 S-38

39 S-39

40 S-40

41 S-41

42 S-42

43 S-43

44 S-44

45 S-45

46 S-46

47 S-47

48 S-48

49 S-49

50 S-50

51 S-51

52 S-52

53 S-53

54 S-54

55 S-55

56 S-56

57 S-57

58 S-58

59 S-59

60 S-60

61 S-61

62 S-62

63 S-63

64 C S-64

65 S-65

66 S-66

67 S-67

68 S-68

69 S-69

70 S-70

71 S-71

72 S-72

73 S-73

74 S-74

75 S-75

76 S-76

77 S-77

78 S-78

79 S-79

80 S-80

81 S-81

82 S-82

83 S-83