Brønsted Acid-Catalyzed Hydroarylation of Activated. Olefins

Transcript

1 Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 204 Brønsted Acid-Catalyzed Hydroarylation of Activated Olefins Ivana Fleischer* and Jola Pospech Supporting Information. Analytical Methods Materials and Methods Experimental Procedures and Analytical Data Additional Tables General Procedure for the Synthesis of Substrates Characterization of the Substrates General Procedure for the Hydroarylation Characterization of the Hydroarylation Products...22

2 . Analytical Methods NMR spectra were recorded on Bruker Avance 300 (300 MHz) and Bruker Avance 400 (400 MHz) NMR spectrometers. Chemical shifts (ppm) are given relative to solvent: references for CDCl 3 were 7.26 ppm ( H-NMR) and 77.6 ppm ( 3 C-NMR) and for CD 2 Cl ppm ( H-NMR) and 54.0 ppm ( 3 C-NMR). 3 C-NMR spectra were acquired on a broad band decoupled mode. Multiplets were assigned as s (singlet), d (doublet), t (triplet), dd (doublet of doublet), m (multiplet) and br. s (broad singlet). All measurements were carried out at room temperature unless otherwise stated. Electron impact (EI) mass spectra were recorded on AMD 402 mass spectrometer (70 ev). High resolution mass spectra (HRMS) were recorded on Agilent 620 Time-of-Flight LC/MS (Agilent) with electrospray ionization (ESI). The data are given as mass units per charge (m/z) and intensities of signals are given in brackets. For GC analyses, HP 6890 chromatograph with a 30 m HP5 column was used. The enantiomeric excess was determined by HPLC (HP 00 equipped with diode array detector) using Whelk-O (S,S) column. 2. Materials and Methods All commercial reagents were purchased from Acros Organics, Alfa Aesar, Aldrich or Strem. Dry solvents were prepared according to standard procedures. Air- and moisture-sensitive syntheses were performed under argon atmosphere in heating gun vacuum dried glassware. Catalytic reactions were performed in screw cup equipped glass pressure tubes. 2

3 3. Experimental Procedures and Analytical Data 3.. Additional Tables Table SI. Optimization: solvents at 60 C with A4. a + N H A4 (5 mol%) solvent 60 C, 6 h a 2a 3aa Entry a Solvent Conv. a (%) b Yield 3aa (%) b DCM Me MeCN Toluene THF 6 H 2 O DMF DMSO DCE c H 2 O c DCM d DCM DCM e H 2 O (55) f 5 e DCM (88) f a Reaction conditions: a (60. mg, mmol), 2a (64.4 mg, mmol), A4 (6.2 mg, 25 µmol) in DCM ( ml), 60 C, 6 h. b Determined by GC with isooctane as internal standard. c 20 h. d 0.5 ml solvent. e 80 C. f Isolated yields are given in brackets. 3

4 Table SI2. Chiral acids. a + N H acid (0 mol%) DCM 60 C, 20 h a 2a 3aa Acids: R O O R O P A7 R = 3,5-(CF 3 ) 2 C 6 H 3 A8 R = SiPh 3 ent-a9 R = 9-phenantrenyl Ph O O A0 R = 2,4,6- i P Pr 3 C 6 H 2 Ph O A Entry Acid Yield 3aa (%) b e.r. 3aa (R/S) c A :52 2 A :53 3 A :43 4 A :52 5 A 74 50:50 6 d A9 6 56:44 a Reaction conditions: a (30.0 mg, mmol), 2a (32.2 mg, mmol), acid (25 µmol) in DCM ( ml), 60 C, 20 h (with a, 2a stock solution). b Isolated yield. c Determined by HPLC on a chiral stationary phase. d Performed with 25 µmol a at C, 87 h. 4

5 3.2. General Procedure for the Synthesis of Substrates 2 Alkyltriphenylphosphonium bromide (2.46 g, 6.90 mmol) was added to a 250 ml 3-necked flask under argon and suspended in THF (0 ml). A solution of potassium tert-butoxide (784 mg, 6.99 mmol) in THF (5 ml) was added and the reaction mixture was stirred at ambient temperature for 4 h. The resulting orange solution was cooled down to -78 C and a THF solution (2 ml) of the aldehyde (3.00 mmol) was added drop wise. The reaction mixture was allowed to warm to ambient temperature overnight. A saturated solution of 4 Cl (5 ml) was added, the mixture was diluted with Et 2 O (0 ml), washed with water (2 0 ml) and brine (0 ml). The organic layer was dried over Na 2 SO 4 and concentrated in vacuo. The crude product was purified by column chromatography. 5

6 3.3. Characterization of the Substrates 2-Vinylphenol (a) According to the general procedure, a was prepared from methyltriphenylphosphonium bromide (3.5 g, 37.7 mmol), potassium tert-butoxide (4.29 g, 38.2 mmol) and salicyl aldehyde (2.00 g, 6.4 mmol). The crude thick yellow oil was purified by column chromatography (silica, Et 2 O/pentane 0:90-20:80) to yield the product as a pale yellow oil, which solidified upon standing below room temperature (.85 g, 89%, 95% purity). The analytical data were in accordance with the literature. 3 C 8 H 8 O (20.5 g/mol) R f = 0.28 (silica, EA/heptane :5). M.p.: ambient temperature H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.40 (dd, 3 J HH = 7.7 Hz, 4 J HH =.7 Hz, H, 3-H), 7.5 (ddd, 3 J HH = 8.0, 7.4 Hz, 4 J HH =.7 Hz, H, 5-H), (m, 2H, 4-H, CH=CH 2 ), 6.80 (dd, 3 J HH = 8.0 Hz, 4 J HH =.2 Hz, H, 6-H), 5.76 (dd, 3 J HH = 7.7 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 5.37 (dd, 3 J HH =.2 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 5.2 (br. s, H, ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 52.9 (C-), 3.6 (CH=CH 2 ), 29.0 (C-3), 27.5 (C-5), 24.9 (C-2), 2. (C-4), 6.03 (C-6), 5.98 (CH=CH 2 ). GC MS (EI) m/z (%): 20 (64, M + ), 9 (00, C 7 H 7+ ), 77 (4, C 6 H 5+ ), 65 (4, C 5 H 5+ ), 5 (8, C 4 H 3+ ), 39 (, C 3 H 3+ ). GC (HP5 30 m, 35 C/0 min/0 C/min/285 C/5 min, DCM): t R = 20.3 min. 6

7 a a 7

8 4-Vinylphenol (b) HO 4-Vinylphenyl acetate (500 mg, 3.08 mmol) was dissolved in THF (5 ml) and treated with an aqueous sodium hydroxide solution (5 m, 3 ml, 5 mmol). The reaction mixture was stirred at ambient temperature and monitored by TLC. After 30 minutes, the mixture was neutralized by M HCl and extracted with DCM (3 0 ml). The organic phase was separated using Whatmann phase separator and concentrated in vacuo to desired concentration (for standard conditions 0.5 M) and directly used in the next step. C 8 H 8 O (20.5 g/mol) R f = 0.20 (silica, EA/heptane :4). 6-Vinylnaphthalen-2-ol (d) HO According to the general procedure, d was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and 6-hydroxy-2- naphthaldehyde (56 mg, 3.00 mml). The crude thick yellow oil was purified by column chromatography (silica, Et 2 O/pentane 0:90) to yield the product as a colorless solid (382 mg, 75%). C 2 H 0 O 2 (70.2 g/mol) R f = 0.26 (silica, EA/heptane :4). H NMR (300 MHz, CD 3 CN) δ/ppm: (m, 4H, ArH), 7.25 (s, H, ), (m, 2H, ArH), 6.86 (dd, 3 J HH = 7.6 and 0.9 Hz, H, CH=CH 2 ), 5.84 (dd, 3 J HH = 7.6 Hz, 2 J HH =.0 Hz, H, CH=CH A H B ), 5.26 (dd, 3 J HH = 0.9 Hz, 2 J HH =.0 Hz, H, CH=CH A H B ). 3 C NMR (75 MHz, CD 3 CN) δ/ppm: 56.0 (C-2), 37.9 (CH=CH 2 ), 35.6 (ArC), 33.5 (ArC), 30.7 (ArH), 29.4 (ArC), 27.5 (ArH), 27. (ArH), 24.5 (ArH), 9.4 (ArH), 3.6 (CH=CH 2 ), 0.0 (ArH). MS (EI) m/z (%): 70 (00, M + ), 53 (6, [M-] + ), 4 (25, [M-CHO] + ), 5 (5, C 9 H 7+ ), 84 (7), 72 (5), 63 (3). HRMS (EI) m/z (%): calculated for C 2 H 0 O 2 [M] ; found IR (ATR) ν /cm - : 3256m (), 3087w, 3000w, 86w, 628m, 576m, 50m, 480m, 353m, 270m, 226m, 60m, 992m, 907m, 902m, 892s (Ar), 868s (Ar), 809s (Ar), 624m. 8

9 HO d HO d 9

10 2-(Prop-2-en-2-yl)phenol (h) According to the general procedure, h was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and 2- hydroxyacetophenone (408 mg, 3.00 mmol). The crude product was purified by column chromatography (silica, Et 2 O/pentane 5:95) to yield the product as a pale yellow oil (20 mg, 83%, 90% purity). The analytical data were in accordance with the literature. 2 C 9 H 0 O (34.8 g/mol) R f = 0.35 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: (m, 2H, PhH), (m, 2H, PhH), 5.72 (s, H, ), (m, H, C=CH A H B ), (m, H, C=CH A H B ), 2.3 (s, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 52.0 (C-), 42.2 (C=CH 2 ), 29.0 (C-2), 28.7 (ArH), 27.9 (ArH), 20.3 (ArH), 5.9 (C-6), 5.7 (C=CH 2 ), 24.4 (CH 3 ). GC MS (EI) m/z (%): 34 (85, M + ), 9 (46, [M-CH 3 ] + ), 5 (6), 05 (7), 9 (00, C 7 H 7+ ), 77 (7, C 6 H 5+ ), 65 (4, C 5 H 5+ ), 5 (2, C 4 H 3+ ), 39 (4, C 3 H 3+ ). 0

11 h h

12 2-(Buta-,3-dien--yl)phenol (i) 4 n-butyllithium (3.7 ml of.6 M solution in hexanes, 5.9 mmol) was added to a solution of allyltriphenylphosphonium bromide (2.33 g, 6.09 mmol) in THF (0 ml) at -8 C. The mixture was stirred for 30 minutes at -8 C, then a THF (5 ml) solution of salicyladehyde (369 mg, 3.02 mmol) was added dropwise. The reaction mixture was stirred at -8 C for an additional hour and was let to warm to ambient temperature overnight. A saturated solution of 4 Cl (5 ml) was added, the mixture was diluted with Et 2 O (0 ml), washed with water (2 0 ml) and brine (0 ml). The organic layer was dried over Na 2 SO 4 and concentrated in vacuo. The crude orange product was purified by column chromatography (silica, Et 2 O/pentane 3:97-5:85) to yield i as a yellow oil, which solidified upon standing (308 mg, 70%). The analytical data were in accordance with the literature. 4 C 0 H 0 O (46.9 g/mol) R f = 0.24 (silica, EA/heptane :4). M.p.: ambient temperature H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.43 (dd, 3 J HH = 7.7 Hz, 4 J HH =.7 Hz, H, 3-H), 7.2 (ddd, 3 J HH = 8. and 7.4 Hz, 4 J HH =.7 Hz, H, 5-H), 6.92 (ddd, 3 J HH = 7.4 and 7.4 Hz, 4 J HH =.2 Hz, H, 4-H), (m, 3H, 6-H, -H, 2 -H), (m, H, 3 -H), 5.34 (dd, 3 J HH = 6.9 Hz, 2 J HH =.7 Hz, H, CH=CH A H B ), 5.9 (dd, 3 J HH = 0.0 Hz, 2 J HH =.7 Hz, H, CH=CH A H B ), 5.00 (br. s, H, ). 3 C NMR (75 MHz, CD 3 CN) δ/ppm: 52.9 (C-), 37.6 (CH=CH 2 ), 3. (CH), 28.7 (CH), 27.2 (CH), 27. (CH), 24.4 (CH), 2. (CH), 7.62 (CH=CH 2 ), 5.9 (CH). MS (EI) m/z (%): 46 (75, M + ), 45 (00, [M-H] + ), 3 (82, [M-CH 3 ] + ), 27 (38, [M-H 3 O] + ), 7 (22, [M-CHO] + ), 9 (7, C 7 H 7+ ), 77 (9, C 6 H 5+ ), 5 (5, C 4 H 3+ ), 39 (5, C 3 H 3+ ). HRMS (EI) m/z (%): calculated for C 0 H 0 O [M] ; found IR (ATR) ν /cm - : 3386m (), 3037w, 294w, 595m, 484m, 453s, 328m, 299m, 228s, 74m, 089m, 004m, 97m, 899m, 853w, 748s (Ar). 2

13 i i 3

14 4-tert-Butyl-2-vinylphenol (k) According to the general procedure, k was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and 2-hydroxy-5- tert-butylbenzaldehyde (56 mg, 2.90 mmol). The crude thick yellow oil was purified by column chromatography (silica, Et 2 O/pentane 0:90) to yield the product as a pale yellow oil (450 mg, 88%). C 2 H 6 O (76.25 g/mol) R f = 0.35 (silica, EA/heptane :4). H NMR (400 MHz, CDCl 3 ) δ/ppm: 7.40 (d, 4 J HH = 2.5 Hz, H, 3-H), 7.9 (dd, 3 J HH = 8.4 Hz, 4 J HH = 2.5 Hz, H, 5-H), 6.95 (dd, 3 J HH = 7.8 and.2 Hz, H, CH=CH 2 ), 6.75 (d, 3 J HH = 8.4 Hz, H, 6-H), 5.76 (dd, 3 J HH = 7.8 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 5.37 (dd, 3 J HH =.2 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 4.98 (s, H, ),.32 (s, 9H, C(CH 3 ) 3 ). 3 C NMR (0 MHz, CDCl 3 ) δ/ppm: 50.7 (C-), 43.7 (C-4), 32.3 (CH=CH 2 ), 26. (ArH), 24.3 (ArH), 24. (C-2), 5.7 (CH=CH 2 ), 5.6 (C-6), 34.2 (C(CH 3 ) 3 ), 3.6 (C(CH 3 ) 3 ). GC MS (EI) m/z (%): 76 (23, M + ), 6 (00, [M-CH 3 ] + ), 33 (6, [M-CO-CH 3 ] + ), 9 (79, C 7 H 7+ ), 77 (26, C 6 H 5+ ), 63 (0), 5 (7, C 4 H 3+ ), 39 (0, C 3 H 3+ ). HRMS (EI) m/z (%): calculated for C 2 H 6 O [M] ; found IR (ATR) ν /cm - : 3406m (), 2960s (CH 3 ), 2903m, 2868m, 626m, 607w, 496s, 48m, 363m, 268s, 234m, 79m, 24m, 090m, 994m, 905m, 87s (Ar), 679m. 4

15 k k 5

16 4-Methyl-2-vinylphenol (l) According to the general procedure W2, l was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and 2- hydroxy-5-methylbenzaldehyde (408 mg, 3.00 mmol). The crude thick yellow oil was purified by column chromatography (silica, Et 2 O/pentane 20:80) to yield the product as a pale yellow oil (374 mg, 9%, 98% purity). C 9 H 0 O (34.8 g/mol) R f = 0.26 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.2 (d, 4 J HH = 2.2 Hz, H, 3-H), (m, 2H, 5-H, CH=CH 2 ), 6.70 (d, 3 J HH = 8. Hz, H, 6-H), 5.75 (dd, 3 J HH = 7.7 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 5.35 (dd, 3 J HH =.2 Hz, 2 J HH =.4 Hz, H, CH=CH A H B ), 5.02 (br. s, H, ), 2.30 (s, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 50.7 (C-), 3.7 (CH=CH 2 ), 30.2 (C-4), 29.6 (C-5), 27.8 (C-3), 24.6 (C-2), 5.9 (C-6), 5.6 (CH=CH 2 ), 20.6 (CH 3 ). GC MS (EI) m/z (%): 34 (00, M + ), 9 (2, [M-CH 3 ] + ), 05 (3, [M-CHO] + ), 9 (79, C 7 H 7+ ), 77 (26, C 6 H 5+ ), 63 (0), 5 (7, C 4 H 3+ ), 39 (0, C 3 H 3+ ). HRMS (EI) m/z (%): calculated for C 9 H 0 O [M] ; found IR (ATR) ν /cm - : 3393m (), 3020w, 292w, 624m, 495s, 47m, 34m, 253s, 204s, 0m, 994m, 908m, 807s (Ar), 780m. 6

17 l l 7

18 Methyl 4-hydroxy-3-vinylbenzoate (m) COOMe According to the general procedure, m was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and methyl 3- formyl-4-hydroxybenzoate (540 mg, 3.00 mmol). The crude product was purified by column chromatography (silica, Et 2 O/pentane 20:80) to yield the product as a colorless solid (48 mg, 74%). C 0 H 0 O 3 (78.8 g/mol) R f = 0.46 (silica, EA/heptane :). H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.2 (d, 4 J HH = 2. Hz, H, 2-H), 7.83 (dd, 3 J HH = 8.5 Hz, 4 J HH = 2. Hz, H, 6-H), 6.96 (dd, 3 J HH = 7.7 and.2 Hz, H, CH=CH 2 ), 6.88 (d, 3 J HH = 8.5 Hz, H, 5-H), 6.80 (br s, H, ), 5.82 (dd, 3 J HH = 7.7 Hz, 2 J HH =.2 Hz, H, CH=CH A H B ), 5.39 (dd, 3 J HH =. Hz, 2 J HH =.2 Hz, H, CH=CH A H B ), 3.92 (s, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 67.8 (COOCH 3 ), 57.7 (C-4), 30.7 (CH), 29.4 (CH), 25. (C quart ), 22.3 (C quart ), 6.7 (CH=CH 2 ), 5.9 (C-5), 52.3 (CH 3 ). GC MS (EI) m/z (%): 78 (4, M + ), 47 (00, [M-OCH 3 ] + ), 9 (5, [M-COOCH 3 ] + ), 9 (2, C 7 H 7+ ), 65 (2), 5 (5, C 4 H 3+ ), 39 (4, C 3 H 3+ ). HRMS (EI) m/z (%): calculated for C 0 H 0 O 3 [M] ; found IR (ATR) ν /cm - : 336m (), 2956w, 888w, 807w, 678s, 60s, 505m, 430m, 358m, 263s, 223s, 33s, 093m, 004m, 979m, 898s, 832m, 753s (Ar), 635s. 8

19 COOMe m COOMe m 9

20 4-Nitro-2-vinylphenol (n) NO 2 According to the general procedure, n was prepared from methyltriphenylphosphonium bromide (2.46 g, 6.90 mmol), potassium tert-butoxide (784 mg, 6.99 mmol) and 5-nitro-2- hydroxybenzaldehyde (50 mg, 3.00 mmol). The crude product was purified by column chromatography (silica, Et 2 O/pentane 20:80) to yield the product as a yellow solid (367 mg, 74%). The analytical data were in accordance with the literature. 5 C 8 H 7 NO 3 (65.5 g/mol) R f = 0.46 (silica, EA/heptane :). H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.3 (d, 4 J HH = 2.7 Hz, H, 3-H), 8.06 (dd, 3 J HH = 8.9 Hz, 4 J HH = 2.7 Hz, H, 5-H), (m, 2H, 6-H, CH=CH 2 ), 6.09 (s, H, ), 5.88 (dd, 3 J HH = 7.7 Hz, 2 J HH = 0.9 Hz, H, CH=CH A H B ), 5.53 (dd, 3 J HH =.2 Hz, 2 J HH = 0.9 Hz, H, CH=CH A H B ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 58.7 (C-), 4.7 (C-4), 29.7 (CH=CH 2 ), 25.8 (C-2), 24.8 (ArH), 23.4 (ArH), 8.6 (CH=CH 2 ), 6.2 (C-6). GC MS (EI) m/z (%): 65 (00, M + ), 35 (37, [M-CH 2 O] + ), 07 (4), 9 (54, C 7 H 7+ ), 77 (23, C 6 H 5+ ), 65 (49), 5 (6, C 4 H 3+ ), 39 (8, C 3 H 3+ ). 20

21 NO n 2 NO n 2 2

22 3.4. General Procedure for the Hydroarylation The alkene (500 µmol), nucleophilic aromatic compound (550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol) were placed in a pressure tube under air and dissolved in DCM ( ml). The pressure tube was sealed and heated to 80 C for 6 h. After cooling down, the crude reaction mixture was adsorbed on silica gel and purified by column chromatography. 22

23 3.5. Characterization of the Hydroarylation Products 2-(-(H-Indol-3-yl)ethyl)phenol (3aa) 6 5 3' 2 4' 3 5' 4 2' ' 9' 8' 6' 7' The compound 3aa was prepared according to the general procedure for hydroarylation from 2-vinylphenol (60. mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 85:5) and obtained as yellow solid (05 mg, 88%). Crystals for X-ray analysis were obtained from heptane/ethanol. The analytical data were in accordance with the literature. 3 C 6 H 5 NO ( g/mol) R f = 0.6 (silica, EA/heptane :5). M.p.: C H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.98 (br. S, H, ), 7.4 (dd, 3 J HH = 8.0 Hz, 4 J HH = 0.8 Hz, H, 5 -H), 7.34 (ddd, 3 J HH = 8. Hz, 4 J HH = 0.9 Hz, 5 J HH = 0.8 Hz, H, 8 -H), 7.33 (dd, 3 J HH = 7.6 Hz, 4 J HH =.6 Hz, H, 3-H), 7.2 (ddd, 3 J HH = 8. and 6.0 Hz, 4 J HH = 0.8 Hz, H, 7 -H), 7.6 (ddd, 3 J HH = 7.8 and 7.8 Hz, 4 J HH =.6 Hz, H, 5-H), 7.05 (ddd, 3 J HH = 8.0 and 6.0 Hz, 4 J HH = 0.9 Hz, H, 6 -H), 7.03 (s, H, 2 -H), 6.96 (ddd, 3 J HH = 7.8 and 7.6 Hz, 4 J HH =.2 Hz, H, 4-H), 6.80 (dd, 3 J HH = 7.8 Hz, 4 J HH =.2 Hz, H, 6-H), 5.24 (br. S, H, ), 4.56 (q, 3 J HH = 7. Hz, H, CHCH 3 ),.76 (d, 3 J HH = 7. Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 54. (C-), 37.0 (C-9 ), 3.6 (C-2), 28.5 (C-3), 27.7 (C-5), 26.7 (C-4 ), 22.6 (C-7 ), 2.4 (C-2 ), 2.0 (C-4), 9.8 (C-5 ), 9.7 (C-6 ), 9.5 (C-3 ), 6.4 (C-6),.4 (C-8 ), 32.3 (CHCH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 237 (65, M + ), 222 (00, [M-CH 3 ] + ), 204 (7), 94 (5), 65 (9), 44 (7, [M-C 6 H 5 O] + ), 7 (97, C 8 H 7 N + ), 9 (3, C 7 H 7+ ), 77 (6, C 6 H 5+ ), 63 (5), 5 (3), 39 (3). GC (HP5 30 m, 35 C/0 min/0 C/min/285 C/5 min, DCM): t R = 32.3 min. HPLC: Whelk-O (S,S), heptane/ethanol 98:2,.0 ml/min, t R = 30.6 min (R), 32.8 min (S). 23

24 f (ppm) f (ppm) 3aa 3aa

25 HPLC trace of the enantiomerically enriched product (e.r. 57:43 R/S) 25

26 4-(-(H-Indol-3-yl)ethyl)phenol (3ba) HO 2 3 3' 4 4' 5' 2' ' 9' 8' 6' 7' The compound 3ba was prepared according to the general procedure for hydroarylation from 4-vinylphenol (60. mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0-80:20) and obtained as yellow solid (8 mg, 68%). The analytical data were in accordance with the literature. 3 C 6 H 5 NO ( g/mol) R f = 0.09 (silica, EA/heptane :4). M.p.: C H NMR (300 MHz, CD 3 CN) δ/ppm: 9.04 (br. S, H, ), 7.36 (d, 3 J HH = 8. Hz, H, 5 -H), 7.29 (d, 3 J HH = 8. Hz, H, 8 -H), (m, 4H, ArH), (m, H, ArH), (m, 3H,, 2-H), 4.28 (q, 3 J HH = 7.2 Hz, H, CHCH 3 ),.62 (d, 3 J HH = 7.2 Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CD 3 CN) δ/ppm: 55.8 (C-), 39.8 (C quart ), 37.8 (C quart ), 29.2 (C-3), 27.8 (C-4 ), 22.4 (ArH), 22.3 (ArH), 2.9 (C-3 ), 20.2 (ArH), 9.5 (ArH), 5.9 (C-2), 2.2 (C-8 ), 36.9 (CHCH 3 ), 22.9 (CH 3 ). GC MS (EI) m/z (%): 237 (3, M + ), 222 (00, [M-CH 3 ] + ), 204 (4), 92 (6), 65 (7), 44 (4, [M-C 6 H 5 O] + ), 7 (5), 77 (3, C 6 H 5+ ), 63 (2), 5 (2), 39 (2). HRMS (EI) m/z (%): calculated for C 6 H 4 NO [M-H] ; found IR (ATR) ν /cm - : 3423m (), 3050w, 2963w, 2854w, 63w, 50m, 455m, 40m, 33m, 256m, 83m, 68m, 09m, 009m, 96w, 825s, 744s, 608m. 26

27 f (ppm) f (ppm) 3ba HO 3ba HO

28 6-(-(H-Indol-3-yl)ethyl)naphthalen-2-ol (3da): 3 HO ' 6 3' ' 7 4' 5' 9' 8' 6' 7' The compound 3da was prepared according to the general procedure for hydroarylation from 6-vinylnapthtalen-2-ol (85. mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 95:5-80:20) and obtained as purple oil (63 mg, 43%). C 20 H 7 NO ( g/mol) R f = 0.08 (silica, EA/heptane :4). H NMR (400 MHz, CD 3 CN) δ/ppm: 9. (br. S, H, ), 7.69 (d, 4 J HH =.2 Hz, H, 5-H), 7.66 (d, 3 J HH = 8.7 Hz, H, 4-H), 7.57 (d, 4 J HH = 8.5 Hz, H, 8-H), 7.37 (ddd, 3 J HH = 8.2 Hz, 4 J HH = 0.9 Hz, 5 J HH = 0.8 Hz, H, 8 -H), 7.32 (dd, 3 J HH = 8.6 Hz, 4 J HH = 2.2 Hz, H, 7-H), 7.29 (ddd, 3 J HH = 8.0 Hz, 4 J HH =.9 Hz, 5 J HH = 0.8 Hz, H, 5 -H), 7.20 (dd, 3 J HH = 2.5 Hz, 5 J HH =.0 Hz, H, 2 -H), 7.3 (br. s, H, ), 7.0 (d, 4 J HH = 2.2 Hz, H, -H), (m, 2H, 3-H, 7 -H), 6.87 (ddd, 3 J HH = 8.0 and 7.0 Hz, 4 J HH = 0.9 Hz, H, 6 -H), 4.46 (q, 3 J HH = 7.2 Hz, H, CHCH 3 ),.72 (d, 3 J HH = 7. Hz, 3H, CHCH 3 ). 3 C NMR (0 MHz, CD 3 CN) δ/ppm: 55.3 (C-2), 43.2 (C-6), 37.8 (C-9 ), 34.4 (C-9), 30. (C-4), 29.5 (C-0), (C-4 ), (C-7), 27. (C-8), 25.9 (C-5), 22.5 (C-2 ), 22.4 (C-7 ), 2.4 (C-3 ), 20. (C-5 ), 9.5 (C-6 ), 9.0 (C-3), 2.2 (C-8 ), 09.7 (C-), 37.6 (CHCH 3 ), 22.6 (CH 3 ). GC MS (EI) m/z (%): 287 (35, M + ), 272 (00, [M-CH 3 ] + ), 242 (6), 25 (3), 44 (5, C 0 H 0 N + ), 36 (5), 5 (6, C 9 H 7+ ). HRMS (EI) m/z (%): calculated for C20H 7 NO [M] ; found

29 f (ppm) f (ppm) HO 3da HO 3da

30 4-(-(H-indol-3-yl)ethyl)aniline (3ea) H 2 N The compound 3ea was prepared according to the general procedure for hydroarylation from 4-vinylaniline (62.0 mg, 520 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0-80:20) and obtained as pale yellow solid (79 mg, 64%). C 6 H 5 N 2 ( g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.92 (s, H, ), 7.43 (dd, J = 8.0,.0 Hz, H, ArH), 7.32 (dt, J = 8.2,.0 Hz, H, ArH), (m, 4H), 6.96 (dd, J = 2.3,. Hz, H), (m, 2H), 4.3 (q, J = 7. Hz, H, CH), 3.46 (s, 2H, 2 ),.70 (d, J = 7.4 Hz, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 44.2 (C q ), 37.3 (C q ), 36.7 (C q ), 28.3 (CH), 27.0 (C q ), 22. (C q ), 2.9 (CH), 2. (CH), 9.9 (CH), 9.2 (CH), 5.4 (CH),. (CH), 36.2 (CH), 22.7 (CH 3 ). GC MS (EI) m/z (%): 236 (29, M + ), 22 (00), 204 (7), 92 (3), 65 (3), 0 (8). HRMS (EI) m/z (%): calculated for C 6 H 6 N [M+H] ; found IR (ATR) ν /cm - : 343m (), 3324 (w), 380 (bw), 2969 (w), 65 (w), 50 (m), 337 (m), 224 (m), 08 (w), 82 (s), 742 (s), 543 (s). 30

31 H 2 N 3ea f (ppm) H 2 N 3ea f (ppm)

32 2-(2-(H-indol-3-yl)propan-2-yl)phenol (3ha) 6 5 3' 2 4' 3 5' 4 2' ' 9' 8' 6' 7' The compound 3ha was prepared according to the general procedure for hydroarylation from 2-(prop-2-en-2-yl)phenol (76.8 mg, 544 µmol, 95% purity), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol) at 80 C. The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0) and obtained as a pale purple foamy solid (33 mg, 97%). C 7 H 7 NO (25.33 g/mol) M.p.: 8-9 C R f = 0.30 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.4 (br. S, H, ), 7.6 (dd, 3 J HH = 7.8 Hz, 4 J HH =.7 Hz, H, 5 -H), 7.35 (dd, 3 J HH = 8.3 Hz, 4 J HH =.0 Hz, H, 8 -H), 7.27 (s, H, 2 -H), (m, 2H, ArH), (m, 2H, ArH), 6.92 (ddd, 3JHH = 8.0 and 7.0 Hz, 4JHH =.3 Hz, H, 4-H), 6.74 (dd, 3 J HH = 8.0 Hz, 4 J HH =.3 Hz, H, 6-H), 5.65 (s, H, ),.83 (s, 6H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 55.3 (C-), 37.6 (C-9 ), 33.9 (C-2), 28.2 (ArH), 26.0 (ArH), 25.6 (ArC), 23.5 (ArC), 23.0 (ArH), 20.7 (ArH), 20.7 (ArH), 20.4 (ArH), 20.9 (ArH), 7.4 (ArH),.6 (ArH), 37. (C(CH 3 ) 2 ), 29.3 (CH 3 ). GC MS (EI) m/z (%): 25 (63, M + ), 236 (90, [M-CH 3 ] + ), 220 (), 58 (0), 7 (00, C 8 H 7 N + ), 9 (30, C 7 H 7+ ), 77 (7, C 6 H 5+ ). IR (ATR) ν /cm - : 333m (), 3034w, 2972w, 575w, 486m, 453m, 34wm, 285w, 22m, 54m, 05m, 040m, 02m, 967w, 830m, 767m, 747s (Ar), 62m. 32

33 f (ppm) f (ppm) 3ha 3ha

34 (E)-2-(-(H-indol-3-yl)but-2-en--yl)phenol (3ia) The compound 3ia was prepared according to the general procedure for hydroarylation from (E)-2-(buta-,3-dien--yl)phenol (7 mg, 487 µmol), indole (65 mg, 550 µmol) and diphenyl phosphate (6.3 mg, 25 µmol) at 80 C. The product was purified by column chromatography (silica, pentane/ethyl acetate 7: 5:) and obtained as colorless oil (69 mg, 54%). C 8 H 7 NO ( g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.82 (s, H), 7.66 (d, J = 8. Hz, H), 7.26 (s, 2H), (m, H), (m, 2H), 6.9 (dd, J = 2.3,. Hz, H), 6.82 (td, J = 7.5,.2 Hz, H), 6.70 (dd, J = 3.3,.2 Hz, H), 6.68 (s, H), 6.39 (ddd, J = 5.9, 7.0,.0 Hz, H), 5.03 (s, H), 3.9 (dq, J = 7.o, 2.3 Hz, H),.53 (d, J = 7.0 Hz, 3H). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 52.6 (C q ), 37.9 (CH), 36.7 (C q ), 28.2 (CH), 27.6 (CH), 26.8 (C q ), 25.0 (C q ), 22.5 (CH), 22. (CH), 2.0 (CH), 20.6 (CH), 20.3 (C q ), 9.6 (CH), 9.4 (CH), 5.8 (CH),.4 (CH), 34.8 (CH), 20.8 (CH 3 ). HRMS (EI) m/z (%): calculated for C 8 H 7 NO [M-H] ; found IR (ATR) ν /cm - : 3406 (m), 2964 (w), 499 (m), 455 (m), 337 (w), 096 (m), 8 (m), 737 (s). 34

35 f (ppm) f (ppm) 3ia 3ia

36 2-(-(H-Indol-3-yl)propyl)phenol (3ja) HO 2 3 3' 4 4' 5' 2' ' 9' 8' 6' 7' The compound 3ja was prepared according to a modified general procedure for hydroarylation from 2-(prop-2-enyl)phenol (67. mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (2.5 mg, 50.0 µmol) at 00 C. The product was purified by column chromatography (silica, heptane/ethyl acetate 85:5) and obtained as a purple oil (3 mg, 90%). C 7 H 7 NO (25.32 g/mol) R f = 0.9 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.04 (br. S, H, ), (m, H, 5 -H), 7.34 (ddd, 3 J HH = 8.2 Hz, 4 J HH = 0.9 Hz, 5 J HH = 0.8 Hz, H, 8 -H), 7.32 (dd, 3 J HH = 7.3 Hz, 4 J HH =.6 Hz, H, 3-H), (m, 3H, 7 -H, 5-H, 2 -H), 7.0 (ddd, 3 J HH = 8.0 and 6.0 Hz, 4 J HH =.0 Hz, H, 6 -H), 6.93 (ddd, 3 J HH = 7.5 and 7.3 Hz, 4 J HH =.3 Hz, H, 4-H), 6.80 (dd, 3 J HH = 7.8 Hz, 4 J HH =.3 Hz, H, 6-H), 5.20 (br. S, H, ), 4.26 (t, 3 J HH = 7.4 Hz, H, CHCH 2 ), (m, 2H, CHCH 2 ), (t, 3 J HH = 7.3 Hz, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 54.3 (C-), 36.9 (C-9 ), 30.3 (C-2), 29.2 (C-3), 27.6 (C-5), 27.0 (C-4 ), 22.6 (C-7 ), 2.4 (C-2 ), 20.8 (C-4), 9.8 (C-5 ), 9.6 (C-6 ), 8.6 (C-3 ), 6.5 (C-6),.3 (C-8 ), 39.6 (CHCH 2 ), 27.0 (CHCH 2 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 25 (22, M + ), 222 (00, [M-CH 2 CH 3 ] + ), 204 (4), 65 (6), 7 (0, C 8 H 7 N + ), 77 (3, C 6 H 5+ ). HRMS (EI) m/z (%): calculated for C 7 H 7 NO [M] ; found IR (ATR) ν /cm - : 3407m (), 3057w, 296w, 2929w, 287w, 583w, 487m, 453s, 337m, 27m, 095m, 038m, 00m, 907m, 845w, 799m, 737s (Ar). 36

37 f (ppm) f (ppm) HO 3ja HO 3ja

38 2-(-(H-indol-3-yl)ethyl)-4-(tert-butyl)phenol (3ka) The compound 3ka was prepared according to the general procedure for hydroarylation from 24-(tert-butyl)-2-vinylphenol (88.4 mg, 502 µmol), indole (65 mg, 550 µmol) and diphenyl phosphate (6.4 mg, 25 µmol) at 80 C. The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0) and obtained as a brownish solid (33 mg, 9%). C 20 H 23 NO (293.4 g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.03 (s, H), (m, 3H), (m, 2H), (m, 2H), 6.7 (d, J = 8.4 Hz, H), 5.03 (s, H), 4.49 (q, J = 7. Hz, H),.77 (d, J = 7. Hz, 3H),.33 (s, 9H). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 5.9 (C q ), 43.5 (C q ), 37. (C q ), 30.5 (C q ), 26.7 (C q ), 25.5 (C q ), 24.4 (CH), 22.7 (CH), 2.3 (CH), 9.8 (CH), 9.7 (CH), 9.7 (CH), 6.0 (CH),.4 (CH), 34.3 (C q ), 33.2 (CH), 3.8 (CH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 293 (4, M + ), 278 (4), 262 (7), 6 (6), 7 (00). HRMS (EI) m/z (%): calculated for C 20 H 23 NO [M] ; found IR (ATR) ν /cm - : 340 (w), 3346 (w), 2960 (w), 50 (m), 26 (m), 09 (m), 02 (m), 823 (m), 747 (s). 38

39 f (ppm) f (ppm) 3ka 3ka

40 2-(-(H-indol-3-yl)ethyl)-4-methylphenol (3la) The compound 3la was prepared according to the general procedure for hydroarylation from 4-(tert-butyl)-2-vinylphenol (88.4 mg, 502 µmol), indole (65 mg, 550 µmol) and diphenyl phosphate (6.4 mg, 25 µmol) at 80 C. The product was purified by column chromatography (silica, pentane/ethyl acetate 60:0) and obtained as a brownish solid (2 mg, 8%). H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.04 (s, H), 7.4 (dq, J = 8.0, 0.9 Hz, H), 7.36 (dt, J = 8.2,.0 Hz, H), 7.8 (ddd, J = 8.2, 7.0,.2 Hz, H), (m, 3H), 6.93 (dd, J = 7.9, 2.0 Hz, H), 6.67 (d, J = 8. Hz, H), 4.97 (s, H), 4.48 (q, J = 7.4 Hz, H), 2.29 (s, 3H),.73 (d, J = 7. Hz, 3H). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 5.9, 37., 3.2, 30.0, 29.0, 28., 26.8, 22.7, 2.3, 9.9, 9.8, 6.3,.3, 32.4, 20.9, HRMS (EI) m/z (%): calculated for C 7 H 7 NO [M-H] ; found IR (ATR) ν /cm - : 3406 (m), 2964 (w), 499 (m), 455 (m), 337 (w), 096 (m), 8 (m), 737 (s). 40

41 f (ppm) f (ppm) 3la 3la

42 Methyl 3-(-(H-indol-3-yl)ethyl)-4-hydroxybenzoate (3ma) MeOOC 3' ' 4 5' 6' 2' ' 9' 8' 7' The compound 3ma was prepared according to the general procedure for hydroarylation from methyl 4-hydroxy-3-vinylbenzoate (89. mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.3 mg, 25 µmol). The product was purified by column chromatography (silica, n-pentane/et 2 O 5:-:). The title compound was obtained as colorless solid (44 mg, 98%). C 8 H 7 NO 3 ( g/mol) R f = 0.09 (silica, EA/heptane :2). M.p.: 56 C H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.5 (s, H, ), 8.05 (d, 3 J HH =.8 Hz, H, 3-H), 7.85 (dd, 3 J HH = 8.4,.8 Hz, H, 5-H), 7.36 (dd, 3 J HH = 8.0,.2 Hz, H), 7.35 (dd, 3 J HH = 8.4,. Hz, H), 7.35 (m, 2H, ArH), 7.9 (ddd, 3 J HH = 8.4, 7.0,.2 Hz, H), 7.07 (s, H, 2 -H), 7.02 (ddd, 3 J HH = 8.0, 7.0,. Hz, H), 6.79 (d, 3 J HH = 8.4 Hz, H, 6-H), 6.00 (s, H, ), 4.56 (q, 3 J HH = 7. Hz, H, CHCH 3 ), 3.90 (s, 3H, CO 2 CH 3 ),.75 (d, 3 J HH = 7. Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 67.5 (C q ), 58.7 (C q ), 37. (C q ), 3.5 (C q ), 30.5 (ArH), 29.9 (ArH), 26.5 (C q ), 22.8 (ArH), 22.7 (ArH), 2.4 (ArH), 9.9 (ArH), 9.6 (ArH), 8.9 (C q ), 6.4 (ArH),.5 (ArH), 52. (CO 2 CH 3 ), 32.3 (CHCH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 295 (6, M + ), 280 (00), 264 (7), 220 (3), 9 (9), 7 (82). HRMS (EI) m/z (%): calculated for C 8 H 7 O 3 N [M-H] ; found IR (ATR) ν /cm - : 3373 (m, ), 683 (s), 603 (m), 428 (m), 230 (s), 249 (m), 33 (w), 097 (w), 992 (w), 748 (s). 42

43 f (ppm) f (ppm) MeOOC 3ma MeOOC 3ma

44 2-(-(H-Indol-3-yl)ethyl)-4-nitrophenol (3na) NO 2 The compound 3na was prepared according to the general procedure for hydroarylation from 4-nitro-2-vinylphenol (82.6 mg, 500 µmol), indole (64.4 mg, 550 µmol) and diphenyl phosphate (6.3 mg, 25 µmol). The product was purified by column chromatography (silica, n- pentane/et 2 O 7:-5:). The title compound was obtained as colorless solid (85 mg, 63%). C 6 H 4 N 2 O 3 ( g/mol) M.p.: decomposition >200 C H NMR (300 MHz, d 4 -MeOD) δ/ppm: 7.90 (dd, J = 8.9, 2.9 Hz, H), 7.78 (d, J = 2.8 Hz, H), 7.32 (dt, J = 8.2, 0.9 Hz, H), (m, 2H), 7.02 (ddd, J = 8.2, 6.9,.2 Hz, H), 6.90 (d, J = 8.9 Hz, H), 6.84 (ddd, J = 8.0, 7.0,.0 Hz, H), 4.79 (q, J = 7. Hz, H),.62 (d, J = 7. Hz, 3H). 3 C NMR (75 MHz, d 4 -MeOD) δ/ppm: 62. (C q ), 4.8 (C q ), 38.5 (C q ), 36.5 (C q ), 27.9 (C q ), 25.3 (CH), 24.(CH), 22.9 (CH), 22.4 (CH), 9.9 (C q ), 9.8 (CH), 9.5 (CH), 5.7 (CH), 2.2 (CH), 30.5 (CH), 20.9 (CH 3 ). GC MS (EI) m/z (%): 282 (64, M + ), 267 (00, [M] + ), 264 (7), 22 (22), 9 (), 44 (4), 7 (75). HRMS (EI) m/z (%): calculated for C 6 H 4 O 3 N 2 [M-H] ; found IR (ATR) ν /cm - : 343 (w), 2534 (m), 583 (m), 48 (m), 324 (s), 272 (s), 082 (m), 905 (m), 74 (s), 639 (m). 44

45 f (ppm) f (ppm) NO 2 3na NO 2 3na

46 2-(-(5-Chloro-H-indol-3-yl)ethyl)phenol (3ab) Cl The compound 3ab was prepared according to the modified general procedure for hydroarylation from 2-vinylphenol (60 mg, 500 µmol), 5-chloroindole (84.4 mg, 550 µmol) and diphenyl phosphate (2.6 mg, 60 µmol) in DCE at 00 C. The product was purified by column chromatography (silica, n-pentane/et 2 O 7:-5:). The title compound was obtained as colorless solid (85 mg, 63%). C 6 H 4 ClNO (27.74 g/mol) M.p.: 25 C H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.03 (s, H, ), 7.38 (ddd, J =.9, 0.6 Hz, H), 7.26 (dd, J = 7.5,.7 Hz, H), 7.2 (dd, J = 8.6, 0.6 Hz, H), (m, 2H), 7.03 (dd, J = 2.4, 0.9 Hz, H), 6.95 (ddd, J = 7.5,.2 Hz, H), 6.79 (dd, J = 8.0,.2 Hz, H), 5.9 (s, H, ), 4.53 (q, J = 7. Hz, H, CH),.72 (d, J = 7. Hz, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 53.6 (C q ), 35.3 (C q ), 3.4 (C q ), 28.4 (ArH), 27.8 (C q ), 27.7 (ArH), 25.3 (C q ), 22.9 (ArH), 22.7 (ArH), 2. (ArH), 9.7 (C q ), 9.2 (ArH), 6.3 (ArH), 2.4 (ArH), 3.5 (CHCH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 27 (68, M + ), 256 (99), 220 (23), 65 (2), 5 (00), 5 (0), 9 (5). HRMS (EI) m/z (%): calculated for C 6 H 4 ClNO [M-H] ; found IR (ATR) ν /cm - : 347 (m, ), 589 (w), 45 (m), 327 (w), 27 (m), 097 (m), 906 (m), 838 (w), 796 (s), 75 (s), 728 (s), 584 (m). 46

47 f (ppm) f (ppm) ab Cl 3ab Cl

48 2-(-(5-Bromo-H-indol-3-yl)ethyl)phenol (3ac) 6 5 2' 2 3' ' 3a 3 4' 4 Br 5' 7a 7' 6' The compound 3ac was prepared according to a modified general procedure for hydroarylation from 2-vinylphenol (60 mg, 500 µmol), 5-bromoindole (08 mg, 550 µmol) and diphenyl phosphate (2.6 mg, 60 µmol) in DCE at 00 C. The product was purified by column chromatography (silica, n-pentane/et 2 O 7:-5:). The title compound was obtained as colorless solid (82 mg, 52%). C 6 H 4 BrNO (36.20 g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.03 (s, H, ), 7.38 (ddd, J =.9, 0.6 Hz, H), 7.26 (dd, J = 7.5,.7 Hz, H), 7.2 (dd, J = 8.6, 0.6 Hz, H), (m, 2H), 7.03 (dd, J = 2.4, 0.9 Hz, H), 6.95 (ddd, J = 7.5,.2 Hz, H), 6.79 (dd, J = 8.0,.2 Hz, H), 5.9 (s, H, ), 4.53 (q, J = 7. Hz, H, CH),.72 (d, J = 7. Hz, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 53.6 (C q ), 35.3 (C q ), 3.4 (C q ), 28.4 (ArH), 27.8 (C q ), 27.7 (ArH), 25.3 (C q ), 22.9 (ArH), 22.7 (ArH), 2. (ArH), 9.7 (C q ), 9.2 (ArH), 6.3 (ArH), 2.4 (ArH), 3.5 (CHCH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 35 (7, M + ), 300 (93), 220 (69), 97 (00), 65 (8), 43 (2), 6 (27), 9 (24). HRMS (EI) m/z (%): calculated for C 6 H 4 BrNO [M+H] ; found IR (ATR) ν /cm - : 348 (m, ), 590 (w), 453 (s), 327 (w), 220 (m), 097 (m), 796 (m), 753 (s). 48

49 f (ppm) f (ppm) 3ac Br 3ac Br

50 2-(-(5-Iodo-H-indol-3-yl)ethyl)phenol (3ad) I The compound 3ad was prepared according to a modified general procedure for hydroarylation from 2-vinylphenol (60 mg, 500 µmol), 5-iodoindole (33.8 mg, 550 µmol) and diphenyl phosphate (2.6 mg, 60 µmol) in DCE at 00 C. The product was purified by column chromatography (silica, n-pentane/et 2 O 7:-5:). The title compound was obtained as reddish oil (05 mg, 58%). C 6 H 4 INO ( g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.03 (s, H, ), 7.38 (ddd, J =.9, 0.6 Hz, H), 7.26 (dd, J = 7.5,.7 Hz, H), 7.2 (dd, J = 8.6, 0.6 Hz, H), (m, 2H), 7.03 (dd, J = 2.4, 0.9 Hz, H), 6.95 (ddd, J = 7.5,.2 Hz, H), 6.79 (dd, J = 8.0,.2 Hz, H), 5.9 (s, H, ), 4.53 (q, J = 7. Hz, H, CH),.72 (d, J = 7. Hz, 3H, CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 53.6 (C q ), 35.3 (C q ), 3.4 (C q ), 28.4 (ArH), 27.8 (C q ), 27.7 (ArH), 25.3 (C q ), 22.9 (ArH), 22.7 (ArH), 2. (ArH), 9.7 (C q ), 9.2 (ArH), 6.3 (ArH), 2.4 (ArH), 3.5 (CHCH 3 ), 20.4 (CH 3 ). GC MS (EI) m/z (%): 35 (7, M + ), 300 (93), 220 (69), 97 (00), 65 (8), 43 (2), 6 (27), 9 (24). HRMS (EI) m/z (%): calculated for C 6 H 4 INO [M+H] ; found IR (ATR) ν /cm - : 348 (m, ), 590 (w), 453 (s), 327 (w), 220 (m), 097 (m), 796 (m), 753 (s). 50

51 f (ppm) f (ppm) 3ad I 3ad I

52 2-(-(-Methyl-H-indol-3-yl)ethyl)phenol (3ae) N The compound 3ea was prepared according to the general procedure for hydroarylation from 2-vinylphenol (60. mg, 500 µmol), -methylindole (72. mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 95:5) and obtained as yellow oil (0 mg, 80%). The analytical data were in accordance with the literature. 3 C 7 H 7 NO (25.33 g/mol) R f = 0.32 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.4 (ddd, 3 J HH = 8.0 Hz, 4 J HH = 0.9 Hz, 5 J HH =.0 Hz, H), (m, 2H), (m, 2H), (m, 3H), 6.82 (dd, 3 J HH = 8.0 Hz, 4 J HH =.2 Hz, H), 5.20 (br. S, H, ), 4.5 (q, 3 J HH = 7. Hz, H, CHCH 3 ), 3.76 (s, 3H, CH 3 ),.74 (d, 3 J HH = 7. Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 54.2 (C q ), 37.7 (C q ), 3.5 (C q ), 28.2 (ArH), 27.6 (ArH), 27.0 (C q ), 26.0 (ArH), 22.2 (ArH), 20.8 (ArH), 9.8 (ArH), 9. (ArH), 7.7 (C q ), 6.4 (ArH), 09.4 (ArH), 32.8 (CH 3 ), 32.3 (CHCH 3 ), 20.4 (CHCH 3 ). GC MS (EI) m/z (%): 25 (9, M + ), 236 (83, [M-CH 3 ] + ), 220 (22), 65 (25), 3 (00, C 9 H 0 N + ), 9 (5, C 7 H 7+ ), 77 (33, C 6 H 5+ ), 63 (24), 5 (2). 52

53 N 3ae N 3ae 53

54 2-(-(2-Methyl-H-indol-3-yl)ethyl)phenol (3af) The compound 3af was prepared according to the general procedure for hydroarylation from 2-vinylphenol (60. mg, 500 µmol), 2-methylindole (72. mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0) and obtained as orange oil (87 mg, 69%). The analytical data were in accordance with the literature. 3 C 7 H 7 NO (25.33 g/mol) R f = 0.23 (silica, EA/heptane :4). H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.88 (br.s, H, ), 7.56 (dd, 3 J HH = 7.7 Hz, H), 7.35 (dd, 3 J HH = 8.0 Hz, H), (m, 5H), 6.8 (dd, 3 J HH = 8.0 Hz, 4 J HH =.2 Hz, H), 5.26 (br. S, H, ), 4.5 (q, 3 J HH = 7.2 Hz, H, CHCH 3 ), 2.34 (s, 3H, CH 3 ),.77 (d, 3 J HH = 7.2 Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 54.7 (C q ), 35.5 (C q ), 3.6 (C q ), 30.8 (C q ), 27.6 (ArH), 27. (C q ), 26.9 (ArH), 2.5 (ArH), 20.6 (ArH), 9.6 (ArH), 8.7 (ArH), 6.2 (ArH), 2.7 (C q ), 0.5 (ArH), 30.4 (CHCH 3 ), 9.7 (CHCH 3 ), 2.0 (CH 3 ). GC MS (EI) m/z (%): 25 (49, M + ), 236 (60, [M-CH 3 ] + ), 65 (9), 3 (00, C 9 H 0 N + ), 9 (2, C 7 H 7+ ), 77 (5, C 6 H 5+ ), 63 (2), 5 (0). 54

55 3af 3af 55

56 Ethyl 3-(-(2-hydroxyphenyl)ethyl)-H-indole-2-carboxylate (3ag) The compound 3ag was prepared according to the general procedure for hydroarylation from 2-vinylphenol (60. mg, 500 µmol), ethyl H-indole-2-carboxylate (04. mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0) and obtained as orange oil ( mg, 72%). The analytical data were in accordance with the literature. 3 C 9 H 9 NO 3 ( g/mol) R f = 0.20 (silica, EA/heptane :4). M.p.: C H NMR (300 MHz, CDCl 3 ) δ/ppm: 8.87 (br. S, H, ), 7.84 (ddd, 3 J HH = 8.2 Hz, 4 J HH = 0.9 Hz, 5 J HH = 0.8 Hz, H), 7.77 (dd, 3 J HH = 7.70 Hz, 4 J HH =.6Hz, H), 7.5 (br. s, H, ), 7.40 (dd, 3 J HH = 8.3 Hz, 4 J HH = 0.9 and 0.9 Hz, H), (m, H), 7.8 (ddd, 3 J HH = 7.6 and 7.7 Hz, 4 J HH =.6 Hz, H), (m, 2H), 6.92 (dd, 3 J HH = 8.0 Hz, 4 J HH =.6 Hz, H), 5.39 (q, 3 J HH = 7.2 Hz, H, CHCH 3 ), 4.27 and 3.95 (ABX, 2H, CH 2 CH 3 ),.92 (d, 3 J HH = 7.2 Hz, 3H, CHCH 3 ),.2 (t, 3 J HH = 7.2 Hz, 3H, CH 2 CH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 63.8 (COOEt), 54.9 (C q ), 36.5 (C q ), 29.3 (C q ), 27.7 (ArH), 27.5 (C q ), 26.8 (ArH), 26.0 (C q ), 25.7 (ArH), 22.6 (ArH), 2.4 (C q ), 20.9 (ArH), 20.6 (ArH), 6.4 (ArH), 2.4 (ArH), 6.7 (CH 2 CH 3 ), 29.6 (CHCH 3 ), 9.7 (CH 3 ), 4.0 (CH 3 ). GC MS (EI) m/z (%): 263 (5, [M-OEt] + ), 248 (00, [M-OEt-] + ), 220 (62, [M-COOEt- ] + ), 204 (9), 9 (5), 65 (9), 5 (6, C 8 H 5 N + ), 89 (6), 77 (6, C 6 H 5+ ), 63 (0), 5 (7). 56

57 57

58 2-(-(2,4,6-Trimethoxyphenyl)ethyl)phenol (6aa) The compound 6aa was prepared according to the general procedure for hydroarylation from 2-vinylphenol (60. mg, 500 µmol),,3,5-trimethoxyphenol (92.5 mg, 550 µmol) and diphenyl phosphate (6.2 mg, 25 µmol). The product was purified by column chromatography (silica, heptane/ethyl acetate 95:5-90:0) and obtained as yellow solid (82 mg, 57%) MeO 2 ' 2' OMe 4' 3' OMe C 7 H 20 O 4 ( g/mol) R f = 0.24 (silica, EA/heptane :4). M.p.: 4-5 C H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.53 (dd, 3 J HH = 7.7 Hz, 4 J HH =.3 Hz, H, 3-H), 7.08 (ddd, 3 J HH = 8.0 and 7.5 Hz, 4 J HH =.3 Hz, H, 5-H), 6.88 (ddd, 3 J HH = 7.7 and 7.5 Hz, 4 J HH =.3 Hz, H, 4-H), 6.79 (dd, 3 J HH = 8.0 Hz, 4 J HH =.3 Hz, H, 6-H), 6.7 (s, H, ), 6.4 (s, 2H, 3 -H), 4.65 (q, 3 J HH = 7.2 Hz, H, CHCH 3 ), 3.82 (s, 6H, 2 -OCH 3 ), 3.77 (s, 3H, 4 -OCH 3 ),.73 (d, 3 J HH = 7.2 Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 60.0 (C-2 ), 58.4 (C-4 ), 54.5 (C-), 30.0 (C-2), 28.4 (C-3), 27.0 (C-5), 9.5 (C-4), 5.5 (C-6), 2.8 (C- ), 9.8 (C-3 ), 56.0 (2 -OCH 3 ), 55.4 (4 -OCH 3 ), 27.8 (CHCH 3 ), 7.3 (CH 3 ). GC MS (EI) m/z (%): 288 (24, M + ), 204 (5), 68 (00, C 9 H 2 O 3+ ), 39 (2), 2 (5), 07 (4), 9 (7, C 7 H 7+ ), 77 (5, C 6 H 5+ ), 5 (2), 39 (2). HRMS (EI) m/z (%): calculated for C 7 H 2 O 4 [M+H] ; found IR (ATR) ν /cm - : 340m (), 3003w, 2943w, 2844w, 606m, 586s, 485m, 463m, 420m, 350w, 37w, 230m, 204s, 47s, 4s, 098s, 027m, 945m, 820m, 807m, 759s, 632m. 58

59 f (ppm) f (ppm) OMe MeO OMe 6aa OMe MeO OMe 6aa

60 4-(-(2,4,6-Trimethoxyphenyl)ethyl)phenol (6ca) HO MeO OMe OMe The compound 6ca was prepared according to a modified general procedure for hydroarylation from freshly prepared 4-vinylphenol (60 mg, 5.00 mmol),,3,5- trimethoxyphenol (.68 g, 0.0 mmol) and diphenyl phosphate (62. mg, 250 µmol) at 00 C in DCE. The product was purified by column chromatography (silica, heptane/ethyl acetate 90:0-80:20) and obtained as colorless solid (.3 g, 9%). C 7 H 20 O 4 ( g/mol) R f = 0.2 (silica, EA/heptane :4). M.p.: 6-7 C H NMR (300 MHz, CDCl 3 ) δ/ppm: 7.5 (d, 3 J HH = 8.6 Hz, 2H, 3-H), 6.69 (d, 3 J HH = 8.6 Hz, 2H, 2-H), 6.4 (s, 2H, 3 -H), 4.69 (q and br. s, 3 J HH = 7.3 Hz, 2H,, CHCH 3 ), 3.80 (s, 3H, 4 -OCH 3 ), 3.70 (s, 6H, 2 -OCH 3 ),.62 (d, 3 J HH = 7.3 Hz, 3H, CHCH 3 ). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 59.4 (C-4 ), 59. (C-2 ), 52.9 (C-), 39. (C-4), 28.5 (C-3), 6.2 (C- ), 4.5 (C-2), 9.6 (C-3 ), 55.9 (2 -OCH 3 ), 55.4 (4 -OCH 3 ), 32.4 (CHCH 3 ), 8.2 (CH 3 ). GC MS (EI) m/z (%): 288 (4, M + ), 273 (00, [M-CH 3 ] + ), 67 (00, C 9 H O 3+ ), 37 (6), 07 (5), 9 (5, C 7 H 7+ ), 77 (5, C 6 H 5+ ). HRMS (EI) m/z (%): calculated for C 7 H 2 O 4 [M+H] ; found IR (ATR) ν /cm - : 3372m (), 2998w, 2938m, 2837w, 585m, 5m, 489w, 455m, 40m, 350w, 256w, 29m, 98m, 22s, 063m, 037m, 939m, 835m, 80m, 778m, 629m. 60

61 f (ppm) f (ppm) OMe MeO OMe 6ba HO OMe MeO OMe 6ba HO

62 6-(-(2,4,6-Trimethoxyphenyl)ethyl)naphthalen-2-ol (6da) HO MeO OMe OMe The compound 6da was prepared according to the modified general procedure for hydroarylation from 6-vinylnaphthalyl-2-ol (85. mg, 500 µmol),,3,5-trimethoxyphenol (68 mg, mmol) and diphenyl phosphate (2.4 mg, 50 µmol, 0 mol%) at 00 C in DCE. The product was purified by column chromatography (silica, n-pentane/ethyl acetate 5:-4:) and obtained as colorless solid (02 mg, 60%). C 2 H 22 O 4 ( g/mol) H NMR (300 MHz, CDCl 3 ) δ/ppm: (m, 2H), 7.5 (d, J = 8.5 Hz, H), 7.38 (dd, J = 8.5,.8 Hz, H), (m, 2H), 6.9 (s, 2H), 5.44 (s, H), 4.9 (q, J = 7.2 Hz, H), 3.83 (s, 3H), 3.70 (s, 6H),.77 (d, J = 7.2 Hz, 3H). 3 C NMR (75 MHz, CDCl 3 ) δ/ppm: 59.5 (C q ), 59.2 (C q ), 52.7 (C q ), 4.9 (C q ), 32.7 (C q ), 29.6 (CH), 29.0 (C q ), 27.8 (CH), 25.5 (CH), 24.7 (CH), 7.3 (CH), 6.0 (C q ), 09.3 (CH), 9.7 (CH), 55.9 (OCH 3 ), 55.4 (OCH 3 ), 33.0 (CH), 7.9 (CH 3 ). GC MS (EI) m/z (%): 338 (53, M + ), 323 (00, [M-CH 3 ] + ), 307 (6), 95 (5), 67 (2), 57 (37), 5 (4). HRMS (EI) m/z (%): calculated for C 2 H 23 O 4 [M+H] ; found IR (ATR) ν /cm - : 334m (), 2963w, 2936m, 2834w, 588m, 435m, 97w, 7m, 03m, 938w, 89w, 587m, 822m, 659m, 606w, 469s. 62

63 f (ppm) f (ppm) HO OMe MeO OMe 6da HO OMe MeO OMe 6da

64 Purification of Laboratory Chemicals (Eds: Perrin, D. D.; Armarego, W. L. F.). Pergamon Press, Oxford, 988 (3). 2 Konishi, H.; Ueda, T.; Muto, T.; Manabe, K. Org. Lett. 202, 4, Pathak, T. P.; Sigman, M. S. Org. Lett. 20, 3, Pearson, E. L.; L. C. H. Kwan, C. I. Turner, G. A. Jones, A. C. Willis, M. N. Paddon-Row, M. S. Sherburn, J. Org. Chem. 2006, 7, L. Pérez-Serrano, J. Blanco-Urgoiti, L. Casarrubios, G. Domínguez, J. Pérez-Castells, J. Org. Chem. 2000, 65,