7 Experimental Section
7.2 Experimental details for Chapter 2
Synthesis of [Pd(IHept)(acac)Cl] 20
IHept•HCl (520 mg 0.80 mmol, 1.2 eq.) and [Pd(acac)2] (192 mg, 0. 64 mmol, 1 eq.) were
added in a dry Schlenk flask equipped with a stirring bar. They were purged three time with vacuum/ nitrogen cycles, and then dry 1,4-dioxane (10 ml) was added under a nitrogen atmosphere. The reaction mixture was refluxed overnight. The solvent was evaporated and the crude was dissolved in pentane. The solution was filtered through a pad of silica covered with Celite, washing with pentane. After evaporation of the solvent and drying under high vacuum, the pure desired complex was obtained as a yellow powder (432 mg, 81%).
General procedure for the α-arylation of ketones using pre-catalyst 20
Inside a glovebox, a vial containing a stir bar was charged with NaOtBu (105 mg, 1.1 mmol, 2.2 equivalents), Solid ketones (0.7 mmol, 1.4 equivalents) and/or aryl chlorides (0.50 mmol, 1.0 equivalents) were added at this point and dissolved in toluene, and the vial was sealed. A stock solution of 20 [Pd(IHept)(acac)Cl] in toluene was prepared and dispensed with a syringe (e.g.: 4.3 mg in 2 mL. 0.1 mL of this solution correspond to 500 ppm catalyst loading. Total reaction volume was 1 mL). Outside of the glovebox, ketone and/or the aryl chloride were added if liquids, followed by the stock solution. Finally, the vial was stirred at 600 rpm, at T= 100 °C for 16 hours. The solution was then cooled to room temperature, some drops of water were added and the crude was filtered through silica eluting with ethyl acetate. The organic layers were dried under vaccum. Column chromatography of the crude (typically hexane/ethyl acetate 9/1) gave the desired product.
prepared in a second vial (2.6 mg in 2 mL of dry toluene). Propiophenone (90 µL, 91 mg, 0.68 mmol, 1.36 eq.), 2-Cl-anisole (71 mg, 0.5 mmol, 1 eq.) and 0.1 mL of the stock solution (corresponding to 300 ppm) were added to the vial containing the base. The vial was then sealed and magnetically stirred at 100°C overnight. The workup reported above afforded 181 mg (75%) of the desired product.
Characterisation data 20 [Pd(IHept)(acac)Cl] 1H NMR (300 MHz, CDCl3): δ 7.36 (t, J = 7.8 Hz, 2H), 7.21 (d, J = 7.8 Hz, 4H), 7.02 (s, 2H), 4.98 (s, 1H), 2.82 (m, 4H), 2.17 (m, 4H), 1.77 (s, 3H), 1.40 (s, 3H), 1.73-1.25 (m, 20H), 1.15-1.08 (m, 8H), 0.80 (t, J = 7.1 Hz, 24H). 13C NMR (75 MHz, CDCl3): δ 186.4, 184.1, 154.4, 144.8, 137.0, 129.3, 125.3, 125.6, 99.9, 40.0, 39.9, 39.1, 26.9, 26.0, 21.7, 21.2, 15.14.
Anal. Calcd for C48H75ClN2O2Pd: C, 67.51; H, 8.85; N, 3.28. Found: C, 67.39; H, 8.77; N,
3.39.
29. 1-Phenyl-2-(p-tolyl)ethan-1-one:3
Pd loading 0.02 mol%. Yield 80%, 176 mg, yellow oil.
1H NMR (500 MHz, CDCl3): δ 8.03-8.01 (m, 2H), 7.57-7.55 (m, 1H), 7.48-7.44 (m, 2H),
7.18-7.13 (m, 4H), 4.26 (s, 2H), 2.33 (s, 3H).
13C NMR (125 MHz, CDCl3): δ 197.8, 136.4, 133.1, 131.4, 129.4, 129.3, 128.6, 45.1, 21.0.
Analytical data matches previously reported characterisation. 30. 1-(4-Methoxyphenyl)-2-(p-tolyl)ethan-1-one:3
Pd loading 0.05 mol%. Yield 70%, 168 mg, white solid.
1H NMR (500 MHz, CDCl3): δ 7.97-7.94 (m, 2H), 7.49-7.45 (m, 1H), 7.40-7.36 (m, 2H),
7.22-7.19 (m, 2H), 6.85-6.82 (m, 2H), 4.65 (q, J= 6.8Hz, 1H), 3.88 (s, 3H), 1.51 (d, J= 7.8Hz, 3H).
13C NMR (125 MHz, CDCl3): δ 200.5, 158.4, 136.6, 133.4, 132.7, 128.7, 128.7, 128.4, 114.3,
55.2, 46.9, 19.5.
Analytical data matches previously reported characterisation.
O
O
31. 2-(p-Tolyl)-1-(4-(trifluoromethyl)phenyl)ethan-1- one:4
Pd loading 0.2 mol%. Yield 82%, 228 mg, pale yellow solid.
1H NMR (500 MHz, CDCl3): δ 8.10 (d, J= 8.2 Hz, 2H), 7.71 (d, J= 8.3 Hz, 2H), 7.15 (s,
4H), 4.27 (s, 2H), 2.33 (s, 3H).
13C NMR (125 MHz, CDCl3): δ 196.8, 139.2, 136.8, 134.3 (q, JCF= 32.6 Hz), 130.6, 129.5,
129.2, 128.9, 125.7 (q, JCF= 3.5 Hz), 123.5 (q, JCF= 272.7 Hz), 45.5, 21.1. 19F NMR (471 MHz, CDCl3): δ -63.1
Analytical data matches previously reported characterisation. 32. 1-Mesityl-2-(4-methoxyphenyl)ethan-1-one:
Pd loading 0.05 mol%. Yield 84%, 225 mg.
1H NMR (500 MHz, CDCl3): δ 7.13 (d, J= 8.6 Hz, 2H), 6.87 (d, J= 8.6 Hz, 2H), 6.84 (s,
2H), 3.95 (s, 2H), 3.80 (s, 3H), 2.29 (s, 3H), 2.14 (s, 6H).
13C NMR (125 MHz, CDCl3): δ 207.9, 158.6, 139.1, 138.4, 132.7, 130.8, 128.4, 125.2, 113.9,
55.2, 50.8, 21.0, 19.1.
HRMS: Calculated for C18H20O2: 269.1542, Found: [M+H]+ 269.1536
33. 2-(2,6-Dimethylphenyl)-1-phenylethan-1-one:3
Pd loading 0.03 mol%. Yield 89%, 200 mg, colourless oil.
1H NMR (500 MHz, CDCl3): δ 8.09 (d, J= 8.1 Hz, 2H), 7.62 (t, J= 7.4 Hz, 1H), 7.52 (t, J=
7.2 Hz, 2H), 7.14-7.06 (m, 3H), 4.39 (s, 2H), 2.23 (s, 3H).
13C NMR (125 MHz, CDCl3): δ 196.9, 137.1, 137.0, 133.2, 132.4, 128.7, 128.1, 128.0, 126.9,
39.6, 20.4.
Analytical data matches previously reported characterisation. 34. 2-(2,6-Dimethylphenyl)-1-(4-methoxyphenyl)ethan-1-one:3
Pd loading 0.02 mol%. Yield 87%, 222 mg, white solid.
1H NMR (400 MHz, CDCl3): δ 8.09-8.04 (m, 2H), 7.12-7.04 (m, 3H), 7.00-6.96 (m, 2H), 4.33 (s, 2H), 3.90 (s, 3H), 2.22 (s, 6H). O F3C O OMe O O MeO
Analytical data matches previously reported characterisation. 35. 2-(2,6-Dimethylphenyl)-1-(3-methoxyphenyl)ethanone:5
Pd loading 0.05 mol%. Yield 92%, yellow oil.
1H NMR (500 MHz, CDCl3): δ 7.71 (d, J=7.6 Hz, 1H), 7.60 (br s, 1H), 7.45 (t, J=7.9 Hz,
1H), 7.17 (dd, J=8.2 Hz, J= 2.2 Hz), 7.15-7.12 (m, 1H), 7.10-7.08 (m, 2H), 4.38 (s, 2H), 3.89 (s, 3H), 2.24 (s, 6H).
13C NMR (125 MHz, CDCl3): δ 196.7, 159.8, 138.4, 136.9, 132.4, 129.6, 127.9, 126.9, 120.6,
119.5, 112.4, 55.4, 21.0, 39.7, 20.3.
Analytical data matches previously reported characterisation. 36. 1,2-Di-(2-methylphenyl)ethanone:6
Pd loading 0.05 mol%. Yield 98%, 221 mg, colourless oil.
1H NMR (500 MHz, CDCl3): δ 7.74 (d, J= 7.5 Hz, 1H), 7.39 (dt, J1= 7.5 Hz, J2 = 1Hz, 1H),
7.29-7.24 (m, 2H), 7.21-7.11 (m, 4H), 4.24 (s, 2H), 2.46 (s, 3H), 2.27 (s, 3H).
13C NMR (125 MHz, CDCl3): δ 201.3, 138.3, 137.8, 136.8, 133.3, 132.0, 131.3, 130.5, 130.3,
128.4, 127.2, 126.1, 125.6, 46.4 21.2, 19.8.
Analytical data matches previously reported characterisation. 37. 1-(6-Methoxynaphthalen-2-yl)-2-(p-tolyl)ethan-1-one:
Pd loading 0.05 mol%. Yield 87%, 254 mg.
1H NMR (400 MHz, CDCl3): δ 8.47 (d, J= 1.5 Hz, 1H), 8.04 (dd, J= 8.6 Hz, J= 1.6 Hz, 1H),
7.85 (d, J= 9.0 Hz, 1H), 7.76 (d, J= 8.7 Hz, 1H), 7.22-7.18 (m, 3H), 7.15-7.12 (m, 3H), 4.35 (s, 2H), 3.95 (s, 3H), 2.32 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 197.8, 159.9, 137.4, 136.6, 132.2, 131.9, 131.3, 130.4, 129.5,
129.4, 128.0, 127.3, 125.2, 119.8, 105.9, 55.6, 45.2, 21.2.
HRMS: Calculated for C20H18O2: 291.1385, Found: [M+H]+ = 291.1382
38. 2-(2-Methoxyphenyl)-1-phenylpropan-1-one:3
Pd loading 0.03 mol%. Yield 91%, 218 mg, yellow oil. When performed in air, yield 75%, 179 mg.
O MeO O O MeO O OMe
1H NMR (500 MHz, CDCl3): δ 7.99-7.94 (m, 2H), 7.47-7.42 (m, 1H), 7.37-7.34 (m, 2H),
7.18 (td, J= 8Hz, J= 1.7 Hz, 1H), 7.12 (dd, J= 8Hz, J= 1.6 Hz, 1H), 6.88 (d, J= 7.8Hz, 2H), 5.09 (q, J= 6.8Hz, 1H), 3.88 (s, 3H), 1.47 (d, J= 7.8Hz, 3H).
13C NMR (125 MHz, CDCl3): δ 201.3, 155.7, 136.4, 132.5, 130.1, 128.4, 128.2, 128.0, 127.9,
120.9, 110.7, 55.4, 40.3, 17.5.
Analytical data matches previously reported characterisation. 39. 2-(4-Methoxyphenyl)-1-phenylpropan-1-one:3
Pd loading 0.03 mol%. Yield 97%, 233 mg, yellow solid.
1H NMR (500 MHz, CDCl3): δ 7.97-7.94 (m, 2H), 7.49-7.45 (m, 1H), 7.40-7.36 (m, 2H),
7.22-7.19 (m, 2H), 6.85-6.82 (m, 2H), 4.65 (q, J= 6.8Hz, 1H), 3.88 (s, 3H), 1.51 (d, J= 7.8Hz, 3H).
13C NMR (125 MHz, CDCl3): δ 200.5, 158.4, 136.6, 133.4, 132.7 , 128.7, 128.7, 128.4, 114.3,
55.2, 46.9, 19.5.
Analytical data matches previously reported characterisation. 40. 1-(6-Methylpyridin-3-yl)-2-(p-tolyl)ethan-1-one:
Pd loading 0.05 mol%. Yield 80%, 180 mg, brown oil.
1H NMR (400 MHz, CDCl3): δ 9.10 (d, J= 2.0 Hz, 1H), 8.13 (dd, J= 8.1 Hz, J= 2.3 Hz, 1H),
7.22 (d, J= 8.1 Hz, 1H), 7.16-7.10 (m, 4H), 4.21 (s, 2H), 2.60 (s, 3H), 2.30 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 196.5, 163.3, 149.9, 136.8, 136.3, 130.8, 129.6, 129.4, 129.3,
123.4, 45.5, 24.9, 21.1.
HRMS: Calculated for C15H15NO: 226.1231, Found: [M+H]+ = 226.1225
41. 1-Phenyl-2-(thiophen-3-yl)propan-1-one: 7
Pd loading 0.05 mol%. Yield 84%, 182 mg, brown oil.
1H NMR (400 MHz, CDCl3): δ 7.88-7.85 (m, 2H), 7.42-7.35 (m, 1H), 7.33-7.26 (m, 2H), 7.13 (dd, J= 4.9 Hz, J= 2.9 Hz, 1H), 6.99 -6.96 (m, 1H), 6.91 (dd, J= 5.0 Hz, J= 1.4 Hz, 1H), 4.74 (q, J= 6.9 Hz, 1H), 1.43 (d, J= 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 200.0, 141.3, 136.2, 132.8, 128.6, 128.4, 127.0, 126.0, 121.3, 42.7, 18.8. O OMe N O O S
42. 1-Phenyl-2-(pyridin-3-yl)propan-1-one:3
Pd loading 0.05 mol%. Yield 96%, 202 mg, brown oil.
1H NMR (400 MHz, CDCl3): δ 8.60 (d, J= 2.0 Hz, 1H), 8.46 (dd, J= 4.8 Hz, J= 1.6 Hz, 1H),
7.96-7.93 (m, 2H), 7.60 (dt, J= 7.9 Hz, J= 1.9 Hz, 1H), 7.54-7.49 (m, 1H), 7.43-7.38 (m, 2H), 4.74 (q, J= 6.9 Hz, 1H), 1.56 (d, J= 6.9 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 199.7, 149.6, 148.5, 137.0, 136.0, 135.2, 133.4, 128.8, 128.8,
123.9, 45.0, 19.5.
Analytical data matches previously reported characterisation. 43. 1-Phenyl-2-(4-(trifluoromethyl)phenyl)propan-1-one:3
Pd loading 0.05 mol%. Yield 81%, 225 mg, brown solid.
1H NMR (400 MHz, CDCl3): δ 7.95-7.92 (m, 2H), 7.56 (d, J= 8.1 Hz, 1H), 7.54-7.49 (m,
1H), 7.44-7.38 (m, 4H), 4.77 (q, J= 6.9 Hz, 1H), 1.56 (d, J= 6.9 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 199.8, 145.5, 136.2, 133.3, 129.2 (q, JCF= 32.5 Hz), 128.9,
128.8, 128.3, 126.1 (q, JCF= 3.7 Hz), 124.1 (q, JCF= 271.9 Hz), 47.6, 19.6. 19F NMR (377 MHz, CDCl3): δ -62.5
Analytical data matches previously reported characterisation. 44. 2-(3-(Dimethylamino)phenyl)-1-phenylpropan-1-one:
Pd loading 0.05 mol%. Yield 85%, 215 mg, green solid.
1H NMR (400 MHz, CDCl3): δ 7.98-7.95 (m, 2H), 7.48-7.43 (m, 1H), 7.39-7.34 (m, 1H),
7.16 (t, J= 7.9 Hz, 1H), 6.64 (d, J= 7.6 Hz, 1H), 6.61-6.55 (m, 2H), 4.61 (q, J= 6.8 Hz, 1H), 2.91 (s, 6H), 1.53 (d, J= 6.8 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 200.5, 151.0, 142.4, 136.7, 132.6, 129.6, 128.7, 128.4, 116.1,
111.5, 111.0, 48.5, 40.5, 19.5.
HRMS: Calculated for C17H19NO: 254.1445, Found: [M+H]+ = 254.1541
45. 2-(Benzo[d][1,3]dioxol-5-yl)-1-phenylethan-1-one:4
Pd loading 0.02 mol%. Yield 84%, 203 mg, yellow oil.
1H NMR (400 MHz, CDCl3): δ 8.02-7.99 (m, 2H), 7.59-7.54 (m, 1H), 7.49-7.43 (m, 2H), 6.78-6.69 (m, 3H), 5.93 (s, 2H), 4.20 (s, 2H). O N O CF3 O NMe2 O O O
13C NMR (100 MHz, CDCl3): δ 197.8, 148.0, 146.7, 136.7, 133.3, 128.8, 128.7, 128.2, 122.7,
110.0, 108.6, 101.1, 45.2.
Analytical data matches previously reported characterisation. 46. 2-(4-(Methylsulfonyl)phenyl)-1-phenylpropan-1-one:
Pd loading 0.05 mol%. Yield 70%, 203 mg, white solid.
1H NMR (400 MHz, CDCl3): δ 7.93 (d, J= 7.4 Hz, 2H), 7.87 (d, J= 8.3 Hz, 2H), 7.55-7.48
(m, 3H), 7.41 (t, J= 7.7 Hz, 2H), 4.81 (q, J= 6.9 Hz, 1H), 3.01 (s, 3H), 1.56 (d, J= 6.9 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 199.4, 147.7, 139.2, 136.0, 133.5, 129.0, 128.9, 128.8, 128.1,
47.5, 44.6, 19.5.
HRMS: Calculated for C16H16O3S: 306.1164, Found: [M+NH4]+ = 306.1161
47. 2-(4-Benzoylphenyl)-1-phenylpropan-1-one:8
Pd loading 0.05 mol%. Yield 81%, 225 mg, yellow solid.
1H NMR (400 MHz, CDCl3): δ 7.98-7.94 (m, 2H), 7.77-7.73 (m, 4H), 7.60-7.55 (m, 1H),
7.54-7.49 (m, 1H), 7.48-7.39 (m, 6H), 4.79 (q, J= 6.9 Hz, 1H), 1.58 (d, J= 6.9 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 199.8, 196.3, 137.7, 136.4, 133.2, 132.5, 131.0, 130.1, 128.9,
128.8, 128.4, 127.9, 47.9, 19.5.
Analytical data matches previously reported characterisation.
48. 1-(4-(Dimethylamino)phenyl)-2-(2,6-dimethylphenyl)ethan-1-one:
Pd loading 0.05%. Yield 78%, 208 mg, green solid.
1H NMR (400 MHz, CDCl3): δ 8.03-7.99 (m, 2H), 7.12-7.04 (m, 3H), 6.72-6.68 (m, 2H),
4.30 (s, 2H), 3.08 (s, 6H), 2.24 (s, 6H).
13C NMR (100 MHz, CDCl3): δ 194.8, 153.4, 137.0, 133.4, 130.2, 127.8, 126.5, 125.1, 110.6,
40.0, 38.8, 20.4.
HRMS: Calculated for C18H21NO: 268.1701, Found: [M+H]+ = 268.1695
O SO2Me
O
O
O
55. 6-Methoxy-2-phenyl-3,4-dihydronaphthalen-1(2H)-one:9
Pd loading 0.05%. Yield 93%, 235 mg, brown solid.
1H NMR (400 MHz, CDCl3): δ 8.08 (d, J= 8.7 Hz, 1H), 7.37-7.31 (m, 2H), 7.28-7.23 (m,
1H), 7.20-7.17 (m, 3H), 3.88 (s, 3H), 3.79-3.74 (m, 1H), 3.09-2.95 (m, 2H), 2.44-2.38 (m, 2H).
13C NMR (100 MHz, CDCl3): δ 197.1, 163.7, 146.7, 140.2, 130.4, 128.6, 128.5, 127.0, 126.7,
113.4, 112.7, 55.6, 54.2, 31.5, 29.1.
Analytical data matches previously reported characterisation.