Cu-Catalyzed Selective Oxygenation of Aryl C–H Bonds with O2 and MnO2 as Terminal Oxidants

Muhammad Siddique Ahmad; Qifeng Wang; Kamel Meguellati

doi:10.1055/a-1906-2916

Synlett, Table of Contents

Synlett 2025; 36(04): 412-420
DOI: 10.1055/a-1906-2916

letter

Cu-Catalyzed Selective Oxygenation of Aryl C–H Bonds with O₂ and MnO₂ as Terminal Oxidants

Muhammad Siddique Ahmad ∗

^aSchool of Pharmacy, Jinan University, 855 Xingye Avenue East, Guangzhou, 511436, P. R. of China

,

Qifeng Wang

^bCollege of Chemistry, Jilin University, 2699 Qianjin Street, Changchun, 130012, P. R. of China

,

Kamel Meguellati ∗

^aSchool of Pharmacy, Jinan University, 855 Xingye Avenue East, Guangzhou, 511436, P. R. of China

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Abstract

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Abstract

Herein, we present efficient methods for the selective copper-catalyzed oxidation of aromatic C–H bonds in the presence of O₂ and/or MnO₂. Various 2-arylpyridines and 2-arylpyrimidines are used for the controlled synthesis of mono- and diacetoxylative products in moderate to good yields (29–99%) in the presence of CuO(nano) (20 mol%), O₂ and HOAc/Ac₂O as an acetoxy source and solvent. The mono selective hydroxylation of C–H bonds is also achieved with Cu(OAc)₂ as the catalyst. Mechanistically, a trivalent copper intermediate might be involved in the catalytic cycle.

Key words

copper - C–H bond activation - hydroxylation - acetoxylation - 2-arylpyridines

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References

References and Notes

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3-Methyl-2-(4-(trifluoromethyl)phenyl)pyridine (1m)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. After cooling, the mixture was poured into brine (2 × 30 mL) and extracted with ethyl acetate (4 × 30 mL). The combined organic layer was evaporated in vacuo and the product was isolated by short column chromatography over silica gel.Yield: 24%; colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.53 (d, J = 4.8 Hz, 1 H), 7.71 (d, J = 8.4 Hz, 2 H), 7.64 (d, J = 8.4 Hz, 2 H), 7.61 (d, J = 7.6 Hz, 1 H), 7.22 (dd, J = 4.8, 7.6 Hz, 1 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.1, 147.2, 144.0, 138.7, 130.9, 129.8, 129.4, 125.5, 125.1, 125.0, 122.7, 29.7, 19.9. IR (KBr): 1674, 1405, 1384, 1325, 850,792, 515 cm^–1. MS (EI): m/z = 237.1 [M]⁺, 236.1 [M – 1]⁺, 218.1, 216.1, 167.1, 166.1. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₀F₃N: 237.0765; found: 237.0762.
18 3-Methyl-2-(3-(trifluoromethyl)phenyl)pyridine (1n)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 54%; yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.55 (d, J = 4.0 Hz, 1 H), 7.81 (s, 1 H), 7.73 (d, J = 7.6 Hz, 1 H), 7.66 (d, J = 8.0 Hz, 1 H), 7.60 (d, J = 8.0 Hz, 1 H), 7.57 (t, J = 7.6 Hz, 1 H), 7.23 (dd, J = 4.8, 8.0 Hz, 1 H), 2.36 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 147.2, 141.3, 138.7, 132.3, 131.0, 130.9, 128.6, 125.9, 125.8, 124.7, 124.6, 122.7, 19.9. IR (KBr): 2931, 1584, 1568, 1456, 1418, 1335, 809, 790, 703, 658 cm^–1. MS (EI): m/z = 237.1 [M]⁺, 236.1 [M – 1]⁺, 216.1, 167.1, 166.1. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₀F₃N: 237.0765; found: 237.0760.
19 2-(4-Fluorophenyl)-3-methylpyridine (1p)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 52%; yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 4.8 Hz, 1 H), 7.58 (d, J = 7.6 Hz, 1 H), 7.52–7.47 (m, 2 H), 7.17 (dd, J = 4.8, 7.6 Hz, 1 H), 7.15–7.10 (m, 2 H), 2.34 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 163.6, 161.2, 157.1, 146.8, 142.6, 142.5, 138.5, 130.7, 129.5, 129.5, 124.6, 122.3, 116.0, 115.8, 114.8, 114.6. IR (KBr): 2962, 2918, 1637, 1384, 1260, 800, 609, 513 cm^–1. MS (EI): m/z = 187.1 [M]⁺, 186.1 [M – 1]⁺, 184.1, 166.1, 159.1, 133.0, 112.0. HRMS (EI): m/z [M]⁺ calcd for C₁₂H₁₀FN: 187.0797; found: 187.0799.
20 2-(4-(tert-Butyl)phenyl)-3-methylpyridine (1q)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 80%; colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 4.8 Hz, 1 H), 7.56 (d, J = 7.6 Hz, 1 H), 7.46 (s, 4 H), 7.15 (dd, J = 4.8, 7.6 Hz, 1 H), 2.38 (s, 3 H), 1.34 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.6, 150.8, 146.9, 138.4, 137.7, 130.7, 128.6, 125.0, 121.8, 34.6, 31.3, 20.1. IR (KBr): 2962, 1613, 1584, 1573, 1468, 1446, 1424, 842, 789, 775, 657, 590 cm^–1. MS (EI): m/z = 225.2 [M]⁺, 224.2 [M – 1]⁺, 210.1, 195.1, 181.1, 168.1. HRMS (EI): m/z [M]⁺ calcd for C₁₆H₁₉N: 225.1517; found: 225.1515.
21 2-(3-Methoxyphenyl)-3-methylpyridine (1r)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH /H₂O(v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 63%; yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 4.8 Hz, 1 H), 7.57 (d, J = 7.6 Hz, 1 H), 7.35 (t, J = 8.0 Hz, 1 H), 7.17 (dd, J = 4.8, 7.6 Hz, 1 H), 7.08 (d, J = 7.6 Hz, 1 H), 7.06 (t, J = 2.4 Hz, 1 H), 6.94 (dd, J = 2.8, 8.4 Hz, 1 H), 3.85 (s, 3 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 159.7, 158.8, 147.1, 142.2, 138.7, 131.1, 129.2, 122.4, 121.6, 114.5, 114.1, 55.5, 20.3. IR (KBr): 2936, 1582, 1488, 1459, 1427, 879, 788, 766, 701 cm^–1. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₃NO: 199.0997; found: 200.1082.
22 3-Methyl-2-(m-tolyl)pyridine (1s)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 72%; colorless oil. ¹H NMR (400 MHz, CDCl₃): δ = 2.35 (s, 3 H), 2.41 (s, 3 H), 7.17 (dd, J = 4.8, 7.6 Hz, 1 H), 7.20 (d, J = 6.8 Hz, 1 H), 7.31 (dd, J = 7.2, 10.8 Hz, 2 H), 7.35 (s, 1 H), 7.57 (d, J = 7.6 Hz, 1 H), 8.52 (d, J = 4.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.8, 146.8, 140.5, 138.3, 137.7, 130.7, 129.5, 128.5, 127.8, 125.8, 121.9, 21.4, 20.0. IR (KBr): 2926, 1624, 1577, 1188 cm^–1. MS (EI): m/z =183 [M]⁺, 182, 180, 167, 166, 51, 39. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₃N: 183.1044; found: 183.1048.
23 2-(4-(tert-Butyl)phenyl)pyrimidine (1aa)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 78%; white solid; mp 46–48 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.79 (d, J = 4.0 Hz, 2 H), 8.38–8.34 (m, 2 H), 7.53–7.50 (m, 2 H), 7.15 (t, J = 4.8 Hz, 1 H), 1.36 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.7, 157.2, 157.1, 154.1, 134.8, 127.9, 125.5, 118.7, 34.8, 31.2. IR (KBr): 2969, 1606, 1568, 1551, 1417, 808, 800, 575, 482 cm^–1. MS (EI): m/z =212.1 [M]⁺, 211.1 [M – 1]⁺, 197.1, 169.1. HRMS (EI): m/z [M]⁺ calcd for C₁₄H₁₆N₂: 212.1313; found: 212.1315.
24 2-(3-Fluorophenyl)-3-methylpyridine (1ad)A mixture of the corresponding heteroaryl bromide (10 mmol, 1 equiv), phenylboronic acid (15 mmol, 1.5 equiv), Pd(OAc)₂ (1.5 mol%), K₃PO₄·7H₂O (20 mmol, 2 equiv) and 50% isopropanol (80 mL, i-PrOH/H₂O (v/v = 1:1)) was stirred at 80 °C for 10 h under an oxygen balloon. See Ref. 18 for the work-up procedure.Yield: 44%; yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.51 (d, J = 4.8 Hz, 1 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.41 (dt, J = 6.0, 8.0 Hz, 1 H), 7.30 (dt, J = 1.2, 8.0 Hz, 1 H), 7.26–7.22 (m, 1 H), 7.19 (dd, J = 4.8, 7.6 Hz, 1 H), 7.09 (td, J = 2.8, 8.8 Hz, 1 H), 2.35 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 163.8, 161.3, 157.3, 147.0, 138.6, 130.8, 129.7, 129.6, 124.7, 122.5, 116.1, 116.0, 114.9, 114.7, 19.9. IR (KBr): 2975, 1613, 1583, 1567, 1486, 1455, 1433, 891, 787, 766 cm^–1. HRMS (EI): m/z [M]⁺ calcd for C₁₂H₁₀FN: 187.0797; found: 188.0900.
25 4-Methyl-2-(pyridin-2-yl)phenol (2b)In a sealed tube, a solution of substrate 1b (62 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (1:1, 1.33 mL) was stirred at 150 °C for 60 h. For work up, we used ethylacetate and water for extraction add brine solution in extraction and evaporated. Finally, mixture is purified with column chromatography 1:5 (PE:EA).Yield: 59%; white solid; mp 66–68 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.14 (s, 1 H), 8.50–8.51 (m, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 7.80–7.84 (m, 1 H), 7.59 (s, 1 H), 7.23 (ddd, J = 1.2, 4.8, 7.6 Hz, 1 H), 7.12 (dd, J = 2.0, 8.4 Hz, 1 H), 6.94 (d, J = 8.4 Hz, 1 H), 2.34 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.9, 157.7, 145.9, 137.6, 132.4, 132.3, 127.6, 126.2, 121.3, 118.9, 118.3, 20.7. IR (KBr): 3434, 2921, 1595, 1493, 1241, 818 cm^–1. MS (EI): m/z = 187, 186, 185 [M]⁺, 184, 156, 117, 78, 51, 39. HRMS (EI): m/z [M]⁺ calcd for C₁₂H₁₁NO: 185.0835; found: 185.0841.
26 5-(tert-Butyl)-2-(pyridin-2-yl)phenol (2d)In a sealed tube, a solution of substrate 1d (62 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 69%; faint yellow solid; mp 53–55 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.30 (s, 1 H), 8.47–8.48 (m, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 7.76–7.81 (m, 1 H), 7.72 (d, J = 8.4 Hz, 1 H), 7.17–7.20 (m, 1 H), 7.06 (d, J = 2.0 Hz, 1 H), 6.93–6.96 (m, 1.33, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 159.6, 157.8, 155.3, 145.8, 137.6, 125.6, 121.0, 118.7, 116.1, 115.4, 34.5, 31.3. IR (KBr): 3435, 2953, 1615, 1597, 1579, 1555, 1471, 1417, 1385, 1357, 1281, 1256 cm^–1. MS (EI): m/z = 229, 228, 227 [M]⁺, 226, 213, 212, 210, 197, 185, 184, 104, 91, 78, 51, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₅H₁₇NO: 227.1307; found: 227.1310.
27 5-Fluoro-2-(pyridin-2-yl)phenol (2f)In a sealed tube, a solution of substrate 1f (53 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 59%; white solid; mp 112–113 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.82 (s, 1 H), 8.48 (d, J = 5.2 Hz, 1 H), 7.83–7.82 (m, 1 H), 7.75 (dd, J = 8.8, 6.4 Hz, 1 H), 7.26–7.22 (m, 1 H), 6.72 (dd, J = 10.4, 2.4 Hz, 1 H), 6.62 (dt, J = 8.0, 2.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.6 (d, J _C–F = 246.1 Hz), 157.2, 145.6, 137.9, 127.5, 121.4, 118.8, 115.3, 109.8, 106.3 (d, J _C–F = 22.2 Hz), 105.2 (d, J _C–F = 23.1 Hz). IR (KBr): 3468, 2520, 1602, 1561, 1517, 1473, 1415, 1399, 1279, 1244, 1154, 1118 cm^–1. MS (EI): m/z = 191, 190, 189 [M]⁺, 188, 160, 159, 135, 133, 78, 51. HRMS (EI): m/z [M]⁺ calcd for C₁₁H₈FNO: 189.0588; found: 189.0590.
28 5-Chloro-2-(pyridin-2-yl)phenol (2g)In a sealed tube, a solution of substrate 1g (55 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 52%; white solid; mp 83–83 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.8 (s, 1 H), 8.48 (dd, J = 3.6, 1.2 Hz, 1 H), 7.86–7.83 (m, 1 H), 7.69 (d, J = 4.4 Hz, 2 H), 7.27–7.25 (m, 1 H), 7.03 (t, J = 2.0 Hz, 1 H), 6.78 (dd, J = 8.4, 2.4 Hz, 1 H). ¹³C NMR (100 MHz,CDCl₃): δ = 160.8, 156.9, 145.8, 137.9, 136.7, 126.9, 121.8, 119.1, 119.0, 118.6, 117.3. IR (KBr) 3450, 2955, 2925, 1594, 1581, 1557, 1501, 1463, 1414, 1266, 1220, 1099, 1084 cm^–1. MS (EI): m/z = 208, 207, 205 [M]⁺, 204, 179, 177, 153, 151, 142, 117, 78, 51. HRMS (EI): m/z [M]⁺ calcd for C₁₁H₈ClNO: 205.0296; found: 205.0294.
29 4-Methoxy-2-(pyridin-2-yl)phenol (2h)In a sealed tube, a solution of substrate 1h (57 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 51%; faint yellow solid, mp 92 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.82 (s, 1 H), 8.53–8.51 (m, 1 H), 7.88–7.81 (m, 1 H), 7.31 (d, J = 2.8 Hz, 1 H), 7.26–7.23 (m, 1 H), 6.97 (d, J = 8.8 Hz, 1 H), 6.94 (d, J = 2.8 Hz, 1 H), 3.83 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 157.5, 154.0, 152.1, 146.0, 137.7, 121.6, 119.2, 119.1, 118.8, 117.8, 110.9, 56.0. IR (KBr): 3459, 2924, 1631, 1595, 1564, 1419, 1385, 1211, 1041 cm^–1. MS (EI): m/z = 203, 202, 201 [M]⁺, 187, 186, 159, 158, 141, 130, 128, 104, 89, 78, 51, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₂H₁₁NO₂: 201.0788; found: 201.0790.
30 2-(Pyridin-2-yl)-5-(trifluoromethyl)phenol (2i)In a sealed tube, a solution of substrate 1i (63 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 61%; white solid; mp 74–75 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.65 (s, 1 H), 8.7 (d, J = 4.4 Hz, 1 H), 7.97 (d, J = 8.4 Hz, 1 H), 7.91 (dt, J = 2.0, 7.6 Hz, 2 H), 7.33–7.36 (m, 1 H), 7.28 (s, 1 H), 7.14 (d, J = 8.4 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.0, 156.6, 146.0, 138.1, 133.1, 126.6, 125.5 (q, J _C–F = 248.3 Hz), 122.5, 121.5, 119.5, 115.8, 115.0. IR (KBr): 3435, 2923, 1583, 1106 cm^–1. MS (EI): m/z = 241, 240, 239 [M]⁺, 238, 220, 211, 191, 141, 117, 78, 51. HRMS (EI): m/z [M]⁺ calcd for C₁₂H₈F₃NO: 239.0559; found: 239.0558.
31 Methyl 3-Hydroxy-4-(pyridin-2-yl)benzoate (2j)In a sealed tube, a solution of substrate 1j (56 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 25%; faint yellow solid; mp 111–115 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.43 (s, 1 H), 8.56 (d, J = 4.8 Hz, 1 H), 7.98 (d, J = 8.4 Hz, 1 H), 7.91 (dd, J = 1.6, 7.6 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 7.69 (d, J = 1.6 Hz, 1 H), 7.57 (dd, J = 1.6, 8.4 Hz, 1 H), 7.33 (ddd, J = 0.8, 4.8, 7.2 Hz, 1 H), 3.93 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.3, 159.7, 156.8, 146.1, 138.0, 132.5, 126.0, 122.4, 119.9, 119.9, 119.8, 119.5, 52.2. IR (KBr): 1734, 1597, 1477, 1137 cm^–1. MS (EI): m/z = 231, 230, 229 [M]⁺, 228, 198, 171, 142, 78, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₁NO₃: 229.0740; found: 229.0739.
32 5-Methyl-2-(pyridin-2-yl)phenyl Acetate (3b)In a sealed tube, a solution of substrate 1b (53 mg, 0.4 mmol) and CuO(nano) (3.2 mg, 0.04 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 130 °C for 48 h under an oxygen atmosphere. For workup, we used ethylacetate and water for extraction add brine solution in extraction and evaporated. Finally, mixture is purified with column chromatography 1:5 (PE:EA).Yield: 44%; faint yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.68 (d, J = 4.8 Hz, 1 H), 7.71 (dt, J = 8.0, 2.0 Hz, 1 H), 7.59 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.24–7.20 (m, 1 H), 7.16 (d, J = 7.6 Hz, 1 H), 6.98 (s, 1 H), 2.40 (s, 3 H), 2.18 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 169.6, 155.7, 149.4, 147.8, 140.2, 136.2, 130.5, 130.1, 127.2, 123.6, 123.4, 121.9, 21.1, 20.9. IR (KBr): 3452, 3024, 2922, 1746, 1618, 1596, 1559, 1474, 1416, 1384, 1278, 1242, 1226, 1159 cm^–1. MS (EI): m/z = 227 [M]⁺, 201, 186, 185, 184, 157, 156, 154, 90, 78, 51, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₄H₁₃NO₂: 227.0944; found: 227.0946.
33 Methyl 3-Hydroxy-4-(pyridin-2-yl)benzoate (2j)In a sealed tube, a solution of substrate 1j (56 mg, 0.4 mmol), H₂O (72 mg, 4 mmol), Cu(OAc)₂ (14.4 mg, 0.08 mmol), 30% H₂O₂ (113 mg, 1 mmol) and MnO₂ (20.8 mg, 0.24 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 150 °C for 60 h. See Ref. 26 for the work-up procedure.Yield: 25%; faint yellow solid; mp 111–115 °C. ¹H NMR (400 MHz, CDCl₃): δ = 14.43 (s, 1 H), 8.56 (d, J = 4.8 Hz, 1 H), 7.98 (d, J = 8.4 Hz, 1 H), 7.91 (dd, J = 1.6, 7.6 Hz, 1 H), 7.87 (d, J = 8.4 Hz, 1 H), 7.69 (d, J = 1.6 Hz, 1 H), 7.57 (dd, J = 1.6, 8.4 Hz, 1 H), 7.33 (ddd, J = 0.8, 4.8, 7.2 Hz, 1 H), 3.93 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.3, 159.7, 156.8, 146.1, 138.0, 132.5, 126.0, 122.4, 119.9, 119.9, 119.8, 119.5, 52.2. IR (KBr): 1734, 1597, 1477, 1137 cm^–1. MS (EI): m/z = 231, 230, 229 [M]⁺, 228, 198, 171, 142, 78, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₃H₁₁NO₃: 229.0740; found: 229.0739.
34 5-(tert-Butyl)-2-(pyridin-2-yl)phenyl Acetate (3c)In a sealed tube, a solution of substrate 1c (70 mg, 0.4 mmol) and CuO(nano) (3.2 mg, 0.04 mmol) in HOAc/Ac₂O (v/v = 1:1, 1.33 mL) was stirred at 130 °C for 48 h under an oxygen atmosphere. See Ref. 33 for the work-up procedure.Yield: 38%; faint yellow oil. ¹H NMR (400 MHz, CDCl₃): δ = 8.68 (d, J = 4.0 Hz, 1 H), 7.72 (dt, J = 7.6, 1.6 Hz, 1 H), 7.63 (d, J = 8.0 Hz, 1 H), 7.52 (d, J = 8.0 Hz, 1 H), 7.38 (dd, J =8.0, 1.2 Hz, 1 H), 7.24–7.20 (m, 1 H), 7.14 (d, J = 1.2 Hz, 1 H), 2.18 (s, 3 H), 1.35 (s, 9 H). ¹³C NMR (100MHz,CDCl₃): δ = 169.5, 155.7, 153.5, 149.3, 147.7, 136.3, 130.2, 129.9, 123.5, 123.4, 122.0, 120.1, 34.7, 31.1, 21.0. IR (KBr): 3437, 2963, 2868, 1746, 1618, 1596, 1579, 1472, 1417, 1382, 1284, 1227, 1203 cm^–1. MS (EI): m/z = 229 [M]⁺, 228, 227, 212, 185, 184, 167, 117, 78, 51, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₇H₁₉NO₂: 269.1419; found: 269.1416.
35 5-(tert-Butyl)-2-(pyridin-2-yl)-1,3-phenylene Diacetate (4c)In a sealed tube, a solution of substrate 1c (62 mg, 0.4 mmol) and CuO(nano) (3.2 mg, 0.04 mmol) in HOAc/Ac₂O (v/v = 1;1, 1.33 mL) was stirred at 130 °C for 48 h under an oxygen atmosphere. See Ref. 32 for the work-up procedure.Yield: 61%; faint yellow solid; mp 125–128 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.67 (d, J = 4.8 Hz, 1 H), 7.71 (dt, J = 8.0, 2.0 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 1 H), 7.25–7.22 (m, 1 H), 7.10 (s, 2 H), 2.02 (s, 6 H), 1.34 (s, 9 H). ¹³C NMR (100 MHz, CDCl₃): δ = 168.9, 153.5, 152.5, 149.3, 148.6, 135.8, 125.0, 124.5, 122.2, 117.7, 34.9, 30.9, 20.6, IR (KBr): 2965, 1760, 1628, 1586, 1462, 1429, 1414, 1370, 1207, 1054 cm^–1. MS (EI): m/z = 327 [M]⁺ (M⁺), 312, 286, 285, 244, 243, 228, 201, 130, 120, 92, 78, 43. HRMS (EI): m/z [M]⁺ calcd for C₁₉H₂₁NO₄: 327.1468; found: 327.1471.

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