First Example of Quinoxaline-Directed C-H Activation: A Novel Method for Acetoxylation of Arenes

Abstract

2-Aryl- and 2,3-diarylquinoxalines undergo smooth acetoxylation in the presence of 5 mol% Pd(OAc)₂ and a stoichiometric amount of PhI(OAc)₂ via C-H activation to produce the corresponding acetoxy-susbstituted quinoxaline derivatives in excellent yields with high regioselectivity.

Key words

hypervalent iodine reagent - aryl quinoxalines - acetoxylation - C-H activation

References and Notes

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11

Typical Experimental Procedure
A mixture of 2,3-diphenylquinoxaline (100 mg, 0.35 mmol), PhI(OAc)₂ (250 mg, 0.78 mmol), and Pd(OAc)₂ (4 mg, 0.05 mmol) in DCE (5 mL) was stirred at r.t. for 10 min, then the resulting mixture was heated to 90 ˚C for 12 h. After completion of reaction as indicated by TLC, the reaction mixture was filtered, diluted with H₂O and extracted with CH₂Cl₂ (2 × 15 mL). The combined organic layers were dried over anhyd Na₂SO₄, concentrated in vacuo, and purified by column chromatography on silica gel (Merck, 60-120 mesh, EtOAc-hexane, 0.5:9.5) to afford pure bisacetoxy derivative.
Compound 3c: yellow solid, mp 143-144 ˚C. IR (KBr):
ν_max = 3027, 2923, 2854, 1765, 1620, 1458, 1370, 1190, 1116, 1031, 909, 758 cm^-¹. ^¹H NMR (300 MHz, CDCl₃):
δ = 2.10 (s, 3 H), 2.48 (s, 3 H), 7.01-7.07 (m, 2 H), 7.24-7.30 (m, 2 H), 7.79 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.3, 20.8, 123.0, 125.5, 128.8, 129.8, 131.3, 131.4, 139.8, 140.0, 148.2, 149.7, 168.9. MS (EI): m/z = 449 [M + Na]. HRMS: m/z calcd for C₂₆H₂₂N₂O₄Na: 449.1477; found: 449.1475.
Compound 3e: yellow solid, mp 161-162 ˚C. IR (KBr):
ν_max = 3029, 2922, 2852, 1769, 1715,1442, 1374, 1310, 1278, 1254, 1181, 1112, 1054, 1027, 907, 807 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.09 (s, 3 H), 2.10 (s, 3 H), 4.03 (s, 3 H), 7.17 (m, 4 H), 7.41 (m, 4 H), 8.18 (s, 1 H), 8.39 (dd, 1 H, J = 1.8, 8.6 Hz), 8.85 (d, 1 H, J = 1.7 Hz). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.8, 20.9, 52.6, 123.2, 125.6, 129.4, 129.8, 130.3, 130.6, 130.7, 131.4, 131.6, 131.7, 140.1, 142.7, 148.3, 151.9, 152.7, 166.1, 168.7, 168.8. MS (EI): m/z = 479 [M + Na]. HRMS: m/z calcd for C₂₆H₂₀N₂O₆Na: 479.1219; found: 479.1202.
Compound 3j: pale yellow solid, mp 103-104 ˚C. IR (neat): ν_max = 3020, 2923, 2852, 1764, 1646, 1544, 1488, 1448, 1369, 1312, 1187, 1108, 1034, 1010, 958, 912, 867, 764 cm^-¹. ^¹H NMR (300 MHz, CDCl₃): δ = 2.23 (s, 3 H), 7.21 (s, 1 H), 7.39-7.57 (m, 2 H), 7.74-7.80 (m, 2 H), 7.91 (dd, 2 H, J = 1.3, 6.2 Hz), 8.21 (m, 2 H), 9.10 (s, 1 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 20.9, 123.5, 128.1, 129.1, 129.4 129.5, 129.9, 130.2, 130.3, 130.9, 131.1, 141.1, 148.5, 150.8, 169.3. MS (EI): m/z = 287 [M + Na]. HRMS: m/z calcd for C₁₆H₁₂N₂O₂Na: 287.0796; found: 287.0784.