English

• 1.   Introduction

  Carbon-centered radicals play important roles in chemical transformations and serve as versatile synthetic intermediates.^[1] Therefore, methods for chemical bond formation based on carbon-centered radicals have gained much attention from the scientific community. Carbon-centered radicals relay functionalization, usually proceeding through two or more consecutive steps, and are synthetically attractive as they provide easy access to highly functionalized, often polycyclic, skeletons in a step-economic manner.^[2] Structurally diverse polycyclic benzimidazole[2, 1-a]isoquinolines are important synthetic intermediates and key structural motifs in biologically active molecules.^[3] Numerous methods have thus been reported toward these carbocyclic frameworks, however, many of these are heavily dependent on multi-step condensation reactions with pre-functionalized starting materials, with limited functional group tolerability and low overall yields.^[4] Therefore, investigating more general methods, especially one-pot strategies, to access these frameworks with readily available starting materials is highly desirable. Radical-based carbocyclization reactions, initiated by intermolecular addition of carbon-centered radicals to π systems, is undoubtedly good method for the rapid and convenient construction of these frameworks with high atom and step economy.^[5]

  In 2018, an ingenious Cp*Rh(III)-catalyzed [4+2] annulation for the synthesis of benzimidazole[2, 1-a]iso- quinolines with 2-arylimidazoles and a-diazoketoesters was realized by Song et al. (Scheme 1a).^[6] Later, Chen and Yu et al.^[7] reported a silver-catalyzed decarboxylative carbon-centered radical addition/cyclization and visible- light-induced radical cyclization to access benzimidazole- [2, 1-a]isoquinolines (Scheme 1b). However, stoichiometric acid/base additives, environmentally unfriendly halohydrocarbons and inconvenient inert gas operating requirements, severely limit the synthetic application of these protocols. The “magic methyl effect” has had a profound impact on biological activities, pharmacokinetic profiles, and physical properties, thus, investigation of methods for the direct introduction of methyl groups has attracted much attention from chemists.^[8] Along with the widely used alkyl-metallic reagents, alkyl boronates and redox-active esters, the use of peroxides as alternative methylation reagents has also achieved success in many studies. The reaction of di-tert-butyl peroxide (DTBP) with benzaldehyde for the synthesis of diphenylethylene glycol dibenzoate was reported in 1948.^[9] Later, the use of dicumyl peroxide (DCP), ^[10] tert-butyl peroxybenzoate (TBPB), ^[11] DTBP^[12] and tert-butyl hydroperoxide (TBHP)^[13] as methylation reagents was widely reported. With our continued interest in the derivatization of nitrogen-containing heterocycles^[14] and radical chemistry, ^[15] we thus wondered whether alkyl peroxides could initiate the intermolecular addition of carbon-centered radicals to π systems, to achieve a radical relay carbocyclization, which would offer an unprecedented approach to polycyclic benzimidazole[2, 1-a]isoquino- lines in a straightforward manner (Scheme 1c).

  图式 1

  

  图式 1.  Synthesis of benzimidazo-isoquinoline frameworks

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  2.   Results and discussion

  We initiated our studies by screening the reaction conditions with N-methacryloyl-2-phenylbenzoimidazole (1a) as substrate and various peroxides as methylation reagents (Table 1). The experiments revealed that DCP showed low reactivity, while TBHP and DTBP failed to afford the desired product 2a (Entries 1~3). It was found that TBPB was a good choice, and 2a was obtained in 51% yield (Entry 4). Therefore, the reaction was then carried out in different solvents, including DMSO, CH₃NO₂, THF, DCE and EtOAc, to optimize the yield. The most favorable solvent was found to be CH₃NO₂, leading to an evident improvement in the yield of 2a (63%) (Entries 5~9). In addition, parallel reactions with different additives such as FeCl₂, FeCl₃, Fe(OTf)₃ and ferrocene (Cp₂Fe) were carried out, and Cp₂Fe was found to be the best promoter, affording 2a in up to 84% yield (Entries 10~13). Decreasing the loading of Cp₂Fe from 20% to 10% had no obvious effect on yield of 2a, however, the yield was slightly lower with 5% Cp₂Fe added (Entries 14~16). Further examination on the impact of reaction time and temperature showed that 1 h was enough to achieve the formation of 2a with a high yield, while a decrease in the yield was observed when the reaction temperature was decreased from 120 ℃ to 90 ℃ and 60 ℃ (Entries 17~19).

  表 1

  

  表 1  Survey of the reaction conditions^{a, b}

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  Entry	Oxidant	Catalyst (mol%)	Solvent	Yield/%
  1	DCP	None	CH3CN	23
  2	TBHP	None	CH3CN	Trace
  3	DTBP	None	CH3CN	0
  4	TBPB	None	CH3CN	51
  5	TBPB	None	DMSO	23
  6	TBPB	None	CH3NO2	63
  7	TBPB	None	THF	0
  8	TBPB	None	DCE	39
  9	TBPB	None	EtOAc	0
  10	TBPB	FeCl2 (20)	CH3NO2	45
  11	TBPB	FeCl3 (20)	CH3NO2	26
  12	TBPB	Fe(OTf)3 (20)	CH3NO2	Trace
  13	TBPB	Cp2Fe (20)	CH3NO2	84
  14	TBPB	Cp2Fe (15)	CH3NO2	82
  15	TBPB	Cp2Fe (10)	CH3NO2	83
  16	TBPB	Cp2Fe (5)	CH3NO2	74
  17	TBPB	Cp2Fe (10)	CH3NO2	80c
  18	TBPB	Cp2Fe (10)	CH3NO2	45d
  19	TBPB	Cp2Fe (10)	CH3NO2	11e
  a Reactions were carried out with 1a (0.3 mmol), peroxides (2.0 equiv.), catalyst (5~20 mol%) and solvent (2 mL) refluxed at 120 ℃ for 1 h. b Yield of the isolated product. c Reaction performed at 120 ℃ for 6 h. d Reaction performed at 90 ℃ for 6 h. e Reaction performed at 60 ℃ for 6 h.

  With the optimal reaction conditions, the substrate scope was explored as shown in Table 2. A wide range of functional groups, including electron-withdrawing and electron-donating groups at the ortho-, meta- and para-positions of the phenyl rings, were compatible with the reaction conditions, giving the corresponding products 2b~2n in moderate to excellent yields (53%~91%). In this reaction, halo-substituents (Cl, Br and I) on the phenyl ring, provide a handle for further transformations. Strongly electron-withdrawing groups (CF₃, COOMe, SO₂Me), which are negative to the radical carbocyclization, underwent smoothly the reaction to give 2l~2n in good yields. Notably, in place of a benzene ring, 2-thiophen-substituted substrate 1o, which is usually sensitive in oxidizing radical coupling systems, was well tolerated, and the corresponding product 2o was obtained in reasonable yield (63%). In addition, 2-naphthalen-substituted 1H-benzo[d]imidazole 1p and polysubstituted substrates 1q and 1r, were also smoothly converted to the corresponding products 2p, 2q and 2r in moderate to good yields (55%~82%).

  表 2

  

  表 2  Substrate scope^{a, b}

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  With the developed strategy in hand, benzoyl peroxide (BPO), another phenyl radical precursor, ^[16] was reacted with substrates 1, with the hope of constructing some other structurally diverse benzimidazole[2, 1-a]isoquinolines. After screening of reaction conditions, contrary to the previous system, it was found that Cp₂Fe did not require in this reaction. The scope of substrates 1 was briefly tested and the results are listed in Table 3. Substrates bearing electron-neutral (H) and electron-donating (Me and OMe) groups on the phenyl rings proceeded smoothly under the optimal conditions. The desired products 3a~3e were obtained in moderate to good yields (60%~79%). Obvious electronic effects were observed with substrates bearing electron-withdrawing groups (F, Cl, Br and CN) on the phenyl rings, affording the corresponding products 3f~3j in relatively low yields (30%~53%).

  表 3

  

  表 3  Substrate scope^{a, b}

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  Several control experiments were conducted to gain insights into the reaction mechanism. When the model reaction was treated with radical scavenger 2, 2, 6, 6-tetramethyl- piperidine-1-oxyl (TEMPO, 2 equiv), the yield of 2a decreased to 13% (Eq. 1). When 2, 6-di-tert-butyl-4-methyl- phenol (BHT, 2 equiv.) and 1, 1-diphenylethylene (2 equiv) were added under standard conditions, the reactions were totally suppressed, and the adducts 4 and 5 were detected via GC-MS analysis (Eqs. 3, 4). The above experiments supported a radical relay carbocyclization pathway. With the present findings and previous reports, ^[17] a possible radical relay carbocyclization mechanism is proposed in Scheme 2.

  图式 2

  

  图式 2.  Plausible catalytic cycle

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  (1)

  (2)

  (3)

  The reaction begins with the O—O bond cleavage of peroxides, providing O-centered radical species A. Further splitting of A by loss of one equivalent of acetone or carbon dioxide gives the free methyl or phenyl radical species B. In the presence of Fe(II), the generation of the tert- butoxy radical may be accelerated by a single electron transfer (SET) process, along with release the Fe(III) species. Then, the addition of radical species B to N-metha- cryloyl-2-phenyl-benzoimidazoles (1) provides another radical intermediate C, which undergoes an intramolecular relay cyclization to give the radical intermediate D. Subsequent reaction of intermediate D with the other O-cen- tered radical species A or the Fe(III) species generates a cationic intermediate E, then loss of a proton from E eventually affords the desired products 2 and 3.

  3.   Conclusions

  In summary, we have developed a simple and efficient peroxide-induced radical relay carbocyclization reaction from easily available N-methacryloyl-2-phenylbenzoimi- dazoles to assemble a series of structurally diverse and privileged polycyclic benzimidazo[2, 1-a]isoquinoline-6- (5H)-ones in a straightforward manner. Furthermore, this reaction features simple reaction conditions, broad substrate scope, good functional group tolerance and easy- handling. This mild radical relay carbocyclization strategy has inspired an interest in the synthesis of other polycyclic compounds, and related investigations are currently underway in our laboratory.

  4.   Experimental section

  4.1   Instruments and reagents

  All reagents were purchased from commercial sources and used without further purification. ¹H NMR and ¹³C NMR spectra were recorded on a Bruker Ascend™ 400 spectrometer in deuterated solvents containing TMS as an internal reference standard. High-resolution mass spectrometry (HRMS) analyses were conducted on a Waters LCT Premier/XE. Melting points were measured on a melting point apparatus equipped with a thermometer and were uncorrected. All the reactions were monitored by thin-layer chromatography (TLC) using GF254 silica gel- coated TLC plates. Purification by flash column chromatography was performed over SiO₂ (silica gel 200~300 mesh).

  4.2   General procedure for the synthesis of 2

  2-Methyl-1-(2-phenyl-1H-benzo[d]imidazol-1-yl)prop-2- en-1-one (1a) (78.7 mg, 0.3 mmol), ferrocene (5.6 mg, 10 mol%) and TBPB (114 μL, 2.0 equiv.) were mixed in 2 mL of CH₃NO₂, and then the mixture was refluxed at 120 ℃ in oil bath for 1 h. After completion of the reaction, the mixture was quenched by NaHCO₃ (sat. aq. 15 mL) and extracted with CH₂Cl₂ (5 mL×3). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography with petroleum ether/ethyl acetate (V:V＝10:1) as eluent to give 5- ethyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]isoquinolin-6(5H)- one (2a) (83% yield, 68.8 mg). White solid, m.p. 57~58 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.48 (d, J＝8.0 Hz, 1H), 8.41~8.33 (m, 1H), 7.87~7.77 (m, 1H), 7.62~7.54 (m, 1H), 7.53~7.38 (m, 4H), 2.51~2.38 (m, 1H), 2.09~1.96 (m, 1H), 1.73 (s, 3H), 0.58 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.49, 150.09, 144.14, 141.69, 132.00, 131.39, 127.79, 126.19, 125.98, 125.93, 125.65, 123.33, 119.87, 115.80, 50.18, 36.51, 28.48, 9.70. HRMS (ESI) calcd for C₁₈H₁₇N₂O [M+H]⁺ 277.1335, found 277.1339.

  5-Ethyl-1, 5-dimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoquino-lin-6(5H)-one (2b): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝20:1) as eluent to give 2b (69% yield, 60 mg). m.p. 94~95 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.44~8.37 (m, 1H), 7.88~7.81 (m, 1H), 7.48~7.38 (m, 3H), 7.38~7.28 (m, 2H), 3.06 (s, 3H), 2.50~2.36 (m, 1H), 2.07~1.94 (m, 1H), 1.73 (s, 3H), 0.58 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.64, 150.28, 144.32, 142.79, 139.76, 131.05, 130.63, 130.57, 125.67, 124.04, 122.03, 120.17, 115.80, 50.06, 36.92, 28.73, 24.80, 9.69. HRMS (ESI) calcd for C₁₉H₁₉N₂O [M+H]⁺ 291.1492, found 291.1489.

  5-Ethyl-1-methoxy-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]-isoquinolin-6(5H)-one (2c): Yellow solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝5:1) as eluent to give 2c (83% yield, 76 mg). m.p. 155~156 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.44~8.30 (m, 1H), 7.95~7.81 (m, 1H), 7.48 (t, J＝8.1 Hz, 1H), 7.43~7.33 (m, 2H), 7.07 (d, J＝7.9 Hz, 1H), 7.01 (d, J＝8.3 Hz, 1H), 4.10 (s, 3H), 2.45~2.32 (m, 1H), 2.03~1.89 (m, 1H), 1.71 (s, 3H), 0.55 (t, J＝7.3 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.28, 158.62, 148.07, 144.38, 144.26, 132.30, 130.18, 125.63, 125.54, 120.48, 118.39, 115.45, 112.59, 110.24, 56.63, 49.89, 36.96, 28.45, 9.53. HRMS (ESI) calcd for C₁₉H₁₉N₂O₂ [M+H]⁺ 307.1441, found 307.1449.

  1-Bromo-5-ethyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (2d): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝20:1) as eluent to give 2d (53% yield, 56 mg). m.p. 182~183 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.45~8.32 (m, 1H), 7.98~7.88 (m, 1H), 7.81 (d, J＝7.8 Hz, 1H), 7.53~7.40 (m, 3H), 7.35 (t, J＝7.9 Hz, 1H), 2.49~2.34 (m, 1H), 2.05~1.92 (m, 1H), 1.73 (s, 3H), 0.58 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.48, 147.51, 144.75, 143.74, 135.22, 131.33, 130.76, 126.40, 125.95, 125.70, 122.81, 121.40, 120.87, 115.73, 50.53, 36.97, 28.42, 9.63. HRMS (ESI) calcd for C₁₈H₁₆BrN₂O [M+H]⁺ 355.0441, found 355.0444.

  5-Ethyl-2, 5-dimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoquino- lin-6(5H)-one (2e): White solid. Isolated by by flash column chromatography (petroleum ether/ethyl acetate, V: V＝20:1) as eluent to give 2e (72% yield, 62 mg). m.p. 113~114 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.40~8.34 (m, 1H), 8.30 (s, 1H), 7.85~7.78 (m, 1H), 7.47~7.33 (m, 4H), 2.48~2.38 (m, 4H), 2.05~1.94 (m, 1H), 1.71 (s, 3H), 0.57 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.72, 150.30, 144.14, 138.82, 137.71, 133.11, 131.42, 126.11, 126.02, 125.93, 125.56, 123.04, 119.79, 115.79, 49.93, 36.44, 28.55, 21.05, 9.69. HRMS (ESI) calcd for C₁₉H₁₉N₂O [M+H]⁺ 291.1492, found 291.1497.

  2-Chloro-5-ethyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (2f): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝20:1) as eluent to give 2f (71% yield, 66 mg). m.p. 135~136 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.47 (d, J＝2.0 Hz, 1H), 8.41~8.31 (m, 1H), 7.88~7.76 (m, 1H), 7.53 (dd, J＝8.5, 1.9 Hz, 1H), 7.49~7.43 (m, 2H), 7.40 (d, J＝8.5 Hz, 1H), 2.53~2.37 (m, 1H), 2.05~1.92 (m, 1H), 1.72 (s, 3H), 0.58 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.89, 148.75, 144.02, 139.93, 134.04, 132.01, 131.39, 127.83, 126.20, 126.06, 125.57, 124.97, 120.10, 115.84, 50.07, 36.42, 28.41, 9.68. HRMS (ESI) calcd for C₁₈H₁₆ClN₂O [M+H]⁺ 311.0946, found 311.0940.

  5-Ethyl-3, 5-dimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoquino-lin-6(5H)-one (2g): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝20:1) as eluent to give 2g (91% yield, 79 mg). m.p. 144~145 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.43~8.30 (m, 2H), 7.80 (dd, J＝6.5, 2.0 Hz, 1H), 7.47~7.37 (m, 2H), 7.30 (d, J＝8.1 Hz, 1H), 7.25 (s, 1H), 2.55~2.36 (m, 4H), 2.08~1.94 (m, 1H), 1.72 (s, 3H), 0.58 (J, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.64, 150.34, 144.22, 142.54, 141.72, 131.36, 128.89, 126.59, 125.89, 125.87, 125.39, 120.70, 119.69, 115.73, 50.10, 36.55, 28.50, 22.12, 9.73. HRMS (ESI) calcd for C₁₉H₁₉N₂O [M+H]⁺ 291.1492, found 291.1490.

  5-Ethyl-3-methoxy-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso- quinolin-6(5H)-one (2h): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝20:1) as eluent to give 2h (79% yield, 72 mg). m.p. 82~83 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.41 (d, J＝8.7 Hz, 1H), 8.37~8.28 (m, 1H), 7.83~7.72 (m, 1H), 7.47~7.34 (m, 2H), 7.04 (dd, J＝8.7, 2.4 Hz, 1H), 6.94 (d, J＝2.4 Hz, 1H), 3.92 (s, 3H), 2.51~2.35 (m, 1H), 2.05~1.91 (m, 1H), 1.72 (s, 3H), 0.60 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.49, 162.78, 150.27, 144.34, 143.86, 131.35, 127.89, 125.87, 125.15, 119.48, 116.35, 115.66, 113.48, 111.86, 55.69, 50.36, 36.69, 28.58, 9.71. HRMS (ESI) calcd for C₁₉H₁₉N₂O₂ [M+H]⁺ 307.1441, found 307.1449.

  5-Ethyl-5-methyl-3-phenylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (2i): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 2i (60% yield, 72 mg). m.p. 151~152 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.56 (d, J＝8.2 Hz, 1H), 8.44~8.36 (m, 1H), 7.86 (dd, J＝6.3, 2.4 Hz, 1H), 7.73 (dd, J＝8.2, 1.6 Hz, 1H), 7.69~7.63 (m, 3 H), 7.54~7.41 (m, 5H), 2.55~2.44 (m, 1H), 2.17~2.03 (m, 1H), 1.80 (s, 3H), 0.64 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.43, 149.92, 144.85, 144.17, 142.18, 140.09, 131.38, 129.15, 128.40, 127.34, 126.78, 126.47, 126.01, 125.65, 124.77, 122.14, 119.81, 115.77, 50.35, 36.60, 28.50, 9.77. HRMS (ESI) calcd for C₂₄H₂₁- N₂O [M+H]⁺ 353.1648, found 353.1645.

  3-Bromo-5-ethyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (2j): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 2j (64% yield, 68 mg). m.p. 184~185 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.39~8.21 (m, 2H), 7.89~7.76 (m, 1H), 7.65~7.59 (m, 2H), 7.49~7.37 (m, 2H), 2.51~2.38 (m, 1H), 2.05~1.92 (m, 1H), 1.73 (s, 3H), 0.60 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.62, 149.19, 144.07, 143.54, 131.30, 129.43, 127.39, 126.62, 126.17, 125.94, 122.40, 119.97, 115.81, 50.23, 36.55, 28.32, 9.71. HRMS (ESI) calcd for C₁₈H₁₆BrN₂O [M+H]⁺ 355.0441, found 355.0449.

  5-Ethyl-3-iodo-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (2k): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝40:1) as eluent to give 2k (52% yield, 62 mg). m.p. 226~227 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.41~8.32 (m, 1H), 8.18 (d, J＝8.2 Hz, 1H), 7.87~7.73 (m, 3H), 7.50~7.39 (m, 2H), 2.50~2.38 (m, 1H), 2.05~1.92 (m, 1H), 1.72 (s, 3H), 0.60 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.54, 149.32, 144.06, 143.41, 137.10, 135.41, 131.36, 127.21, 126.17, 125.96, 122.92, 119.99, 115.81, 98.81, 50.04, 36.54, 28.30, 9.72. HRMS (ESI) calcd for C₁₈H₁₆IN₂O [M+H]⁺ 403.0302, found 403.0303.

  5-Ethyl-5-methyl-3-(trifluoromethyl)benzo^{[4, 5]}imidazo-[2, 1-a]isoquinolin-6(5H)-one (2l): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝40:1) as eluent to give 2l (76% yield, 78 mg). m.p. 163~164 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.61 (d, J＝8.2 Hz, 1H), 8.43~8.35 (m, 1H), 7.89~7.82 (m, 1H), 7.75 (d, J＝8.4 Hz, 1H), 7.71 (s, 1H), 7.52~7.44 (m, 2H), 2.55~2.43 (m, 1H), 2.11~1.98 (m, 1H), 1.77 (s, 3H), 0.60 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.52, 148.55, 144.11, 142.35, 133.55 (d, J＝32.8 Hz), 131.43, 126.61, 126.39, 126.34, 124.71 (d, J＝3.6 Hz), 123.80 (d, J＝272.9 Hz), 123.28 (d, J＝4.0 Hz), 120.31, 115.94, 50.43, 36.58, 28.23, 9.68. HRMS (ESI) calcd for C₁₉H₁₆F₃N₂O [M+H]⁺ 345.1209, found 345.1201.

  Methyl 5-ethyl-5-methyl-6-oxo-5, 6-dihydrobenzo^{[4, 5]}- imidazo [2, 1-a] isoquinoline-3-carboxylate (2m): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate＝20:1) as eluent to give 2m (83% yield, 83 mg). m.p. 168~169 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.54 (d, J＝8.2 Hz, 1H), 8.42~8.31 (m, 1H), 8.19~8.07 (m, 2H), 7.89~7.77 (m, 1H), 7.51~7.37 (m, 2H), 3.97 (s, 3H), 2.55~2.39 (m, 1H), 2.15~2.02 (m, 1H), 1.77 (s, 3H), 0.57 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 172.92, 166.31, 148.94, 144.09, 141.77, 132.97, 131.37, 128.64, 127.70, 127.11, 126.25, 126.22, 126.01, 120.19, 115.88, 52.69, 50.33, 36.47, 28.29, 9.69. HRMS (ESI) calcd for C₂₀H₁₉N₂O₃ [M+H]⁺ 335.1390, found 335.1393.

  5-Ethyl-5-methyl-3-(methylsulfonyl)benzo^{[4, 5]}imidazo-[2, 1-a]isoquinolin-6(5H)-one (2n): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝5:1) as eluent to give 2n (81% yield, 86 mg). m.p. 170~171 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.69 (d, J＝8.2 Hz, 1H), 8.39 (dd, J＝6.1, 3.0 Hz, 1H), 8.11~7.99 (m, 2H), 7.86 (dd, J＝6.0, 3.0 Hz, 1H), 7.55~7.42 (m, 2H), 3.15 (s, 3H), 2.55~2.43 (m, 1H), 2.13~2.02 (m, 1H), 1.79 (s, 3H), 0.59 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.17, 147.97, 144.05, 143.21, 142.97, 131.39, 128.19, 127.17, 126.74, 126.51, 125.55, 120.46, 115.97, 50.60, 44.59, 36.52, 28.17, 9.73. HRMS (ESI) calcd for C₁₉H₁₉N₂O₃S [M+H]⁺ 355.1111, found 355.1118.

  4-Ethyl-4-methylbenzo^{[4, 5]}imidazo[1, 2-a]thieno[2, 3-c]-pyridin-5(4H)-one (2o): Colorless oil. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 2o (63% yield, 53 mg). ¹H NMR (400 MHz, CDCl₃) δ: 8.36~8.30 (m, 1H), 7.79~7.73 (m, 1H), 7.61 (d, J＝5.1 Hz, 1H), 7.44~7.36 (m, 2H), 7.07 (d, J＝5.1 Hz, 1H), 2.46~2.33 (m, 1H), 2.01~1.89 (m, 1H), 1.68 (s, 3H), 0.62 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 174.07, 147.90, 146.99, 144.03, 131.04, 131.01, 130.82, 125.93, 125.60, 124.08, 119.73, 115.34, 50.34, 35.96, 27.80, 9.78. HRMS (ESI) calcd for C₁₆H₁₅N₂OS [M+H]⁺ 283.0900, found 283.0908.

  7-Ethyl-7-methylbenzo[h]benzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-8(7H)-one (2p): Yellow solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 2p (82% yield, 80 mg). m.p. 173~174 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 10.53 (d, J＝8.8 Hz, 1H), 8.54~8.40 (m, 1H), 8.04 (d, J＝8.7 Hz, 1H), 7.99~7.88 (m, 2H), 7.86~7.78 (m, 1H), 7.64 (t, J＝7.4 Hz, 1H), 7.57 (d, J＝8.7 Hz, 1H), 7.53~7.44 (m, 2H), 2.60~2.48 (m, 1H), 2.21~2.09 (m, 1H), 1.81 (s, 3H), 0.57 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.56, 150.23, 144.22, 142.28, 132.87, 132.80, 130.34, 128.79, 128.48, 128.13, 126.88, 125.94, 125.89, 123.16, 120.21, 118.58, 115.84, 50.40, 36.19, 28.65, 9.72. HRMS (ESI) calcd for C₂₂H₁₉N₂O [M+H]⁺ 327.1492, found 327.1498.

  5-Ethyl-1, 3, 5-trimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoqui-nolin-6(5H)-one (2q): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V: V＝30:1) as eluent to give 2q (67% yield, 61 mg). m.p. 104~105 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.43~8.35 (m, 1H), 7.86~7.77 (m, 1H), 7.46~7.36 (m, 2H), 7.13 (s, 2H), 3.01 (s, 3H), 2.45~2.35 (m, 4H), 2.05~1.94 (m, 1H), 1.71 (s, 3H), 0.58 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 173.80, 150.51, 144.37, 142.87, 140.92, 139.58, 132.09, 130.55, 125.59, 125.42, 124.60, 119.98, 119.40, 115.73, 49.95, 36.96, 28.80, 24.62, 21.79, 9.73. HRMS (ESI) calcd for C₂₀H₂₁N₂O [M+H]⁺ 305.1648, found 305.1640.

  1, 3-Dichloro-5-ethyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]-isoquinolin-6(5H)-one (2r): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 2r (55% yield, 57 mg). m.p. 167~168 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.38 (dd, J＝6.2, 2.8 Hz, 1H), 7.91 (dd, J＝6.3, 2.7 Hz, 1H), 7.58 (d, J＝1.8 Hz, 1H), 7.53~7.42 (m, 2H), 7.40 (d, J＝1.7 Hz, 1H), 2.50~2.35 (m, 1H), 2.02~1.90 (m, 1H), 1.74 (s, 3H), 0.61 (t, J＝7.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.79, 146.61, 145.80, 143.94, 136.95, 134.42, 131.23, 130.42, 126.63, 126.15, 125.43, 120.86, 120.20, 115.72, 50.50, 37.02, 28.32, 9.64. HRMS (ESI) calcd for C₁₈H₁₅Cl₂N₂O [M+H]⁺ 345.0556, found 345.0559.

  4.3   General procedure for the synthesis of 3

  2-Methyl-1-(2-phenyl-1H-benzo[d]imidazol-1-yl)prop-2-en-1-one (1a): (78.7 mg, 0.3 mmol) and BPO (145.3 mg, 2.0 equiv.) were mixtured in 3 mL CH₃NO₂, and then the mixture was refluxed at 120 ℃ in oil bath for 2 h. After the completion of the reaction, the mixture was quenched by NaHCO₃ (sat. aq. 15 mL) and extracted with CH₂Cl₂ (5 mL×3). Then the organic solvent was concentrated in vacuo. The residue was purified by flash column chromatography with ethyl acetate and petroleum ether as eluent to give 3a.

  5-Benzyl-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]isoquinolin-6(5H)-one (3a): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝30:1) as eluent to give 3a (60% yield, 61 mg). m.p. 147~148 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.37~8.31 (m, 1H), 8.28 (d, J＝7.7 Hz, 1H), 7.70~7.65 (m, 1H), 7.64~7.55 (m, 2H), 7.50~7.43 (m, 1H), 7.42~7.33 (m, 2H), 6.89 (t, J＝7.4 Hz, 1H), 6.81 (t, J＝7.4 Hz, 2H), 6.53 (d, J＝7.3 Hz, 2H), 3.56 (d, J＝13.0 Hz, 1H), 3.17 (d, J＝13.0 Hz, 1H), 1.94 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.74, 149.60, 143.86, 140.76, 135.09, 131.60, 131.13, 129.07, 127.95, 127.87, 127.15, 126.70, 125.79, 125.73, 125.52, 123.65, 119.72, 115.51, 51.20, 50.95, 26.09. HRMS (ESI) calcd for C₂₃H₁₉N₂O [M+H]⁺ 339.1492, found 339.1493.

  5-Benzyl-1, 5-dimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoqui-nolin-6(5H)-one (3b): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V: V＝40:1) as eluent to give 3b (61% yield, 64 mg). m.p. 112~113 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.37 (d, J＝7.6 Hz, 1H), 7.71 (d, J＝7.4 Hz, 1H), 7.45 (d, J＝3.9 Hz, 2H), 7.39 (dd, J＝6.6, 5.5 Hz, 2H), 7.30 (t, J＝4.2 Hz, 1H), 6.90 (t, J＝7.0 Hz, 1H), 6.79 (t, J＝7.5 Hz, 2H), 6.50 (d, J＝7.8 Hz, 2H), 3.51 (d, J＝13.0 Hz, 1H), 3.13 (d, J＝13.0 Hz, 1H), 2.90 (s, 3H), 1.94 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.84, 149.77, 144.04, 141.76, 139.49, 135.24, 131.17, 130.34, 130.27, 129.16, 127.71, 127.09, 125.55, 125.46, 124.47, 122.45, 120.01, 115.50, 51.51, 51.11, 26.15, 24.45. HRMS (ESI) calcd for C₂₄H₂₁N₂O [M+H]⁺ 353.1648, found 353.1643.

  5-Benzyl-1-methoxy-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]-isoquinolin-6(5H)-one (3c): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝10:1) as eluent to give 3c (76% yield, 84 mg). m.p. 163~164 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.34 (d, J＝7.0 Hz, 1H), 7.75 (d, J＝6.9 Hz, 1H), 7.54 (t, J＝8.1 Hz, 1H), 7.44~7.30 (m, 2H), 7.22 (d, J＝7.9 Hz, 1H), 7.02 (d, J＝8.3 Hz, 1H), 6.88 (t, J＝7.3 Hz, 1H), 6.78 (t, J＝7.5 Hz, 2H), 6.52 (d, J＝7.3 Hz, 2H), 4.05 (s, 3H), 3.53 (d, J＝13.0 Hz, 1H), 3.14 (d, J＝13.0 Hz, 1H), 1.93 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.63, 158.47, 147.67, 144.23, 143.38, 135.03, 131.97, 130.06, 128.96, 127.85, 127.28, 125.58, 125.42, 120.44, 119.00, 115.25, 113.12, 110.55, 56.69, 51.38, 51.00, 26.41. HRMS (ESI) calcd for C₂₄H₂₁N₂O₂ [M+H]⁺ 369.1598, found 369.1599.

  5-Benzyl-3, 5-dimethylbenzo^{[4, 5]}imidazo[2, 1-a]isoqui-nolin-6(5H)-one (3d): Yellow solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V: V＝20:1) as eluent to give 3d (69% yield, 73 mg). m.p. 92~93 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.37~8.28 (m, 1H), 8.17 (d, J＝8.0 Hz, 1H), 7.68 (dd, J＝6.0, 3.0 Hz, 1H), 7.42~7.34 (m, 3H), 7.32~7.27 (m, 1H), 6.91 (t, J＝7.3 Hz, 1H), 6.83 (t, J＝7.5 Hz, 2H), 6.55 (d, J＝7.4 Hz, 2H), 3.54 (d, J＝13.0 Hz, 1H), 3.18 (d, J＝13.0 Hz, 1H), 2.52 (s, 3H), 1.93 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.88, 149.87, 143.90, 142.12, 140.80, 135.18, 131.10, 129.71, 129.15, 129.02, 127.85, 127.16, 127.13, 125.72, 125.29, 121.00, 119.54, 115.44, 51.12, 50.93, 26.02, 22.15. HRMS (ESI) calcd for C₂₄H₂₁N₂O [M+H]⁺ 353.1648, found 353.1648.

  5-Benzyl-3-methoxy-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]isoquinolin-6(5H)-one (3e): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝25:1) as eluent to give 3e (79% yield, 87 mg). m.p. 112~113 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.30 (dd, J＝5.9, 3.3 Hz, 1H), 8.21 (d, J＝8.3 Hz, 1H), 7.64 (dd, J＝5.8, 3.2 Hz, 1H), 7.39~7.31 (m, 2H), 7.04~6.98 (m, 2H), 6.92 (t, J＝7.2 Hz, 1H), 6.84 (t, J＝7.5 Hz, 2H), 6.59 (d, J＝7.5 Hz, 2H), 3.92 (s, 3H), 3.53 (d, J＝13.0 Hz, 1H), 3.15 (d, J＝13.0 Hz, 1H), 1.91 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.77, 162.39, 149.80, 144.03, 142.84, 135.14, 131.09, 129.18, 127.91, 127.68, 127.18, 125.68, 125.04, 119.33, 116.60, 115.37, 113.68, 112.34, 55.70, 51.31, 50.89, 26.13. HRMS (ESI) calcd for C₂₄H₂₁N₂O₂ [M+H]⁺ 369.1598, found 369.1589.

  5-Benzyl-1-fluoro-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-one (3f): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝10:1) as eluent to give 3f (30% yield, 32 mg). m.p. 144~145 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.36 (dd, J＝6.9, 1.7 Hz, 1H), 7.79 (dd, J＝6.8, 1.7 Hz, 1H), 7.61~7.54 (m, 1H), 7.46~7.36 (m, 3H), 7.25~7.18 (m, 1H), 6.91 (t, J＝7.4 Hz, 1H), 6.81 (t, J＝7.5 Hz, 2H), 6.52 (d, J＝7.2 Hz, 2H), 3.57 (d, J＝13.0 Hz, 1H), 3.15 (d, J＝13.0 Hz, 1H), 1.95 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 172.12, 160.33 (d, J＝262.3 Hz), 144.18, 144.16, 143.36, 134.77, 132.14 (d, J＝9.6 Hz), 130.16, 128.99, 128.04, 127.44, 126.01 (d, J＝21.4 Hz), 122.65 (d, J＝3.7 Hz), 120.57, 115.80 (d, J＝21.3 Hz), 115.42, 113.13 (d, J＝9.7 Hz), 51.34, 51.20, 26.27. HRMS (ESI) calcd for C₂₃H₁₈F- N₂O [M+H]⁺ 357.1398, found 357.1391.

  5-Benzyl-1-chloro-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]iso-quinolin-6(5H)-on (3g): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝10:1) as eluent to give 3g (46% yield, 51 mg). m.p. 142~143 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.41~8.31 (m, 1H), 7.84~7.75 (m, 1H), 7.58~7.51 (m, 2H), 7.48 (d, J＝7.7 Hz, 1H), 7.46~7.37 (m, 2H), 6.92 (t, J＝7.4 Hz, 1H), 6.80 (t, J＝7.6 Hz, 2H), 6.49 (d, J＝7.2 Hz, 2H), 3.52 (d, J＝13.0 Hz, 1H), 3.11 (d, J＝13.0 Hz, 1H), 1.95 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 171.93, 148.72, 143.79, 142.58, 134.64, 131.38, 131.06, 129.93, 129.07, 128.01, 127.36, 127.15, 126.11, 125.98, 125.82, 122.68, 119.84, 115.50, 51.22, 51.02, 25.74. HRMS (ESI) calcd for C₂₃H₁₈ClN₂O [M+H]⁺ 373.1102, found 373.1109.

  5-Benzyl-3-chloro-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]-isoquinolin-6(5H)-one (3h): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝10:1) as eluent to give 3h (53% yield, 59 mg). m.p. 131~132 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.32 (dd, J＝6.0, 2.8 Hz, 1H), 8.20 (d, J＝8.4 Hz, 1H), 7.67 (dd, J＝6.0, 2.8 Hz, 1H), 7.54 (d, J＝2.0 Hz, 1H), 7.45~7.34 (m, 3H), 6.91 (t, J＝7.4 Hz, 1H), 6.82 (t, J＝7.5 Hz, 2H), 6.55 (d, J＝7.3 Hz, 2H), 3.55 (d, J＝13.1 Hz, 1H), 3.13 (d, J＝13.1 Hz, 1H), 1.92 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.99, 148.65, 143.81, 142.46, 137.74, 134.67, 131.07, 129.06, 128.49, 128.00, 127.35, 127.09, 126.94, 125.95, 125.77, 122.29, 119.82, 115.49, 51.27, 51.00, 25.77. HRMS (ESI) calcd for C₂₃H₁₈ClN₂O [M+ H]⁺ 373.1102, found 373.1100.

  5-Benzyl-3-bromo-5-methylbenzo^{[4, 5]}imidazo[2, 1-a]-isoquinolin-6(5H)-one (3i): White solid. Isolated by flash column chromatography (petroleum ether/ethyl acetate, V:V＝10:1) as eluent to give 3i (45% yield, 56 mg). m.p. 145~146 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.38~8.27 (m, 1H), 8.12 (d, J＝8.4 Hz, 1H), 7.73~7.63 (m, 2H), 7.59 (dd, J＝8.4, 1.8 Hz, 1H), 7.46~7.33 (m, 2H), 6.91 (t, J＝7.4 Hz, 1H), 6.83 (t, J＝7.5 Hz, 2H), 6.54 (d, J＝7.3 Hz, 2H), 3.54 (d, J＝13.1 Hz, 1H), 3.13 (d, J＝13.1 Hz, 1H), 1.92 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.93, 148.72, 143.79, 142.58, 134.64, 131.38, 131.06, 129.93, 129.07, 128.01, 127.36, 127.15, 126.11, 125.98, 125.82, 122.68, 119.84, 115.50, 51.22, 51.02, 25.74. HRMS (ESI) calcd for C₂₃H₁₈BrN₂O [M+H]⁺ 417.0597, found 417.0591.

  5-Benzyl-5-methyl-6-oxo-5, 6-dihydrobenzo^{[4, 5]}imidazo- [2, 1-a]isoquinoline-3-carbonitrile (3j): White solid. Isolated by flash column chromatography (petroleum ether/ ethyl acetate, V:V＝10:1) as eluent to give 3j (40% yield, 43 mg). m.p. 131~132 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 8.35 (dd, J＝7.6, 3.3 Hz, 2H), 7.84 (s, 1H), 7.72 (dd, J＝7.7, 2.1 Hz, 2H), 7.51~7.38 (m, 2H), 6.92 (t, J＝7.4 Hz, 1H), 6.82 (t, J＝7.5 Hz, 2H), 6.49 (d, J＝7.4 Hz, 2H), 3.59 (d, J＝13.2 Hz, 1H), 3.12 (d, J＝13.2 Hz, 1H), 1.96 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ: 171.46, 147.54, 143.81, 143.79, 141.60, 134.28, 131.16, 131.14, 130.87, 128.99, 128.16, 127.62, 127.59, 126.64, 126.38, 120.33, 118.25, 115.67, 114.73, 51.27, 51.11, 25.52. HRMS (ESI) calcd for C₂₄H₁₈N₃O [M+H]⁺ 364.1444, found 364.1450.

  Supporting Information ¹H NMR and ¹³C NMR spectra for compounds 2 and 3. The Supporting Information is available free of charge via the Internet at http://sioc-joural.cn/.

  
  
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• 

  图式 1  Synthesis of benzimidazo-isoquinoline frameworks

  下载: 全尺寸图片 幻灯片
  

  图式 2  Plausible catalytic cycle

  下载: 全尺寸图片 幻灯片

  表 1  Survey of the reaction conditions^{a, b}

  Entry	Oxidant	Catalyst (mol%)	Solvent	Yield/%
  1	DCP	None	CH3CN	23
  2	TBHP	None	CH3CN	Trace
  3	DTBP	None	CH3CN	0
  4	TBPB	None	CH3CN	51
  5	TBPB	None	DMSO	23
  6	TBPB	None	CH3NO2	63
  7	TBPB	None	THF	0
  8	TBPB	None	DCE	39
  9	TBPB	None	EtOAc	0
  10	TBPB	FeCl2 (20)	CH3NO2	45
  11	TBPB	FeCl3 (20)	CH3NO2	26
  12	TBPB	Fe(OTf)3 (20)	CH3NO2	Trace
  13	TBPB	Cp2Fe (20)	CH3NO2	84
  14	TBPB	Cp2Fe (15)	CH3NO2	82
  15	TBPB	Cp2Fe (10)	CH3NO2	83
  16	TBPB	Cp2Fe (5)	CH3NO2	74
  17	TBPB	Cp2Fe (10)	CH3NO2	80c
  18	TBPB	Cp2Fe (10)	CH3NO2	45d
  19	TBPB	Cp2Fe (10)	CH3NO2	11e
  a Reactions were carried out with 1a (0.3 mmol), peroxides (2.0 equiv.), catalyst (5~20 mol%) and solvent (2 mL) refluxed at 120 ℃ for 1 h. b Yield of the isolated product. c Reaction performed at 120 ℃ for 6 h. d Reaction performed at 90 ℃ for 6 h. e Reaction performed at 60 ℃ for 6 h.

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  表 2  Substrate scope^{a, b}

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  表 3  Substrate scope^{a, b}

  下载: 导出CSV
•