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Volumn 74, Issue 13, 2009, Pages 4720-4726

Palladium-catalyzed direct synthesis of carbazoles via one-pot N-arylation and oxidative biaryl coupling: Synthesis and mechanistic study

Author keywords

[No Author keywords available]

Indexed keywords

CATALYTIC SYSTEM; CHEMICAL EQUATIONS; DIARYLAMINE; DIRECT SYNTHESIS; KINETIC ISOTOPE EFFECTS; MECHANISTIC STUDIES; N-ARYLATION; ONE POT; OXIDATIVE COUPLINGS; REACTION INTERMEDIATE; SUBSTITUENT EFFECT;

EID: 67649576709     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9003376     Document Type: Article
Times cited : (154)

References (122)
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    • For pioneering work for oxidative biaryl coupling mediated by palladium, see: Yoshimoto, H.; Itatani, H. Bull. Chem. Soc. Jpn. 1973, 46, 2490-2492.
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    • For related oxidative carbazole syntheses, see
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    • For related palladium-catalyzed or -mediated oxidative C-H functionalization, see: (a) Fujiwara, Y.; Asano, R.; Moritani, I.; Teranishi, S. J. Org. Chem. 1976, 41, 1681-1683.
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    • A portion of this study was already reported in a preliminary communication
    • A portion of this study was already reported in a preliminary communication: Watanabe, T.; Ueda, S.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H. Chem. Commun. 2007, 4516-4518.
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    • Quite recently, it has been reported that pivalic acid works well as the reaction solvent for oxidative biaryl coupling, see ref 10c
    • Quite recently, it has been reported that pivalic acid works well as the reaction solvent for oxidative biaryl coupling, see ref 10c.
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    • Indeed, the treatment of diphenylamine in AcOH under oxygen atomosphere with palladium dichloride or palladium acetate/tetrabutylammonium bromide led to recovery of the starting material
    • Indeed, the treatment of diphenylamine in AcOH under oxygen atomosphere with palladium dichloride or palladium acetate/tetrabutylammonium bromide led to recovery of the starting material.
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    • Ligand screening for N-arylation is given in the Supporting Information
    • Ligand screening for N-arylation is given in the Supporting Information.
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    • When N-methyl anisidine was used, the corresponding N-methyl carbazole was obtained in ca. 7% yield. In this case, demethylated carbazole was formed in ca. 3% yield as a byproduct under the oxidative coupling process. Use of N-phenylaniline (diphenylamine) in place of aniline was ineffective in the oxidative coupling step after N-arylation
    • When N-methyl anisidine was used, the corresponding N-methyl carbazole was obtained in ca. 7% yield. In this case, demethylated carbazole was formed in ca. 3% yield as a byproduct under the oxidative coupling process. Use of N-phenylaniline (diphenylamine) in place of aniline was ineffective in the oxidative coupling step after N-arylation.
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    • High reactivity of electron-rich carbazoles was described in ref 10c
    • High reactivity of electron-rich carbazoles was described in ref 10c.
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    • Almost the same results were obtained when the one-pot N-arylation-oxidative coupling was performed separately. For example, the stepwise reactions of 1a and 2c gave 70% yield of 5ea in 2 steps (compare with entry 19: 66%). The stepwise and one-pot reaction of 1e and 2a also gave comparable results (69% and 64%, respectively, see entry 6). (Chemical Equation Presented)
    • Almost the same results were obtained when the one-pot N-arylation-oxidative coupling was performed separately. For example, the stepwise reactions of 1a and 2c gave 70% yield of 5ea in 2 steps (compare with entry 19: 66%). The stepwise and one-pot reaction of 1e and 2a also gave comparable results (69% and 64%, respectively, see entry 6). (Chemical Equation Presented)
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    • Although the exact reason for the positive effect of an electronwithdrawing group at the para position on the carbazole formation is unclear, the increased acidity of the releasing proton may be one possible explanation
    • Although the exact reason for the positive effect of an electronwithdrawing group at the para position on the carbazole formation is unclear, the increased acidity of the releasing proton may be one possible explanation.
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    • In the coupling reaction with 1j, 3-aminoacetophenone 2l and 3-fluoroaniline 2m showed similar regioselectivity to 2j, although the product yields were lower
    • In the coupling reaction with 1j, 3-aminoacetophenone 2l and 3-fluoroaniline 2m showed similar regioselectivity to 2j, although the product yields were lower.
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    • It is likely that this biaryl coupling reaction needs to keep a balance between both electron-donating and -withdrawing groups. Thus, electron-withdrawing groups can (1) facilitate path E (σ-bond methathesis) by increasing the acidity of aromatic C-H protons, (2) decrease nucleophilicity of the aromatic carbon (when meta-substituted ones), and (3) stabilize the arylpalladium complex B (Scheme 5) by coordination (when there is an o-methoxycarbonyl group), and (4) stabilize the carbazoles. On the other hand, electron-donating groups can (1) decrease the acidity of the aromatic proton to suppress path E (σ-bond methathesis), (2) increase the nucleophilicity of the aromatic carbon, and (3) destabilize the carbazoles. We would like to express our sincere appreciation to the reviewer
    • It is likely that this biaryl coupling reaction needs to keep a balance between both electron-donating and -withdrawing groups. Thus, electron-withdrawing groups can (1) facilitate path E (σ-bond methathesis) by increasing the acidity of aromatic C-H protons, (2) decrease nucleophilicity of the aromatic carbon (when meta-substituted ones), and (3) stabilize the arylpalladium complex B (Scheme 5) by coordination (when there is an o-methoxycarbonyl group), and (4) stabilize the carbazoles. On the other hand, electron-donating groups can (1) decrease the acidity of the aromatic proton to suppress path E (σ-bond methathesis), (2) increase the nucleophilicity of the aromatic carbon, and (3) destabilize the carbazoles. We would like to express our sincere appreciation to the reviewer.
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    • The carbopalladation intermediate would have the wrong stereochemistry for the well-accepted syn-elimination of H-Pd-OAc. However, a stereomutation of the benzylic proton or anti-elimination cannot be completely ruled out, see: (a) Grigg, R.; Sridharan, V.; Stevenson, P.; Sukirthalingam, S.; Worakun, T. Tetrahedron 1990, 46, 4003-4018.
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    • The structure of 7 was confirmed by comparison of its spectral data with the authentic sample prepared by a separete route, see the Supporting Information
    • The structure of 7 was confirmed by comparison of its spectral data with the authentic sample prepared by a separete route, see the Supporting Information.
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    • The possibility that 3-phenylacrylate present in the reaction mixture might affect the reactivity of the palladium catalyst cannot be ruled out
    • The possibility that 3-phenylacrylate present in the reaction mixture might affect the reactivity of the palladium catalyst cannot be ruled out.
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    • The first palladation at the fluorobenzene moiety followed by 1,4-palladium shift might be possible. However, the palladium shift process would produce a regioisomeric mixture, see
    • The first palladation at the fluorobenzene moiety followed by 1,4-palladium shift might be possible. However, the palladium shift process would produce a regioisomeric mixture, see: (a) Campo, M. A.; Zhang, H.; Yao, T.; Ibdah, A.; McCulla, R. D.; Huang, Q.; Zhao, J.; Jenks, W. S.; Larock, R. C. J. Am. Chem. Soc. 2007, 129, 6298-6307.
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    • Campo, M.A.1    Zhang, H.2    Yao, T.3    Ibdah, A.4    McCulla, R.D.5    Huang, Q.6    Zhao, J.7    Jenks, W.S.8    Larock, R.C.9
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    • For synthesis of 4b-d, see the Supporting Information
    • For synthesis of 4b-d, see the Supporting Information.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.