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. 2020 Aug 26;10(52):31570-31574.
doi: 10.1039/d0ra06580c. eCollection 2020 Aug 21.

Ruthenium-catalyzed, site-selective C-H activation: access to C5-substituted azaflavanone

Manickam Bakthadoss  1 , Tadiparthi Thirupathi Reddy  1 , Duddu S Sharada  2
Affiliations

Ruthenium-catalyzed, site-selective C-H activation: access to C5-substituted azaflavanone

Manickam Bakthadoss et al. RSC Adv. .

Abstract

A site-selective ruthenium-catalyzed keto group assisted C-H bond activation of 2-aryl tetrahydroquinoline (azaflavanone) derivatives has been achieved with a variety of alkenes for the first time. A wide range of substrates was utilized for the synthesis of a wide variety of alkenylated azaflavanones. This simple and efficient protocol provides the C5-substituted azaflavanone derivatives in high yields with a broad range of functional group tolerance. Further, the C5-alkenylated products were converted into substituted 2-aryl quinoline derivatives in good yields.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Comparison between previous reports and our work.
Fig. 2
Fig. 2. ORTEP diagram of compound 3b.
Scheme 1
Scheme 1. Screening of various alkenes with 2 phenyl tetrahydroquinoline.a,b aReaction conditions: 1a (0.2 mmol), 2a–m (0.4 mmol), [{Ru(p-cymene)Cl2}2] (5 mol%), Cu(OAc)2 (50 mol%), AgSbF6 (20 mol%), DCE solvent at 100 °C, 5 h. bIsolated yields.
Scheme 2
Scheme 2. Substrate scope of azaflavanone derivatives with methyl acrylate.a,b aReaction conditions: 1b–h (0.2 mmol), 2a (0.4 mmol), [{Ru(p-cymene)Cl2}2] (5 mol%), Cu(OAc)2 (50 mol%), AgSbF6 (20 mol%), DCE solvent at 100 °C, 5 h. bIsolated yields.
Scheme 3
Scheme 3. Substrate scope of C6, C8 dibromo substituted azaflavanone with alkene.
Scheme 4
Scheme 4. Gram scale synthesis.
Scheme 5
Scheme 5. Competitive reactions.
Scheme 6
Scheme 6. Control experiment for directing group and alkyne.
Scheme 7
Scheme 7. Synthesis of alkyl (E)-3-(4-methoxy-2-phenylquinolin-5-yl) acrylate.
Scheme 8
Scheme 8. Selective alkene reduction of C5-coupled 2-phenyl tetrahydroquinoline 3o.
Scheme 9
Scheme 9. Proposed catalytic cycle for the C5-alkenylation of 2-aryl tetrahydroquinoline.
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