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. 2021 Dec 13;13(1):263-273.
doi: 10.1039/d1sc03865f. eCollection 2021 Dec 22.

Cu(i) catalysis for selective condensation/bicycloaromatization of two different arylalkynes: direct and general construction of functionalized C-N axial biaryl compounds

Qian Shang  1 , Haifang Tang  1 , Yongping Liu  2 , MingMing Yin  2 , Lebin Su  1 , Shimin Xie  1 , Lixin Liu  1 , Wen Yang  1 , Yi Chen  2 , Jianyu Dong  3 , Yongbo Zhou  1 , Shuang-Feng Yin  1
Affiliations

Cu(i) catalysis for selective condensation/bicycloaromatization of two different arylalkynes: direct and general construction of functionalized C-N axial biaryl compounds

Qian Shang et al. Chem Sci. .

Abstract

Selective condensation/bicycloaromatization of two different arylalkynes is firstly developed under ligand-free copper(i)-catalysis, which allows the direct synthesis of C-N axial biaryl compounds in high yields with excellent selectivity and functional group tolerance. Due to the critical effects of Cu(i) catalyst and HFIP, many easily occurring undesired reactions are suppressed, and the coupled five-six aromatic rings are constructed via the selective formation of two C(sp2)-N(sp2) bonds and four C(sp2)-C(sp2) bonds. The achievement of moderate enantioselectivity verifies its potential for the simplest asymmetric synthesis of atropoisomeric biaryls. Western blotting demonstrated that the newly developed compounds are promising targets in biology and pharmaceuticals. This unique reaction can construct structurally diverse C-N axial biaryl compounds that have never been reported by other methods, and might be extended to various applications in materials, chemistry, biology, and pharmaceuticals.

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Conflict of interest statement

The authors declare that there are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Strategies to construct biaryl compounds.
Fig. 1
Fig. 1. Biologically active 1,1′-naphthylindole derivatives.
Scheme 2
Scheme 2. Condensation/bicycloaromatization of o-amino and o-carbonyl arylalkynes.
Scheme 3
Scheme 3. Substrate scope.
Scheme 4
Scheme 4. Scope of heteroaryl alkynes. aReaction conditions: a (0.05 mmol), b (1.2 equiv., 0.06 mmol), CuI (10 mol%), Cs2CO3 (2.0 equiv.), HFIP (1.0 mL), 100 °C, 24 h, N2. Isolated yields are provided.
Scheme 5
Scheme 5. Control experiments.
Scheme 6
Scheme 6. Possible reaction mechanism.
Scheme 7
Scheme 7. Substrate scope of axially chiral compounds. Reaction conditions: (1) a (0.2 mmol), 4b (1.2 equiv.), CuI (5 mol%), Cs2CO3 (2.0 equiv.) HFIP, 80 °C, 50 min; (2) PdCl2 (5 mol%), L (6 mol%) HFIP, 80 °C, 15 h.
Fig. 2
Fig. 2. BV2 cells were pretreated with 10 μM A1 for 2 h and then treated with LPS (100 ng mL−1) for 6 h. (a) The levels of P65 and the corresponding phosphorylated form were measured by western blotting (n = 3 per group). Compared with the control group, **P < 0.01, vs. LPS group, *P < 0.05. (b) BV2 cells were pretreated with different concentrations (5–20 μM) of A1 for 2 h and were then treated with 100 ng mL−1 LPS for 6 h. The levels of IL-6 were detected by western blotting (A1 = 15c).
See this image and copyright information in PMC

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