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SCIENCE CHINA Chemistry, Volume 63 , Issue 8 : 1091-1099(2020) https://doi.org/10.1007/s11426-020-9754-7

Highly stereoselective construction of polycyclic benzofused tropane scaffolds and their latent bioactivities: bifunctional phosphonium salt-enabled cyclodearomatization process

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  • ReceivedMar 23, 2020
  • AcceptedApr 22, 2020
  • PublishedMay 19, 2020

Abstract


Funded by

the National Natural Science Foundation of China(21971165,21921002,81630101)

the National Key Reesarch and Development Program of China(2018YFA0903500)

the “1000-Youth Talents Program”(YJ201702)

the Fundamental Research Funds for the Central Universities.


Acknowledgment

This work was supported by the National Natural Science Foundation of China (21971165, 21921002, 81630101), the National Key Research and Development Program of China (2018YFA0903500), the “1000-Youth Talents Program” (YJ201702) and the Fundamental Research Funds for the Central Universities. We also acknowledge the comprehensive training platform of the Specialized Laboratory in the College of Chemistry at Sichuan University and the Analytical & Testing Center of Sichuan University for compound testing.


Interest statement

The authors declare that they have no conflict of interest.


Supplement

Supporting information

The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.


References

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  • Figure 1

    Selected bioactive molecules possessing benzofused tropane cores and asymmetric construction of such ring systems (color online)

  • Figure 2

    Scaled-up synthesis of 3l (a) and synthetic manipulations of product 3l (b).

  • Figure 3

    The cytotoxicity of representative products against different cancer cells and normal cells (color online).

  • Figure 4

    Mechanistic studies and plausible stereocontrol models for this cyclodearomatization (color online).

  • Table 1   Table 1 Optimization of reaction conditionsa)

    Entry

    Cat.

    Sol.

    Base

    Yield (%)b)

    drc)

    er (%)d)

    1

    P1

    Toluene

    Cs2CO3

    76

    >20:1

    53:47

    2

    P2

    Toluene

    Cs2CO3

    80

    >20:1

    54:46

    3

    P3

    Toluene

    Cs2CO3

    84

    >20:1

    56:44

    4

    P4

    Toluene

    Cs2CO3

    82

    >20:1

    58:42

    5

    P5

    Toluene

    Cs2CO3

    83

    >20:1

    66:34

    6

    P6

    Toluene

    Cs2CO3

    82

    >20:1

    70:30

    7

    P7

    Toluene

    Cs2CO3

    74

    >20:1

    66:34

    8

    P8

    Toluene

    Cs2CO3

    82

    >20:1

    74:26

    9

    P9

    Toluene

    Cs2CO3

    85

    >20:1

    72:28

    10

    P10

    Toluene

    Cs2CO3

    84

    >20:1

    82:18

    11

    P11

    Toluene

    Cs2CO3

    85

    >20:1

    89:11

    12

    P12

    Toluene

    Cs2CO3

    83

    >20:1

    86:14

    13

    P11

    Et2O

    K2CO3

    93

    >20:1

    94:6

    14e)

    P11

    Et2O

    K2CO3

    94

    >20:1

    96:4

    15e),f)

    P11

    Et2O

    K2CO3

    94

    >20:1

    96:4

    Reaction conditions: 1a (0.06 mmol), 2a (0.05 mmol), base (0.1 mmol) and catalyst (10 mol%) in solvent (0.5 mL) at room temperature for 12 h. b) Isolated yield. c) The dr value was determined by 1H nuclear magnetic resonance spectroscopy (1H NMR) and high performance liquid chromatography (HPLC) analysis. d) Determined by HPLC analysis on a chiral stationary phase. e) Et2O (1.0 mL) was used. f) With 5 mol% catalyst P11 for 24 h. Ts=4-toluenesulfonyl, TPS=triphenylsilyl.

  • Table 2   Table 2 Scope of 2-nitrobenzofuransa)

    Reaction conditions: 1a (0.12 mmol), 2 (0.1 mmol), base (0.2 mmol) and catalyst P11 (5 mol%) in Et2O (2.0 mL) at room temperature for 24 h. Isolated yields. The er value was determined by HPLC analysis on a chiral stationary phase and the dr value was determined by 1H NMR and HPLC analysis.

  • Table 3   Table 3 Scope of cyclic azomethine ylidesa)

    Reaction conditions: 1 (0.12 mmol), 2l (0.1 mmol), base (0.2 mmol) and catalyst P11 (5 mol%) in Et2O (2.0 mL) at room temperature for 24 h. Isolated yields. The er value was determined by HPLC analysis on a chiral stationary phase and the dr value was determined by 1H NMR and HPLC analysis.

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