Efficient Synthesis of Fluorene Derivatives by Benzannulation of Indene Dienes with Benzoylacetonitrile Catalyzed by Lipase

Wenhan Shi; Yiyao Wang; Fengxi Li; Hanqing Xie; Lei Wang; Rui Zhao; Zhi Wang

doi:10.1055/a-2341-9274

Synlett, Table of Contents

Synlett 2025; 36(04): 402-406
DOI: 10.1055/a-2341-9274

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Efficient Synthesis of Fluorene Derivatives by Benzannulation of Indene Dienes with Benzoylacetonitrile Catalyzed by Lipase

Wenhan Shi

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

,

Yiyao Wang

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

^cCollege of Life Science, Jilin Agricultural University, Changchun, 130118, P. R. of China

,

Fengxi Li

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

,

Hanqing Xie

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

,

Lei Wang

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

,

Rui Zhao∗

^bChina–Japan Union Hospital of Jilin University, Changchun 130000, P. R. of China

,

Zhi Wang∗

^aKey Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130023, P. R. of China

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Abstract

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Abstract

An enzymatic method was developed for the synthesis of fluorene derivatives by benzannulation of indene dienes with benzoylacetonitrile in a nonaqueous solvent. Under the optimal reaction condition [indene diene (0.5 mmol), benzoylacetonitrile (0.5 mmol), ethanol (2 mL), lipase from porcine pancreas (5 mg), 50 °C, 24 h], fluorenes bearing various groups were obtained in satisfactory yields (83–93%). This method not only offers a significant advancement in the synthesis of fluorene derivatives, but also represents a new application of lipase in promiscuous enzyme catalysis.

Key words

lipase - fluorene - indene dienes - benzoylacetonitrile - enzymic catalysis

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References

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44 Fluorene Derivatives 3a–k; General Procedure The appropriate indene diene 1 (0.5 mmol), benzoylacetonitrile (2; 0.5 mmol), and PPL (5 mg) were added to EtOH (2 mL), and the mixture was stirred at 50 °C in a shaker until the reaction was complete (TLC). The product was then purified by flash column chromatography [silica gel, PE–EtOAc (2:1 to 10:1)]. 3-Amino-1-phenyl-9H-fluorene-2,4-dicarbonitrile (3a) Fluorescent solid; yield: 93%. ¹H NMR (400 MHz, DMSO-d₆): δ = 3.72 (s, 2 H), 6.78 (s, 2 H), 7.53–7.60 (m, 8 H), 8.28 (d, J = 7.56 Hz, 1 H). 3-Amino-1-(3-methylphenyl)-9H-fluorene-2,4-dicarbonitrile (3b) Fluorescent solid; yield: 86%. ¹H NMR (400 MHz, DMSO-d₆): δ = 3.72 2.42 (s, 3 H), 3.71 (s, 2 H), 6.75 (s, 2 H), 7.34–7.74 (m, 6 H), 8.42 (d, J = 8.08 Hz, 2 H). The NMR spectra of the products were identical to those previously reported.19

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