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. 2018 Sep 10;8(55):31603-31607.
doi: 10.1039/c8ra06826g. eCollection 2018 Sep 5.

Acid-promoted iron-catalysed dehydrogenative [4 + 2] cycloaddition for the synthesis of quinolines under air

Jinfei Yang  1 , Xiao Meng  1 , Kai Lu  1 , Zhihao Lu  1 , Minliang Huang  1 , Chengniu Wang  1 , Fei Sun  1
Affiliations

Acid-promoted iron-catalysed dehydrogenative [4 + 2] cycloaddition for the synthesis of quinolines under air

Jinfei Yang et al. RSC Adv. .

Abstract

An acid-promoted iron-catalysed dehydrogenative [4 + 2] cycloaddition reaction was developed for the synthesis of quinolines using air as a terminal oxidant. Acetic acid was the best cocatalyst for the cycloaddition of N-alkyl anilines with alkenes or alkynes under air. Various quinoline derivatives were obtained in satisfactory-to-excellent yields, and no other byproducts besides water were produced in the reaction. The zebrafish model has become an important vertebrate model for evaluating drug effects. We tested the activity of 3n in zebrafish. The test results showed that 1 μg mL-13n treatments resulted in morphological malformation, and 0.01-0.1 μg mL-13n treatments led to potent angiogenic defects in zebrafish embryos. The results of this study will be of great significance for promoting drug research in cardiovascular and cerebrovascular diseases.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Different strategies for [4 + 2] cycloaddition of N-alkyl anilines and alkenes or alkynes by transition-metal catalysis.
Scheme 2
Scheme 2. Proposed strategy.
Scheme 3
Scheme 3. Reaction conditions: substrate 1 (0.2 mmol), aryl olefin (0.4 mmol), Fe(OTf)3 (10 μmol), AcOH (0.3 mmol), toluene (1.0 mL), at 140 °C under air for 24 h, and isolated yields of the products.
Scheme 4
Scheme 4. Reaction conditions: substrate 1 (0.2 mmol), aryl alkyne (0.4 mmol), Fe(OTf)3 (10 μmol), AcOH (0.3 mmol), toluene (1.0 mL), at 140 °C under air for 24 h, and isolated yields of the products.
Scheme 5
Scheme 5. Gram-scale synthesis and the drug effect of 3n treatment on vascular in the trunk of Tg(kdrl:EGFP) zebrafish embryos at 48 hpf. (A–D) control group and 1, 0.1, 0.01 μg mL−13n treated groups. Scale bar, 75 μm.
Scheme 6
Scheme 6. Mechanistic experiments.
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