Assembly of fluorinated chromanones via enantioselective tandem reaction
Mengxue Lu1, Zongli Xiong1, Yuqiao Zhou2
1School of Pharmaceutical Sciences and Chongqing Key Laboratory of Natural Drug Research, Chongqing University, Chongqing 401331, P. R. China. wangz1114@cqu.edu.cn yixia@cqu.edu.cn.
Abstract:
The enantioselective synthesis of fluorinated tricyclic chromanones with multiple vicinal stereogenic centers has been realized for the first time, through the tandem reaction between 2-fluorinated 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes. In the presence of chiral amine, the organo-tandem reaction including catalytic Michael addition/cycloketalization/hemiacetalization and acylation sequence provided a wide range of fluorinated tricyclic chromanones with excellent outcomes (>30 examples, up to >99% ee and >19 : 1 d.r.). A plausible catalytic cycle and transition state are also provided for this tandem reaction to rationalize the observed sense of asymmetric induction.
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