Department of Chemistry, Fudan University, 2005 Songhu Road, Shanghai, 200438, China.
Academy for Engineering and Technology, Fudan University, 2005 Songhu Road, Shanghai, 200438, China.
Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202202046. doi: 10.1002/anie.202202046. Epub 2022 Apr 5.
γ-Butenolide and γ-butyrolactone scaffolds are two types of important core structures in numerous natural products and bioactive targets. However, methods to construct the chiral quaternary arylated γ-butenolide are rarely explored. We herein report an efficient Pd-catalyzed enantioselective γ-arylation of β,γ-unsaturated butenolides with aryl bromides, which shows high γ-selectivity, good functional group tolerance and excellent enantioselectivity. Notably, this protocol also allows for facile construction of tricyclic tetrahydroindolines and tetrahydroisoquinolinones in one step. DFT calculations are consistent with the experimental results, suggesting that the γ-arylation is favoured over the α-arylation. Finally, this method is applied to the rapid synthesis of natural product (R)-(+)-boivinianin A.
γ-丁内酯和 γ-丁内酯骨架是许多天然产物和生物活性靶标中两种重要的核心结构。然而，构建手性季芳基γ-丁内酯的方法却很少被探索。我们在此报道了一种高效的 Pd 催化的 β,γ-不饱和丁烯内酯与芳基溴化物的对映选择性γ-芳基化反应，该反应具有高 γ-选择性、良好的官能团耐受性和优异的对映选择性。值得注意的是，该方案还可以一步法轻松构建三环四氢吲哚啉和四氢异喹啉酮。DFT 计算结果与实验结果一致，表明γ-芳基化反应优于α-芳基化反应。最后，该方法被应用于天然产物 (R)-(+)-boivinianin A 的快速合成。
