Lu Zuolin, Zhang Qingchun, Ke Miaolin, Hu Sha, Xiao Xiao, Chen Fener
Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou 310014, P.R. China.
Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, Shanghai 200433, P.R. China.
J Org Chem. 2021 Jun 4;86(11):7625-7635. doi: 10.1021/acs.joc.1c00672. Epub 2021 May 15.
We have developed a methodology for the greatly efficient construction of significant 2,3-dihydrobenzofuran scaffolds bearing a quaternary carbon center at the C2 position by means of [4 + 1] annulation reactions between -quinone methides and α-aryl diazoacetates as C1 synthons through organocatalysis by readily accessible TfOH catalyst under mild and transition metal-free conditions. This metal-free protocol furnishes an operationally simple and swift process for the free assembly of diverse highly functionalized 2,3-dihydrobenzofurans and also features broad substrate scope, excellent functional group compatibility, and environmental friendliness. Mechanistic investigation suggested that the reaction undergoes a rapid cascade protonation/intermolecular Michael addition/intramolecular substitution process.
我们已经开发出一种方法，通过在温和且无过渡金属的条件下，利用易于获得的三氟甲磺酸（TfOH）催化剂进行有机催化，使对醌甲基化物与作为C1合成子的α-芳基重氮乙酸酯之间发生[4 + 1]环化反应，从而高效构建在C2位置带有季碳中心的重要2,3-二氢苯并呋喃骨架。这种无金属方案为各种高度官能化的2,3-二氢苯并呋喃的自由组装提供了一种操作简单且迅速的过程，并且具有广泛的底物范围、出色的官能团兼容性和环境友好性。机理研究表明，该反应经历了快速的级联质子化/分子间迈克尔加成/分子内取代过程。
