基于光催化自由基阴离子[4+2]环加成反应的天然产物Lucidumone、(−)-Jiadifenin和(−)-Majucin不对称全合成

[4+2]环加成反应是最有效的碳碳键成键反应之一，它往往要求参与反应的两个组分电性相匹配，而电性不匹配的环加成反应往往需要在比较苛刻的反应条件下进行。近年来，光催化通过将有机分子活化为自由基阳离子或自由基阴离子，为化学家们发展新颖高效的合成方法提供了一种强大的平台，也为发展温和条件下电性不匹配的[4+2]环加成反应提供了可能，然而，目前尚无光催化的电性不匹配的不对称[4+2]环加成反应报道。我们拟利用手性Lewis酸提供手性诱导环境，发展不对称的光催化模式，实现缺电性双烯体和缺电性亲双烯体之间的[4+2]环加成反应，高效构筑含有多个手性中心的六元环骨架，并在此基础上，探索将该反应方法应用于一些复杂天然产物分子如lucidumone、(−)-jiadifenin和(−)-majucin的不对称合成。本项目体现了方法学创新和天然产物全合成的有机结合。

[4+2] cycloaddition has proved to be one of the most effective carbon-carbon bond-forming reactions. Generally, two electronically matched components, typically electron-rich diene and electron-deficient dienophile, are required for the sake of reaction efficiency and synthetic utility, while electronically mismatched cycloaddition could hardly occur under thermal conditions. Recently, photoredox catalysis has provided a powerful platform for developing novel chemical transformations under remarkably mild reaction conditions. Thus, challenging carbon-carbon bond formations could be realized attributing to the unique activation mode of photoredox catalysis, usually featured with a highly reactive radical cation or radical anion mediated process. In fact, the radical cation or radical anion formed during the interaction between the photocatalyst and organic molecules via single-electron transfer process, could efficiently promote the electronically mismatched [4+2] cycloaddition reaction to occur at rates several orders of magnitude greater than that of the corresponding neutral species under thermal conditions. However, the stereo control of this photocatalytic [4+2] cycloaddition remains a challenging task owing to the highly reactive nature of radical species. To date, there is no literature report to address the asymmetric photocatalytic [4+2] cycloaddition for two electronically mismatched substrates. .In this project, we plan to develop an asymmetric radical anion [4+2] cycloaddition between an eletron-deficient diene and an electron-deficient dienophile, leveraging the well- precedented combination of photoredox catalysis and chiral Lewis acid catalysis. We anticipate that the chiral Lewis acid would provide a fine chiral induction atmosphere for the vital radical addition process through prior coordination with the electron-deficient dienophile. In this way, the multi-substituted six-membered ring skeleton would be achieved in a single step with good enantio-selectivity, which would be prospectively applied for other catalytic scaffolds and find wide applications in the facile synthesis of complex molecules. As another important issue of this project, we plan to accomplish the asymmetric synthesis of three bioactive natural products, including lucidumone, (−)-jiadifenin and (−)-majucin, based upon the asymmetric radical anion [4+2] cycloaddition methodology described above.