美国加州大学尔湾分校Christopher D. Vanderwal课题组近日在氧化松香烷二萜的简易合成中取得新进展。2021年2月8日出版的《美国化学会杂志》发表了这项成果。

自由基多环化反应是受生物中阳离子环化反应启发的一种重要变种，其引发策略范围广，且自由基反应的官能团耐受性较好。在本文中，课题组人员证明Co催化MHAT引发的自由基双环化反应不仅可以兼容底物中几乎所有位点的氧化（通常是以去保护的形式），而且这些官能团还可以在这些提高复杂性的反应中导致高水平的立体化学控制。

具体来说，研究人员展示了六个不同位置上受保护或未保护羟基的作用及其对立体选择性的影响。此外，研究人员还展示了在这些反应中多重氧化的底物是如何反应的，并记录了这些反应在三种芳香族松香烷二萜的合成中的效用。

据悉，阳离子引发的多烯环化反应对于合成多环萜类化合物的作用是非常巨大的。然而，该反应的一个主要的局限性是很多相关的反应条件不能兼容底物极性的官能团，尤其是当这些官能团未受保护时。

附：英文原文

Title: Stereocontrolled Radical Bicyclizations of Oxygenated Precursors Enable Short Syntheses of Oxidized Abietane Diterpenoids

Author: Darius Vrubliauskas, Benjamin M. Gross, Christopher D. Vanderwal

Issue&Volume: February 8, 2021

Abstract: The power of cation-initiated cyclizations of polyenes for the synthesis of polycyclic terpenoids cannot be overstated. However, a major limitation is the intolerance of many relevant reaction conditions toward the inclusion in the substrate of polar functionality, particularly in unprotected form. Radical polycyclizations are important alternatives to bioinspired cationic variants, in part owing to the range of possible initiation strategies, and in part for the functional group tolerance of radical reactions. In this article, we demonstrate that Co-catalyzed MHAT-initiated radical bicyclizations are not only tolerant of oxidation at virtually every position in the substrate, oftentimes in unprotected form, but these functional groups can also contribute to high levels of stereochemical control in these complexity-generating transformations. Specifically, we show the effects of protected or unprotected hydroxy groups at six different positions and their impact on stereoselectivity. Further, we show how multiply oxidized substrates perform in these reactions, and finally, we document the utility of these reactions in the synthesis of three aromatic abietane diterpenoids.

DOI: 10.1021/jacs.0c13300

Source: https://pubs.acs.org/doi/10.1021/jacs.0c13300