1102 Natural Sciences II, Department of Chemistry, University of California, Irvine, California 92697-2025, United States.
J Am Chem Soc. 2021 Feb 24;143(7):2944-2952. doi: 10.1021/jacs.0c13300. Epub 2021 Feb 8.
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.
阳离子引发的多烯环化反应在多环萜类化合物的合成中具有重要作用。然而，一个主要的限制是许多相关的反应条件对包括极性官能团的不兼容性，特别是在未保护的形式下。自由基环化反应是受生物启发的阳离子变体的重要替代方法，部分原因是可能的引发策略范围广泛，部分原因是自由基反应对官能团的耐受性。在本文中，我们证明 Co 催化的 MHAT 引发的自由基双环化不仅对底物中几乎每个位置的氧化具有耐受性，通常在未保护的形式下，而且这些官能团还可以在这些产生复杂性的转化中提供高水平的立体化学控制。具体来说，我们展示了六个不同位置的保护或未保护的羟基的影响及其对立体选择性的影响。此外，我们展示了多氧化底物在这些反应中的表现，最后，我们记录了这些反应在三种芳香枞烷二萜类化合物合成中的应用。
