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

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.

多烯的阳离子引发环化在多环萜类化合物合成中的作用怎么强调都不为过。然而，一个主要的局限是许多相关反应条件无法容忍底物中包含极性官能团，特别是未受保护的形式。自由基多环化是仿生阳离子变体的重要替代方法，部分原因是可能的引发策略多样，部分是因为自由基反应对官能团的耐受性。在本文中，我们证明了钴催化的氢原子转移（MHAT）引发的自由基双环化不仅能容忍底物中几乎每个位置的氧化（通常是未受保护的形式），而且这些官能团还能在这些产生复杂性的转化中有助于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上受保护或未受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型松香烷二萜类化合物合成中的应用。