Nature has evolved exquisite synthetic pathways for terpenes by combining isoprenes into chains, folding them into carbocycles and then oxidizing and/or rearranging them into a vast range of complex molecules (>50,000 examples). Although laboratory syntheses can sometimes emulate elements of this process, additional approaches that can similarly emulate nature’s approach and lead to molecular diversity are desirable. Here we show that the synthesis of polycyclic terpene molecules can be achieved through a predictable and reliable process that starts from phenols. The synthetic route comprises three steps: prenylation, dearomatization and/or prenyl migration, and, finally, epoxidation and/or radical cyclization. Critically, the third step uses a cooperative bimetallic catalyst to mediate the cyclization of epoxy enones under hydrogenative conditions. Overall, this approach leads to the stereocontrolled formation of bicyclic-, linear-, angular-, clovane- and propellane-based terpene structures with functional groups that allow further manipulation. For example, these motifs can be repurposed for ring contractions to access additional terpene-based architectures. Of note, several natural products were prepared through a formal total synthesis using this approach; these routes are as concise as, and often shorter than, previously reported syntheses.

通过将异戊二烯组合成链，将它们折叠成碳环，然后将它们氧化和/或重新排列成范围广泛的复杂分子（>50,000 个示例），自然界已经进化出精巧的萜烯合成途径。虽然实验室合成有时可以模拟这一过程的元素，但可以类似地模拟自然方法并导致分子多样性的其他方法是可取的。在这里，我们展示了多环萜烯分子的合成可以通过从酚类开始的可预测且可靠的过程来实现。合成路线包括三个步骤：异戊二烯化、脱芳构化和/或异戊二烯迁移，最后是环氧化和/或自由基环化。至关重要的是，第三步使用协同双金属催化剂在加氢条件下介导环氧烯酮的环化。总体而言，这种方法导致双环、线性、角、氯烷和丙烷基萜烯结构的立体控制形成，这些萜烯结构具有允许进一步操作的官能团。例如，这些基序可以重新用于环收缩，以访问其他基于萜烯的架构。值得注意的是，使用这种方法通过正式的全合成制备了几种天然产物。这些路线与先前报道的合成一样简​​洁，而且通常更短。这些基序可以重新用于环收缩以访问其他基于萜烯的架构。值得注意的是，使用这种方法通过正式的全合成制备了几种天然产物。这些路线与先前报道的合成一样简​​洁，而且通常更短。这些基序可以重新用于环收缩以访问其他基于萜烯的架构。值得注意的是，使用这种方法通过正式的全合成制备了几种天然产物。这些路线与先前报道的合成一样简​​洁，而且通常更短。