To illustrate the synthetic significance of C-C activation methods, here we describe an efficient strategy for the enantioselective total syntheses of (-)-cycloclavine and (-)-5- epi-cycloclavine, which is enabled by an asymmetric Rh-catalyzed "cut-and-sew" transformation between benzocyclobutenones and olefins. Despite the compact structure of cycloclavine with five-fused rings, the total synthesis was accomplished in 10 steps with a 30% overall yield. Key features of the synthesis include (1) a Pd-catalyzed tandem C-N bond coupling/allylic alkylation sequence to construct the nitrogen-tethered benzocyclobutenone, (2) a highly enantioselective Rh-catalyzed carboacylation of alkenes to forge the indoline-fused tricyclic structure, and (3) a diastereoselective cyclopropanation for preparing the tetrasubstituted cyclopropane ring. Notably, an improved catalytic condition has been developed for the nitrogen-tethered cut-and-sew transformation, which uses a low catalyst loading and allows for a broad substrate scope with high enantioselectivity (94-99% e.e.). The C-C activation-based strategy employed here is anticipated to have further implications for syntheses of other natural products that contain complex fused or bridged rings.

中文翻译：

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通过不对称 CC 激活简明合成 (-)-Cycloclavine 和 (-)-5-epi-Cycloclavine

为了说明 CC 活化方法的合成意义，我们在这里描述了一种有效的 (-)-环克拉霉素和 (-)-5- 表环克拉霉素的对映选择性全合成策略，该策略由不对称 Rh 催化的“切割-苯并环丁烯酮和烯烃之间的“缝”转化。尽管具有五个稠环的环克拉霉素结构紧凑，但全合成分 10 步完成，总产率为 30%。该合成的关键特征包括（1）Pd催化的串联CN键偶联/烯丙基烷基化序列以构建氮系苯并环丁烯酮，（2）高度对映选择性Rh催化的烯烃碳酰化以形成二氢吲哚稠合的三环结构， (3)用于制备四取代环丙烷环的非对映选择性环丙烷化反应。尤其，已经为氮系链切割和缝合转化开发了一种改进的催化条件，它使用低催化剂负载量并允许具有高对映选择性 (94-99% ee) 的广泛底物范围。预计此处采用的基于 CC 激活的策略将对包含复杂稠合或桥连环的其他天然产物的合成产生进一步的影响。