Abstract：
Transition-metal-catalyzed [4+4] cycloaddition leading to cyclooctanoids has centered on dimerization between 1,3-diene-type substrates. Herein, we describe a [4σ+4π-1] and [4σ+4π] cycloaddition strategy to access 7/8-membered fused carbocycles through rhodium-catalyzed coupling between the 4σ-donor (benzocyclobutenones) and pendant diene (4π) motifs. The two pathways can be controlled by adjusting the solvated CO concentration. A broad range (>40 examples) of 5-6-7 and 5-6-8 polyfused carbocycles was obtained in good yields (up to 90 %). DFT calculations, kinetic monitoring and 13C-labeling experiments were carried out, suggesting a plausible mechanism. Notably, one 5-6-7 tricycle was found to be a very rare, potent, and selective ligand for the liver X receptor β (KD=0.64 μM), which is a potential therapeutic target for cholesterol-metabolism-related fatal diseases.
摘要：
导致环辛烷的过渡金属催化的[44]环加成一直集中在1,3-二烯类型底物之间的二聚上。这里,我们扩展了[4σ4π-1]和[4σ4π]环加成策略，以通过4σ供体（苯并环丁烯酮）和悬垂二烯（4π）基序之间的Rh催化偶联来访问7/8元稠合碳环。这两种途径可以通过调节溶剂化CO浓度来控制。以良好的产率(高达90%)获得宽范围(>40个实例)的5-6-7和5-6-8个多稠合碳环。密度泛函理论(DFT)计算,进行了动力学监测和13C标记实验，提出了一个合理的机制。值得注意的是,5-6-7三轮车2v被发现是非常罕见的，强力，和肝X受体β的选择性配体（KD=0.64μM），它是胆固醇代谢相关致命疾病的潜在治疗靶点。
