Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States.
J Am Chem Soc. 2023 May 31;145(21):11622-11632. doi: 10.1021/jacs.3c01618. Epub 2023 May 2.
Asymmetric radical bicyclization processes have been developed via metalloradical catalysis (MRC) to stereoselectively construct chiral chromanones and chromanes bearing fused cyclopropanes. Through optimization of a versatile -symmetric chiral amidoporphyrin ligand platform, a Co(II)-metalloradical system can homolytically activate both diazomalonates and α-aryldiazomethanes containing different alkene functionalities under mild conditions for effective radical bicyclization, delivering cyclopropane-fused tricyclic chromanones and chromanes, respectively, in high yields with excellent control of both diastereoselectivities and enantioselectivities. Combined computational and experimental studies, including the electron paramagnetic resonance (EPR) detection and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) trapping of key radical intermediates, shed light on the working details of the underlying stepwise radical mechanisms of the Co(II)-catalyzed bicyclization processes. The two catalytic radical processes provide effective synthetic tools for stereoselective construction of valuable cyclopropane-fused chromanones and chromanes with newly generated contiguous stereogenic centers. As a specific demonstration of synthetic application, the Co(II)-catalyzed radical bicyclization has been employed as a key step for the first asymmetric total synthesis of the natural product (+)-Radulanin J.
不对称自由基双环化反应已通过金属自由基催化（MRC）得到发展，用于立体选择性构建手性色满酮和带有稠合环丙烷的色烷。通过对多功能 -对称手性酰胺卟啉配体平台进行优化，Co(II)-金属自由基体系可以在温和条件下均裂激活二烯丙基丙二酸盐和含有不同烯烃官能团的α-芳基重氮甲烷，用于有效自由基双环化，分别以高收率和优异的非对映选择性和对映选择性提供环丙烷稠合的三环色满酮和色烷。包括电子顺磁共振（EPR）检测和关键自由基中间体的 2,2,6,6-四甲基-1-哌啶氧基（TEMPO）捕获的组合计算和实验研究，阐明了 Co(II)催化双环化过程中分步自由基机制的工作细节。这两个催化自由基过程为立体选择性构建具有新生成连续立体中心的有价值的环丙烷稠合色满酮和色烷提供了有效的合成工具。作为合成应用的具体例证，Co(II)-催化的自由基双环化已被用作天然产物（+）-Radulanin J 的首次不对称全合成的关键步骤。
