Dibenzocycloheptanones construction through a removable P-centered radical: synthesis of allocolchicine analogues
Yan Zhang1, Zhenzhi Cai1, Julia Struwe2
1Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Drug Discovery & Innovation Center, College of Chemistry and Life Sciences, Zhejiang Normal University China zhangyan001@zjnu.edu.cn.
Abstract:
Dibenzocycloheptanones containing a tricyclic 6-7-6-system are present in numerous biologically active natural molecules. However, the simple and efficient preparation of derivatives containing a dibenzocycloheptanone scaffold remains difficult to date. Herein, we report a versatile strategy for the construction of these challenging seven-membered rings using a 7-endo-trig cyclization which is initiated by a phosphorus-centered radical. This approach provides a step-economical regime for the facile assembly of a wide range of phosphorylated dibenzocycloheptanones. Remarkably, we also have devised a traceless addition/exchange strategy for the preparation of dephosphorylated products at room temperature with excellent yields. Therefore, this protocol allows for the concise synthesis of biorelevant allocochicine derivatives.
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