转自：康龙化成
Electrochemical Azo-free Mitsunobu-typeReaction
Quanping Guo,Yangye Jiang, Rongjin Zhu, Wenhui Yang, Pengfei Hu*
KeyLaboratory of Precise Synthesis of Functional Molecules of Zhejiang Province,Department of Chemistry, School of Science and Research Center for Industriesof the Future Westlake University 600 Dunyu Road, Hangzhou, 310030, ZhejiangProvince, China
—Angew.Chem. Int. Ed., 2024, DOI:10.1002/anie.202402878.
Recommended by Shi Li_ MOC
ABSTRACT:Theclassic chemical Mitsunobu reaction suffers from the need of excess alcoholactivation reagents and the generation of significant by-products. Efforts toovercome these limitations have resulted in numerous creative solutions, butthe substrate scope of these catalytic processes remains limited. Here wereport an electrochemical Mitsunobu-type reaction, which features azo-freealcohol activation and broad substrate scope. This user-friendly technologyallows a vast collection of heterocycles as the nucleophile, which can couplewith a series of chiral cyclic and acyclic alcohols in moderate to high yieldsand excellent ee’s.This practical reaction is scalable, chemoselective,uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air andmoisture. The synthetic utility is further demonstrated on the structuralmodification of diverse bioactive natural products and pharmaceuticalderivatives and its straightforward application in a multiple-step synthesis ofa drug candidate.
Background and idea of this work
Ligand screening
Condition optimization
Proposed mechanism
Synthesis of a VPS34 inhibitor
Pengfei Hu etal. developed a diazo-free electrochemical Mitsunobu-typereaction featuring the use of an electronrich triaryl phosphine and a halide-freeelectrolyte. Besides therecoverable phosphine oxide, hydrogengas appears to be the only side-product.Thesimple undivided cell setup, the use of commercially available inexpensiveelectrodes,together with the scalability, highlight the practicability of this reaction.Compared with other efforts towards sustainable Mitsunobu reaction, thisreaction has significantly broadscope,which can be readily used to modify and synthesize diverse bioactiveheterocyclic natural products and drug molecules derivatives.
