Tzi‐Chi LiuZih‐Hao LinWoo-Jin Yoo2024-08-282024-08-282024-08-13https://scholars.lib.ntu.edu.tw/handle/123456789/720449An improved synthetic procedure for the intramolecular ketene [2+2] cycloaddition was developed for the preparation of 1-heteroatom-substituted bicyclo[2.1.1]hexan-5-ones. It was found that the use of the Mukaiyama reagent (2-chloro-N-methyl-pyridinium iodide) was key to efficiently generate the α-heteroatom substituted homoallyl ketene intermediate for the cycloaddition reaction. The synthetic utility of the resulting bicyclic ketone was demonstrated through the preparation of a saturated variant of vortioxetine.enCycloadditionIsosteresKeteneSynthetic Methods[SDGs]SDG3journal article10.1002/ajoc.202400302