Intramolecular [2+2] Cycloadditions of α‐Heteroatom Substituted γ,δ‐Unsaturated Ketenes

An 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.