Development of a Protocol for Eight- and Nine-Membered Ring Synthesis in the Annulation of sp2,sp3-Hybridized Organic Dihalides with Keto Esters

A protocol has been developed in which annulation reactions of various dihalides with keto esters can be carried out to provide entry to eight- and nine-membered carbocycles. In this process wherein one alkenyl- or aryl bromide and a tethered alkyl chloride comprise the organic dihalide, a selective metal-halogen exchange reaction between the sp(2)-hybridized bromide and an organolithium initiates the process. Transmetalation to an organoytterbium reagent generates a species that undergoes selective carbonyl addition to the ketone of the keto ester, creating a lactone intermediate. Subjection of the resulting chloroalkyl lactone to intramolecular reductive coupling with samarium(II) iodide completes the desired annulation.