Development of a protocol for eight- and nine-membered ring synthesis in the annulation of sp(2),sp(3)-hybridized organic dihalides with keto esters

A protocol has been developed in which annulation reactions of various diha lides with keto esters can be carried out to provide entry to eight-:and ni ne-membered carbocycles. In this process wherein one alkenyl- or aryl bromi de and a tethered alkyl chloride comprise the;organic dihalide, a selective metal-halogen exchange reaction between the sp(2)-hybridized bromide and a n organolithium initiates the process. Transmetalation to an organoytterbiu m 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 w ith samarium(II) iodide completes the desired annulation.