Free radical initiated ring expansion of twelve-, thirteen-, and fourteen-membered carbocyclic rings is described together with a new synthesis of (R)-(-)-muscone.
Free radical-initiated ring expansion affords entry to medium-ring carbocycles and heterocycles otherwise difficultly obtained 1ZJ The method should also be applicable to the preparation of large rings with useful functional groups, thereby taking advantage of the ready availability of twelve-membered rings to reach larger, less accessible members of the series. As an exampie, tri-n-butyitin hydride treatment of the readiiy avaiiabie i~domethyic~yciododecimone fiketo ester 24 yielded (79%) the thirteen-membered y-keto ester 3 (eq l).sa Sequential two-carbon and_ one-carbon ring expansion of cyclododecanone 1 provides access
(2)
to fifteen-membered rings. Treatment of the morpholine enamme of cyclododecanone with methyl propiolate,6 followed by hydrogenation of the ring-expanded enone, yielded the fourteen-membered P-keto ester 4.sa Alkylation with methylene iodide followed by ring expansion using the tin hydride method (eq 2) then yielded the fifteen-membered yketo ester 5 (50%)."a In similar fashion, the six-