In connection with studies on the total synthesis of the aglycone of erythromycin B, erythronolide B (II), it was of interest to devise a method for the conversion of the cu,@-unsaturated ketone I to II. The ketone I is an especially attractive synthetic intermediate for several reasons including accessibility from an acyclic precursor.
1 Alkaline peroxidation of I can be expected to form stereospeclfically the 10, llfloriented epoxide' placing the substituents at C-11 in the required stereo-arrangement. It would only remain tc replace the C-10 oxygen substituent by methyl with retention of configuration and to cleave the acetonide grouping by the known procedure' to complete the synthesis of II. Because the introduction of the required methyl group is not feasible using conventional methods, a new approach was sought.
An attractive possibility for accomplishing the needed conversion is outlined in Scheme 1 which utilizes the oxime (A) corresponding to an cy,p-epoxy ketone. Reaction of this ketoxime with dimethylcuprate (Gilman) reagent was expected a priori to proceed via the deprotonated oxime (B) to the cu,punsaturated nitroso system (C) and thence by conjugate addition of methyl Gilman reagent to the dianion