Acyl radical cyclizations in synthesis. Part 4. Tandem processes: the 7-endo/5-exo serial cyclization approach to enantiomerically pure bicyclo[5.3.0]decan-2-ones

Abstract

Two diastereoisomeric phenylselenoesters of 4,5-dihydroxyhept-6-enoic acid were prepared as their acetonide derivatives from the chiral pool. On treatment with tributyltin hydride and azoisobutyronitrile the erythro isomer cyclized to give meso-4,5-dihydroxycycloheptanone, as its acetonide, in moderate yield whereas under the same conditions the threo-isomer gave a much lower yield of the corresponding C₂-symmetric ketone. In the erythro-series an alkyl group at C-7 of the heptenoyl system was found to retard significantly the direct endo-mode cyclisation; however, the cycloheptanone could still be obtained by a rearrangement when the tin hydride concentration was kept to a minimum. A tandem 7-endo/5-exo cyclization system was then constructed and tested, resulting in the formation of all four possible diastereoisomeric bicyclo[5.3.0]decanones. Further model studies were conducted on the effect of alkyl and alkoxy substituents at C-5 of the heptenoyl radical system on the mode of cyclisation. Alkyl substituents exert a steric effect whilst alkoxy substituents also have a stereoelectronic effect.