Carbon radicals from allyl O-(trimethylsilyl)-alpha-bromo-alpha,alpha-difluoroacetal can cyclize onto the olefinic part regiospecifically to give gamma-lactols in good yield. The lactols are then converted to the corresponding alpha,alpha-difluoro-gamma-lactones. Systematic synthesis of multifluorinated-alpha,alpha-difluoro-gamma-lactones has thus been accomplished through intramolecular radical cyclization as a key reaction. Semiempirical MO calculation study suggested a unique nature of alpha,alpha-difluoroacetate in that complete delocalization of the electrons in the SOMO orbital of alpha,alpha-difluoroacetyl radical occurred; this caused unsuccessful cyclization. To apply the present radical reaction, the first synthesis of both enantiomers of difluoroeldanolide, analogues of the sex pheromone of the male African sugarcane borer, has been demonstrated. Electrophysiological tests revealed that the difluorinated analogues were as active as the natural eldanolide on the olfactory receptors.

Substitution of fluorine atoms on an organic molecule makes it possible to modify the molecular orbital and electron density of the surface without changing its molecular shape. Point‐fluorinated analogues of the sex pheromone of the male African sugarcane borer were synthesized in optically active forms and their pheromone activities were investigated using an EAG test. The EAG activity of these point‐fluorinated pheromone analogues indicates that the point of fluorination has a critical influence on the pheromone activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Reactions of substituted acetone derivatives with acrylic acid esters (>200 mol %) in the presence of t-BuOK (200 mol %) in t-BuOH-THF (1:1 by volume) turned out to proceed as a cascade process consisting of the first Michael addition, the second Michael addition, and the last Claisen reaction to afford 4,4-disubstituted cyclohexane-1,3-diones. Only more substituted enolates play the role of a Michael donor in this cascade process, and therefore the ketone took up two alkoxycarbonylethyl groups on the same carbon bearing more substituents. Such intermediates were followed by intramolecular Claisen reactions leading to cyclohexane-1,3-diones bearing quaternary stereogenic centers at C(4), which bears an alkoxycarbonylethyl group and the substituent of the starting acetone derivatives. Thus-obtained 4,4-disubstituted cyclohexane-1,3-diones were successfully employed for total syntheses of intricate alkaloids of biological interest such as (+)-aspidospermidine, (+/-)-galanthamine, (+/-)-lycoramine, and (+/-)-mesembrine, all featuring quaternary stereogenic centers. DFT calculations provided us with clear-cut explanations for the observed chemoselectivity of the cascade process involving ketone-based enolates under thermodynamically controlled conditions.

No abstract