Préparation des α-méthylène butyrolactones par réaction de Réformatsky; synthèse de l'acide protolichéstérinique

Abstract

Treatment of both tiglic (1) and angelic ester (2) with NBS resulted in a 2:1 mixture of γ-bromo-(3) and β'-bromo-tiglic ester (4). When Reformatsky conditions were applied to the latter (4) and cyclohexanone the product was primarily an α-methylene-butyrolactone derivative 5, with the characteristic spectral properties and reactivity of the exocyclic conjugated double bond. A six-membered cyclic transition state is proposed for this new type of reaction.
Similarly, both citraconic (9) and mesaconic ester (10) were brominated to β'-bromo-mesaconic ester (11). With myristic aldehyde (12) and zinc, this ester (11) afforded a 1:1 mixture of the trans- (13a) and cis-isomer (13b) of protolichesterinic ester. The NMR-signals could be assigned and confirmed the trans-configuration of the natural product (8). Attempts to saponify the ester mixture (13a and b) or to separate these isomers produced only lichesterinic ester (14) by migration of the double bond into the ring.
Finally citraconic anhydride (15) was brominated and the β'-bromo-citraconic anhydride (16) subjected to the Reformatsky conditions. The isolated product was trans-protolichesterinic acid (8), the racemic form of the natural product. The high stereospecificity can be explained by steric interactions in the above mentioned six-membered transition state.