Intramolecular Diels-Alder reaction of functionalized trienes: synthesis of medium-ring lactones

A simple preparative procedure has been developed for trienic systems, starting from cyclic alpha,beta-unsaturated acetals derived from crotonaldehyde and (E)-pent-2-enal. The reaction is initiated by a regioselective metallation at the gamma site of the unsaturated system that immediately induces 1,4-eliminative ring fission, and stereoselectively affords hydroxy-functionalized E-1,3-dienes. The esterification of those hydroxy dienes with acryloyl chloride gives activated trienes, suitable for intramolecular Diels-Alder reaction that yields medium-ring lactones. This method is relatively versatile with respect to the length and the substitution of the tether between the diene and the dienophile. The presence of additional stereogenic centres in the tether induces interesting selectivities during the cycloaddition step that are reported and discussed.