Total Syntheses of Paraconic Acids and 1,10-seco-Guaianolides via a Barbier Allylation/Translactonization Cascade of 3-(Bromomethyl)-2(5H)-furanone

A palladium-catalyzed Barbier allylation/translactonization cascade reaction was established for the rapid construction of beta,gamma-disubstituted alpha-exo-methylene-gamma-butyrolactone, an important motif in sesquiterpenes. Dimethyl zinc played significant roles in both steps for the umpolung of pi-allylpalladium as a nucleophile and promoting a Lewis acid-mediated translactonization. This sequence showed a broad substrate scope and was further harnessed for the synthesis of two paraconic acids as well as the first protecting-group-free total synthesis of two 1,10-seco-guaianolides.

Automated summary

A palladium-catalyzed Barbier allylation/translactonization cascade reaction was developed for the rapid construction of a key motif in sesquiterpenes, showing a broad substrate scope and enabling the synthesis of two paraconic acids and two 1,10-seco-guaianolides in a protecting-group-free total synthesis approach.