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

• DOI: 10.1021/acs.orglett.0c04165
• Publication Date: 2021-01-27T19:39:35Z
• Authors: Weilong Liu; Zhimei Yu; Nicolas Winssinger
• Keywords: construction; seco; sesquiterpene; Chemical Sciences not elsewhere classified; Allylation; synthesis; info:eu-repo/classification/ddc/540; Biophysics; furanone; Total Syntheses; Biochemistry; Microbiology; 01 natural sciences; Dimethyl zinc; Bromomethyl; Barbier; palladium-catalyzed; exo; Genetics; Molecular Biology; substrate scope; paraconic acids; α-; methylene -γ-butyrolactone; motif; sequence; umpolung; π- allylpalladium; 0104 chemical sciences; Lewis acid-mediated translactonization; Infectious Diseases; guaianolide; disubstituted; ddc:540; Cascade; Medicine; protecting-group-free; role; nucleophile

A palladium catalyzed Barbier allylation/translactonization cascade reaction was established for the rapid construction of β,γ-disubstituted α-exo-methylene-γ-butyrolactone, an important motif in sesquiterpenes. Dimethyl zinc played significant roles in both steps for umpolung of π-allylpalladium as a nucleophile and promoting a Lewis acid mediated translactonization. This sequence showed 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.