1,2-dioxines as masked cis gamma-hydroxy enones and their versatility in the synthesis of highly substituted gamma-lactones.
Addition of highly stabilized ester nucleophiles to 1,2-dioxines affords good to high yields of gamma-lactones with high diastereoselectivity. Heterolytic or homolytic cleavage of the 1,2-dioxines under appropriate conditions generates the key reactive cis gamma-hydroxy enones, which ultimately afford the observed gamma-lactones. Diastereoselectivity is installed as a result of anti 1,4-addition by the ester enolate to the cis enones followed by intramolecular cyclization. The reaction is tolerant of a range of substitution patterns on the 1,2-dioxine while a broad range of esters are also accommodated. In addition to the synthesis of racemic gamma-lactones, highly enantioenriched gamma-lactones can also be synthesized when chiral cobalt(II) catalysts are employed for the initial homolytic ring-opening of the 1,2-dioxine.
Department of Chemistry, University of Adelaide, S.A., Australia, 5005, School of Chemistry, Monash University, Vic., Australia, 3800.
Ben W
BW
Greatrex
Marc C
MC
Kimber
Dennis K
DK
Taylor
Gary
G
Fallon
Edward R T
ER
Tiekink