Enantioselective butenolide preparation for straightforward asymmetric syntheses of γ-lactones -: Paraconic acids, avenaciolide, and hydroxylated eleutherol

The naturally occurring gamma-lactones (+)-methylenolactocin (13) and its enantiomer, (+)-protolichesterinic acid (14) and its enantiomer, (+)-rocellaric acid (15), and the methylene bis(gamma-lactone) (-)-avenaciohde (16) were synthesized with 95-98% ees in very few steps. Enantiocontrol was imposed by the asymmetric dihydroxylation of trans-configured beta,gamma-unsaturated carboxylic esters (namely compounds 1i, 1j, and 1n) with AD mix-alpha (R) [for the levorotatory target structures, except for (-)-avenaciolide] or AD mix-beta (R) [for the dextrorotatory target structures plus (-)-avenaciolide]. beta,gamma-Unsaturated carboxylic ester le required increased amounts of the oxidant and auxiliary to produce the hydroxy lactone R,R-3e, a precursor of the naphtho-gamma-lactone (+)-9-hydroxyeleutherol (12; 96 % ee).