A General Synthesis of 5,6-Dihydro-α-pyrones

Article abstract of DOI:10.1021/jo01295a002

Crotonate esters substituted at C-3 by alkyl, alkoxy, or dialkylamino groups are deprotonated and the resulting dienolates added to aldehydes and ketones.Kinetic reaction is at C-2 of the ester, leading to the isolation of 2-alkyl-3-hydroxy esters such as 3 and 4 if the reaction mixture is quenched at -70 deg C.However, retroaldolization occurs readily.If the initial reaction mixtures are allowed to warm to 15 deg C before workup, the isolated products are 5,6-dihydro-α-pyrones (such as 5), accompanied in some cases by the (E)-4-substituted crotonate (such as 6).The method has been applied to the synthesis of a series of retinoid lactones (5f,18,21a-c) which are of interest as potential antineoplastic agents.