Highly functionalized five-membered bicyclic a-Hydroxy acids from synthetic equivalent of glycolic acids

Five-membered cyclic α-hydroxy acids (1-hydroxycycycloalkane-1-carboxylic acids) are important constituents in biologically active natural products and also important precursor molecules for the synthesis of pharmacologically active compounds. This paper presents stereo selective synthesis of polysubstituted five-membered bicyclic α-hydroxy acid derivatives from α, α, α-dialkylated 1,3-dixolan-4-one (9). The synthesis was initiated on the α-propagylation of 2-(tert-butyl)-5-(1-ethenylprop-2-enyl)-1, 3-dixololan-4-one (trans-8) via its enolate, followed by intramolecular Pauson-Khand cyclization. The reaction was stereo selective and afforded two isomers (10a and 10b) in 4:1 ratio out of four possible diastereoisomers of bicyclic α-hydroxy acid (bicyclic 1-hydroxycarboxylic acid) derivatives. This method opens a new avenue to prepare synthetically useful highly functionalized stereoselctive synthesis of five-membered bicyclic α-hydroxy acids using a convenient and very effective method.