The desymmetrization of prochiral diesters with a chiral phosphoric acid catalyst to produce highly enantioenriched lactones in excellent yield is reported. The process is easily scaled and accommodates a variety of substitution patterns, many of which result in the generation of an enantioenriched all-carbon quaternary center. Manipulation of lactone product to useful small building blocks is also described.

An efficient synthesis of enantioenriched α-substituted γ-hydroxy esters via a kinetic resolution event is described. Bulky racemic esters in the presence of a chiral Brønsted acid selectively lactonize to yield a recoverable enantioenriched hydroxy ester and lactone. These esters are highly versatile building blocks that can readily be converted to synthetically useful materials.

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The article describes highly efficient and generalized procedure for the synthesis of enantioenriched lactones containing a quaternary center through a Brønsted acid catalyzed desymmetrization of hydroxy diesters. The process has been improved to utilize only 1 mol% of Binol based phosphoric acid and proceed in under 48 hours.