A highly enantioselective α-benzoyloxylation of malonic diester has been achieved by phase-transfer catalysis. The reaction of α-monosubstituted tert-butyl methyl malonate with benzoyl peroxide in the presence of aqueous KOH and N-(9-anthracenylmethyl)cinchoninium chloride afforded the corresponding α,α-disubstituted products in generally excellent chemical yields (up to 99% yield) with high enantioselectivities (up to 96% ee). In addition, the utility of this methodology was exhibited by the synthesis of a mineralocorticoid receptor antagonist.

An organocatalyzed α-hydroxymethylation of αmonoalkyl malonic diesters using 37% aqueous formaldehyde (formalin) as a one-carbon electrophilic unit to generate all-carbon substituted quaternary stereocenters has been developed. In the course of our exploration of catalytic methodologies, a metal-free cooperative catalytic approach with cinchonidine and squaramide co-catalysts was found to improve both reactivity and enantioselectivity in this trans-formation. Our organocatalytic method represents the first example of an enantioselective α-hydroxymethylation of a malonic diester. The enantioenriched α-hydroxymethyl products could be recrystallized with high recovery, yielding optically pure materials. Moreover, to demonstrate the utility of this methodology, the all-carbon substituted α-quaternary stereogenic malonate was converted to both (S)-and (R)-4,4disubstituted oxazolidin-2-ones without loss of optical purity.

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