Diastereoselective Electrochemical Carboxylation of Chiral α-Bromocarboxylic Acid Derivatives:  An Easy Access to Unsymmetrical Alkylmalonic Ester Derivatives^1,†

The diastereoselective electrochemical carboxylation of chiral N-(2-bromoacyl)oxazolidin-2-ones has been studied. This reaction was carried out by cathodic reduction of the C−Br bond, in the presence of carbon dioxide, followed by treatment with diazomethane. The yields and the diastereomeric ratio of the two epimeric alkylmalonic acid derivatives are strongly affected by various factors:  solvent-supporting electrolyte system, temperature, electrode material, electrolysis conditions, oxazolidinone moiety. The higher yields (88%) were obtained starting from N-(2-bromopropionyl)-4R-phenyloxazolidin-2-one 1a, but with poor diastereoselectivity (61:39). The two epimers were easily separated by flash chromatography. The best results were achieved using a different chiral auxiliary:  Oppolzer's camphor sultam. Starting from 1j a good yield in carboxylated product was obtained (80%) with excellent diastereoselectivity (98:2). These chiral alkylmalonic acid derivatives are valuable building blocks in the synthesis of molecules with biological activity and of chiral propane-1,3-diols derivatives.