Diastereomeric Amides Derived from Malonic Acid: The Role of Chiral Auxiliaries and of the Nature of Co-Acids in the Mixed Kolbe Electrolyses

Abstract

Experiments towards the diastereoselective coupling of new malonic acid amides synthesized with commercially available chiral amines [(S)-(+)-1-cyclohexylethylamine and (R)-(+)-1-phenylethylamine] as chiral auxiliaries were performed through Kolbe oxidations [undivided cell, Pt (anode and cathode), MeOH, 5% to 10% KOH neutralisation, 200 to 250 mA/cm2], using different co-acids (hexanoic, trimethylsilylacetic and diethylphosphonoacetic acids and phthaloylglycine). New long chain and silylated amides (mixed Kolbe dimer) were obtained in good yields (56 to 63%) and low diastereoselectivity, in the presence of a large excess of co-acids, together with disproportionation and non-Kolbe (nK) products, mainly methoxy derivatives. Coupling was more effective with radicals with opposite reactivity. Electrophilic radicals couple between themselves to a lesser extent. Diastereoselective induction was not high. Studies performed with phthaloylglycine, under Kolbe conditions, in the absence and presence of hexanoic acid as a co-acid led to the symmetrical dimer, a N-methoxymethyl-hydroxylactam and a N-methoxyphthalimide. In the presence of hexanoic acid, the latter products were obtained together with alkylated imide and the corresponding hydroxylactam.