Development of enantioselective intramolecular N-arylation reactions for the desymmetrization of achiral dinitrogen malonamide derivatives

An effective methodology for the enantioselective intramolecular (Buchwald-Hartwig) amidation of prochiral dinitrogen malonamide derivatives has been developed in quantitative yield and good enantioselectivities. The best result was obtained based on an enantiopure (R)-MOP/Pd(OAc)₂ catalytst system with either Cs₂CO₃ or K₃PO₄ in refluxing THF affording the 4-methoxybenzyl substituted diamide derivative, 3-methyl-N, 1-bis(4-methoxbenzyl)-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxamide, in 99% yield and 75% enantiomeric excess. This example serves as a preliminary example of a desymmetrization of prochiral dinitrogen nucleophiles by preferential N-arylation. The intermolecular version of this reaction proved to be more challenging than its intramolecular counterpart and no coupling products were obtained. Other malonamide derivatives were prepared with a pendant bromovinyl substituent at the αposition and cyclized intramoleculary employing a mild Goldberg reaction to form 5-membered rings in good yield and unknown enantioselectivity.