Conjugate addition of 1,3-dicarbonyl compounds to maleimides using bifunctional primary amine‒(thio)phosphoramide organocatalysts

Asymmetric Michael additions of 1,3-dicarbonyl compounds to N-substituted maleimides were carried out using primary amine-(thio)phosphoramide bifunctional chiral organocatalysts derived from optically pure C2-symmetric 1,2-diamines. The addition ethyl 2-fluoroacetoacetate the 1,2-diphenylethane-1,2-diamine thiophosphoramide catalyst afforded various succinimides substituted with fluorine bearing quaternary carbon in high yields, good diastereomeric ratios and excellent enantiomeric excesses. Alicyclic β-ketoesters provided diastereomerically adducts yields enantioselectivities, whereas 2,4-pentanedione products slightly lower bulkiness N-substituent maleimide ring influenced mostly conversions. was found also efficient β-nitrostyrenes. Unprecedentedly, during this work highly enantioselective catalyzed by a amine‒hydrogen-bond donor groups containing organocatalyst. These reactions occurred through enamine intermediate, as evidenced electrospray-ionization mass spectrometry NMR spectroscopy.