Enantioselective Synthesis of Spirobilactams by Pd-Catalyzed N-Arylation

Significance

Reported here is the enantioselective synthesis of spirobi(3,4-dihydro-2-quinolone) derivatives 2 from malonamides 1 using a palladium-catalyzed intramolecular double N-arylation. The use of Pd(OAc)₂/(S)-BINAP as a catalytic system and K₃PO₄ as a base in N,N′-dimethylpropylene urea (DMPU) afforded the C ₂-symmetric spirobilactams 2 in high yields in most of the cases. The enantioselectivity is a function of the nature of R^² (5-70% ee) and is completely inhibited when R^² = 3,4-benzo. The authors suggested the generally accepted catalytic cycle, based on the Buchwald-Hartwig reaction (J. F. Hartwig and co-workers J. Am. Chem. Soc. 2006, 128, 9044; S. L. Buchwald and co-workers J. Am. Chem. Soc. 2007, 129, 13001) without evidence.