Synfacts 2009(6): 0602-0602  
DOI: 10.1055/s-0029-1216707
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

Enantioselective Synthesis of Spirobilactams by Pd-Catalyzed N-Arylation

Contributor(s): Victor Snieckus, Emilie David
K. Takenaka, N. Itoh, H. Sasai*
Osaka University, Japan
Further Information

Publication History

Publication Date:
25 May 2009 (online)


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 R² (5-70% ee) and is completely inhibited when R² = 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.