Palladium-catalyzed, modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes.
One-pot synthesis of indoles by a palladium-catalyzed annulation of ortho-haloanilines and aldehydes has been developed. Coupling of ortho-iodoaniline with aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85 degrees C], whereas X-Phos is found to be the ligand of choice for coupling reactions involving ortho-chloroanilines/ortho-bromoanilines and aldehydes. A variety of ortho-haloanilines with different electronic properties are suitable substrates, and aldehydes including chiral ones participated in this reaction without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from L-glutamic acid, with ortho-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields.
Jia
Yanxing
Y
Institut de Chimie des Substances Naturelles, CNRS, 91198 Gif-sur-Yvette Cedex, France.
Zhu
Jieping
J
D000447:Aldehydes / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry; D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis*; D010165:Palladium / Q000737:chemistry; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D000447:Aldehydes; D000814:Aniline Compounds; D007211:Indoles; D010165:Palladium; D014364:Tryptophan