Palladium-Catalyzed,Modular Synthesis of Highly Functionalized Indoles and Tryptophans by Direct Annulation of Substituted o-Haloanilines and Aldehydes

摘要

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 deg 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.