Palladium-catalyzed, modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes

Article abstract of DOI:10.1021/jo061471s

(Chemical Equation Presented) 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°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 orthohaloanilines 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.