Convenient synthesis of chiral tryptophan derivatives using Negishi cross-coupling

A facile synthetic procedure for chiral tryptophan derivatives using Negishi cross-coupling reaction of serine-derived iodoalanine with 3-haloindole is described. The best result was obtained when the reaction of N-tosyl-3-bromoindole with N-Cbz-iodoalanine methyl ester was carried out by the combination of Pd2(dba)3 and sterically hindered ferrocenyl ligand Q-PHOS. This reaction condition not only gave the desired tryptophan derivative as high as 76% yield, but also suppressed the formation of undesired products, the dehalogenated indole and the homodimer of indole, which were difficult to separate. This reaction was extended to the synthesis of various tryptophan derivatives having substituents on the benzene ring. The characteristic of this reaction is the practical biomimetic synthesis of chiral tryptophan derivatives in one-step.