Abstract

Palladium-catalyzed reactions of various haloanilines with 1,1-dimethylallyl alcohol were carried out in the presence of a hydrophilic ligand, 3,3′,3′′-phosphinidyne tris(benzenesulfonic acid) trisodium salt (TPPTS), or a lipophilic phosphine ligand, 1,1′-bis(diphenylphosphino)ferrocene (DPPF). The reactions proceeded chemoselectively in aqueous solvent to give C-vinylated products under basic conditions or N-allylated products under neutral conditions in practical yields (up to 79 %). The use of an aqueous solvent played an important role in this chemoselectivity and allowed the development of a one-pot synthesis of 3-methylindole. This chemoselectivity is synthetically useful because the reactive position of haloanilines can be controlled simply by changing the basicity of the reaction medium, which eliminates the need to protect the amino group during the reaction.

A three-step synthesis of a mixture of optically active cis- and trans-clavicipitic acids 6, which are ergot alkaloids, was achieved, starting from 4-bromoindole (7) and dl-serine (dl-2). This short synthesis was made possible by omitting the protection and deprotection steps from the synthetic route. The key step was the spontaneous cyclization of 4-vinyltryptophan (10) formed from the Heck reaction of 4-bromotryptophan (8) with 2-methyl-3-buten-2-ol (9) in aqueous media. During this investigation, we also found that the palladium-catalyzed reaction of 8 with 9 showed an interesting pH dependence; under strongly basic conditions, the Heck reaction occurred to give a C⁴-vinylated product 10, whereas an N-allylated product 19b was formed under neutral or weakly basic conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)