ABSTRACT
A variety of 3-vinyl-substituted imidazo[1,5-a]indole derivatives were synthesized by intramolecular Pd-catalyzed cyclization of the title allenamides through either a domino carbopalladation/exo-cyclization process or a novel hydroamination reaction that proceeds smoothly under microwave irradiation. Both the observed pathways involve a π-allyl-palladium(II) complex arising from insertion of the allene group into a palladium(II) species, the latter being formed in situ by the intervention of an aryl iodide or of the N-H group. In both cases, the role of nucleophile is covered by the indole nitrogen.
Subject(s)
Amides/chemical synthesis , Indoles/chemistry , Microwaves , Palladium/chemistry , Amides/chemistry , Amination , Carboxylic Acids , Catalysis , Cyclization , Molecular Structure , StereoisomerismABSTRACT
The isolation of sigma-alkylpalladium Heck intermediates, possible when beta-hydride elimination is inhibited, is a rather rare event. Performing intramolecular Heck reactions on N-allyl-2-halobenzylamines in the presence of [Pd(PPh(3))(4)], we isolated and characterized a series of stable bridged palladacycles containing an iodine or bromine atom on the palladium atom. Indolyl substrates were also tested for isolation of the corresponding complexes. X-ray crystallographic analysis of one of the indolyl derivatives revealed the presence of a five-membered palladacycle with the metal center bearing a PPh(3) ligand and an iodine atom in a cis position with respect to the nitrogen atom. The stability of the sigma-alkylpalladium complexes is probably a consequence of the strong constraint resulting from the bridged junction that hampers the cisoid conformation essential for beta-hydride elimination. Subsequently, the thus obtained bridged five-membered palladacycles were proven to be effective precatalysts in Heck reactions as well as in cross-coupling processes such as Suzuki and Stille reactions.
ABSTRACT
Allenamides of alpha-amino acids were converted into enantiopure 2-vinylimidazolidin-4-ones by a carbopalladation/exo-cyclization process. The products were obtained in 2.5:1-5.5:1 dr, with 94-99% ee. The palladium-catalyzed carbonylative cyclization of the same substrates afforded enone structures. Starting from properly substituted allenamides, an intramolecular carbopalladation followed by intramolecular amination gave rise to tricyclic fused-ring imidazolidinones.