σ‐Alkylpalladium Intermediates in Intramolecular Heck Reactions:Isolation and Catalytic Activity

Abstract

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.

Recent Advances in Palladium‐Catalyzed Cross‐Coupling Reactions at ppm to ppb Molar Catalyst Loadings

“…Foley and co‐workers synthesized an N,C‐bidentate carbene ligand that gave full conversion in the reaction of iodobenzene with butyl acrylate at a loading of 10 mol ppm . A third N,C‐bidentate carbene ligand synthesized by Broggini and co‐workers permitted a decrease in the catalyst loading to 10 mol ppm during an optimization study; however, once more the scope of the reaction was examined at catalyst loadings of 0.1‐1 mol%. The Xiao group described the use of an N,C,N‐tridentate carbene ligand in a Heck reaction; during their examination of the scope of the reaction of aryl iodides, the catalyst loading was decreased to 1 mol ppm, and this afforded 78% conversion.…”

“…The Stille reaction, for which four publications report a mol ppm catalyst loading, is the second most studied cross‐coupling reaction. The Broggini group reported that an N,C‐bidentate ligand formed a palladacycle that was sufficiently active to promote 7 Stille reactions at a catalyst loading of 100 mol ppm . The reaction was performed without a base in DMF at 80 °C for 24 hours, and 11 examples were presented.…”

A Tandem “On‐Palladium” Heck–Jeffery Amination Route Toward the Synthesis of Functionalized Indole‐2‐carboxylates

“…Further experiments (entries 4–9) allowed us to identify satisfactory conditions (entry 9). Several failed optimization attempts provided circumstantial evidence indicating the lack of involvement of a Pd 0 ‐species as the active catalyst, differing from a straightforward Heck reaction 7c. For example, the reaction failed completely when conducted in an ionic liquid solvent [entries 10 and 11, IL‐109 = trihexyl(tetradecyl)phosphonium bistriflimide], a media known to be highly effective in Pd 0 ‐mediated amination6b and Heck processes 6e.…”

Arylation of α‐Chiral Ketones by Palladium‐Catalyzed Cross‐Coupling Reactions of Tosylhydrazones with Aryl Halides

“…[13] Further experimentation revealed that the use of Pd(OAc) 2 instead of [Pd 2 (dba) 3 ] provided higher yields. For this reason, we carried out a study of the influence of different amounts of water, which revealed that the coupling reaction could be best accomplished in the presence of 5 equivalents of water.…”

“…Under these conditions, the allyl amine 17 a was obtained in an acceptable 65 % yield (Scheme 5). [13] Further experimentation revealed that the use of Pd(OAc) 2 instead of [Pd 2 (dba) 3 ] provided higher yields. Employing this methodology, a variety of chiral N-Bocprotected allyl amines 17 were prepared from tosylhydrazone 16 (Scheme 6).…”