Gianluigi Broggini

Intramolecular Pd(II)-catalyzed cyclization of propargylamides: straightforward synthesis of 5-oxazolecarbaldehydes.

Direct synthesis of 2-substituted 5-oxazolecarbaldehydes was performed by intramolecular reaction of propargylamides through treatment with a catalytic amount of Pd(II) salts in the presence of a stoichiometric amount of reoxidant agent. The heterocyclization process was well-tolerated by a wide range of aryl, heteroaryl, and alkyl propargylamides. This protocol constitutes a valuable synthetic pathway to 5-oxazolecarbaldehydes, alternative to the formylation on oxazole rings, often unsatisfactory in term of regioselectivity and yields.

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

Summary This review highlights the development of palladium-catalyzed C–H and N–H functionalization reactions involving indole derivatives. These procedures require unactivated starting materials and are respectful of the basic principle of sustainable chemistry tied to atom economy.

Tunable Pd-Catalyzed Cyclization of Indole-2-carboxylic Acid Allenamides: Carboamination vs Microwave-Assisted Hydroamination

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.

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

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.

Palladium-Catalyzed Domino Carbopalladation/5-exo-Allylic Amination of α-Amino Allenamides: An Efficient Entry to Enantiopure Imidazolidinones

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.

Uncommon intramolecular palladium-catalyzed cyclization of indole derivatives

Abstract A novel synthetic strategy based on the intramolecular palladium-catalyzed oxidative cyclization reaction, allows the formation of C–C bond and the synthesis of β-carbolinones. The reaction has been performed in the presence of catalytic amount of PdCl 2 (CH 3 CN) 2 and benzoquinone as a reoxidant.

Intramolecular Heck reaction of 2- and 3-iodoindole derivatives for the synthesis of β- and γ-carbolinones

A new synthesis of β- and γ-carbolinone derivatives was achieved by an intramolecular Heck cyclisation from the corresponding 3-iodo-1H-indole-2-carboxylic acid allyl-amides 8 and 2-iodo-1H-indole-3-carboxylic acid allyl-amides 9.

A facile synthesis of flumazenil analogues

Abstract A number of 8-substituted 5-methyl[1,2,3]triazolo[1,5-a][1,4] benzodiazepin-6(4H)-ones (6) were synthesised in a concise and efficient way starting from isatoic anhydrides and exploiting an intramolecular azide cycloaddition.

1,3-Dipolar cycloadditions to nitrogen-substituted allenes

A series of nitrogen-substituted allenes(2a–h) was treated with 3,5-dichloro-2,4,6-trimethylbenzonitrile oxide (4) in boiling tetrachloromethane. The reaction occurred predominantly (or exclusively) at the α,β double bond. Regardless of the site of cycloaddition, the carbon of the nitrile oxide bonded selectively to the central carbon of the allene. 4-Methylene-4,5-dihydroisoxazole monoadducts (5) reacted further to form spiro-diadducts. The stereochemistry of one diadduct was determined by X-ray diffraction analysis.

Synthesis of enantiopure 3-hydroxymethylchromanes via intramolecular nitrone cycloaddition

Abstract Enantiopure ( R ) and ( S ) 3-hydroxymethylchromanes were prepared by the intramolecular nitrone cycloaddition strategy, starting from allyl-type ethers of 2-hydroxybenzaldehydes and using ( R )- N -( α -phenylethyl)hydroxylamine as chiral auxiliary.