Gaetano Zecchi

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.

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.

A cycloadditive route to trifluoromethyl-substituted aminoalcohols

Abstract A synthetic approach to the title compounds is described, involving the 1,3-dipolar cycloaddition of nitrones to trifluoromethyl-substituted alkene derivatives, followed by reductive ring opening of the so obtained isoxazolidines.

Synthetic approach to imidazo[1,2-a]pyridine derivatives by the intramolecular nitrone cycloaddition methodology

N-Benzyl and (R)-N-(α-phenylethyl) nitrones derived from 1-allyl-2-imidazolecarbaldehyde underwent intramolecular cycloaddition to give predominantly bridged-ring products, namely 5,6,8,9-tetrahydro-6,9-methanoimidazo[2,1-d][1,2,5]oxadiazepine derivatives. Catalytic hydrogenation of the latter furnished both racemic and enantiopure 6,8-functionalised 5,6,7,8-tetrahydro-imidazo[1,2-a]pyridines.

Regiochemical aspects of intramolecular cycloadditions of nitrones derived from N-(2-alkenyl)-2-pyrrolecarbaldehydes. Competitive entries to pyrrolizidine and indolizidine derivatives

Abstract Intramolecular cycloadditions of unsaturated nitrones derived from a series of N-(2-alkenyl)-2-pyrrolecarbaldehydes (2) have been systematically studied. A pronounced substituent effect has been observed as far as the competitive formation of fused- and bridged-ring regioisomers are concerned. Further elaboration of the two kinds of cycloadducts has given pyrrolizidine and indolizidine derivatives, respectively.

The first case of asymmetric induction in intramolecular nitrile imine cycloadditions: synthesis of enantiopure 3-substituted 6-oxo-2,3,3a,5-tetrahydro-4-carbomethoxy-furo[3,4-c]pyrazoles

Abstract Intramolecular cycloaddition of homochiral nitrile imines 5 , generated in situ from base treatment of the corresponding hydrazonoyl chlorides 4 , involves diastereoselective formation of the title compounds in the enantiomerically pure form.

Stereoselective intramolecular cycloadditions of homochiral nitrile imines: synthesis of enantiomerically pure 3,3a-dihydro-pyrazolo[1,5-a][1,4]benzodiazepine-6(4H)-ones

Abstract Starting from the commercially available ( S )-1-phenylethylamine, we have synthesised the homochiral hydrazonoyl chlorides 4 . The intramolecular cycloaddition of the corresponding nitrile imines 5 gave the diastereoisomeric 3,3a-dihydro-pyrazolo[1,5- a ][1,4]benzodiazepine-6(4 H )-ones 6 and 7 in enantiopure form.

SYNTHESIS OF BIS-(3,5)PYRAZOLOPHANES BY SEQUENTIAL INTERMOLECULAR-INTRAMOLECULAR NITRILIMINE CYCLOADDITIONS

Abstract A series of bis-(3,5)pyrazolophanes of potential interest in supramolecular chemistry have been synthesized by exploiting sequential intermolecular-intramolecular cycloadditions of properly functionalised nitrilimines.