Diastereoselective Palladaelectro-Catalyzed Construction of Bromomethyl Morpholines as Key Step To Access Morpholino Homonucleosides.

A synthetic protocol for the preparation of a new class of morpholino homonucleosides in enantiopure form starting from readily available 1,2-aminoalcohols or glycidol has been developed. Key intermediates of the synthetic sequence are 2-bromomethyl morpholines, diastereoselectively achieved from the corresponding alkenols by palladaelectro-catalyzed alkoxybromination of unactivated alkenes. The so obtained bromo derivatives are in turn susceptible to functionalization with nucleic bases for easy access to morpholino homonucleosides.

Copper(II)-Catalyzed Three-Component Arylation/Hydroamination Cascade from Allyl Alcohol: Access to 1-Aryl-2-sulfonylamino-propanes.

A new straightforward approach to 1-aryl-2-aminopropanes using easily accessible substrates has been developed. Simple allyl alcohol is shown to be an ideal synthetic equivalent of the C3 propane-1,2-diylium bis-cation synthon in three-component cascade reactions with arenes and sulfonamide nucleophiles to regioselectively afford 1-aryl-2-aminopropanes. The reaction is catalyzed by Cu(OTf)2 and is expected to involve a Friedel-Crafts-type allylation of the arene, followed by hydroamination.

Phosphine-Catalyzed Domino Regio- and Stereo-Selective Hexamerization of 2-(Bromomethyl)acrylates to 1,2-Bis(cyclohexenyl)ethenyl Derivatives.

A phosphine-catalyzed domino assembly of six units of 2-bromomethyl acrylates afforded polyalkenyl adducts containing two cyclohexenyl rings. This reaction occurs under mild conditions providing the final product by formation of seven carbon-carbon bonds and four stereocenters. Experimental and computational studies support an initial dimerization of the substrate, which in turn trimerizes involving two totally regio- and stereocontrolled Diels-Alder cycloadditions. The yield of the hexamerization of the 2-bromomethyl acrylates depends on the size of the ester function. The protocol has also proved to be practicable on a gram scale.

Non-Decarboxylative Ruthenium-Catalyzed Rearrangement of 4-Alkylidene-isoxazol-5-ones to Pyrazole- and Isoxazole-4-carboxylic Acids.

Treatment of 4-(2-hydroaminoalkylidenyl)- and 4-(2-hydroxyalkylidenyl)-substituted isoxazol-5(4H)-ones with catalytic amounts of [RuCl2(p-cymene)]2, without any additive, afforded pyrazole- and isoxazole-4-carboxylic acids, respectively. The presence of an intramolecular H-bond in these substrates was the key to divert the classical mechanism toward a ring-opening non-decarboxylative path that is expected to generate a vinyl Ru-nitrenoid intermediate, the cyclization of which affords the rearranged products. A gram scale protocol demonstrated the synthetic applicability of this transformation.

Direct Synthesis of Fluorescent Oxazolo-phenoxazines by Copper-Catalyzed/Hypervalent Iodine(III)-Mediated Dimerization/Cyclization of 2-Benzylamino-phenols.

A dimerization/cyclization reaction of 2-benzylamino-phenols for the direct synthesis of the oxazolo-phenoxazine skeleton is reported. The reaction occurs under copper catalysis in the presence of hypervalent iodine(III), giving selectively the 5H-oxazolo[4,5-b]phenoxazine compounds. The cascade process, which allows the conversion of the substrates into the tetracyclic products, involves three C-H functionalization steps. Initial oxidation of electron-rich arenes by the hypervalent iodine is essential for the dimerization of substrates, whereas the formation of the five-membered rings is promoted by the copper species. 1-Benzyl-2-phenyl-6-(aryl-benzyl)amino-benzimidazoles are regioselectively obtained using N,N'-dibenzyl-phenylenediamines as starting substrates. The fluorescence emission properties of these classes of products have been evaluated.

Intramolecular Aminoazidation of Unactivated Terminal Alkenes by Palladium-Catalyzed Reactions with Hydrogen Peroxide as the Oxidant.

The palladium-catalyzed aminoazidation of aminoalkenes yielding azidomethyl-substituted nitrogen-containing heterocycles was developed. The procedure requires oxidative conditions and occurs at room temperature in the presence of hydrogen peroxide and NaN3 as the azide source. These conditions provide selective exo-cyclization/azidation of the carbon-carbon double bond, furnishing a versatile approach toward five-, six-, and seven-membered heterocyclic rings.