Sequential Diimination, Staudinger [2 + 2] Ketene-Imine Cycloaddition, and Ring-Closing Metathesis (RCM) Reactions: In Route to Bis(4-spiro-fused-ß-lactams)-Based Macrocycles.

Based on sequential organic transformations, that is, diimine formation, Staudinger [2 + 2] ketene-imine cycloaddition, and ring-closing metathesis (RCM) reactions, the synthesis with full structural identification including NMR and HRMS spectral data along with single X-ray diffraction analysis (for anti 7b, anti 8b, syn 9a, and anti 9b) of the first syn/anti bis-4-spiro-ß-lactams-based azacrown ethers (7a,b-9a,b) is reported.

Highly efficient Ru(ii)-alkylidene based Hoveyda-Grubbs catalysts for ring-closing metathesis reactions.

Three novel phosphine-free Ru-alkylidenes (7a-7c) have been synthesized and utilized as efficient catalysts for ring closing metathesis (RCM) reaction. Spectroscopic data, i.e. NMR and HRMS, along with single crystal X-ray diffraction analysis, were used to confirm their chemical structures. The tosylated carbenoid 7b showed the highest efficiency in cyclizing different acyclic diene substrates. RCM of various (un)substituted N,N-diallylaniline derivatives and stereoselective RCM of different macromolecular dienes were well tolerated using only a catalytic amount (0.5-2.0 mol%) of the additive catalyst (7b) as compared to the well-known Grubbs (II) and Hoveyda-Grubbs (II) catalysts.

Photochemistry of 1,4-Dihydropyridine Derivatives: Diradical Formation, Delocalization and Trapping as a Route to Novel Tricyclic and Tetracyclic Nitrogen Heterocyclic Ring Systems.

Irradiation of an acetonitrile solution of 4-aryl-3,5-dibenzoyl-1,4-dihydropyridine derivatives 1a-c and maleimides 2a-c using medium pressure Hg-arc lamp (λ > 290) nm afforded three different cycloadducts 4, 5, 6 in addition to the oxidation products 3. These results indicate that compounds 1a-c undergoes intermolecular cycloaddition reaction through three biradical intermediates and behave photochemically different than those reported previously for the analogous 3,5-diacetyl and 3,5-dicarboxylic acid derivatives. The present work also offers simple access to novel tricyclic and tetracyclic nitrogen heterocyclic ring systems of potential biological and synthetic applications. The structure of the photoproducts was established spectroscopically and by single crystal X-ray crystallography.

Photochemistry of benzotriazoles: generation of 1,3-diradicals and intermolecular cycloaddition as a new route toward indoles and dihydropyrrolo[3,4-b]indoles.

Irradiation of benzotriazoles 1a-e at λ = 254 nm in acetonitrile solution generated the corresponding 1,3-diradicals which underwent intermolecular cycloaddition with maleimides to afford the corresponding dihydropyrrolo[3,4-b]indoles and with acetylene derivatives to afford indoles as the major products. This offers an interesting and simple access to such ring systems of potential synthetic and biological interest. The structures of the photoproducts were established spectroscopically and by single crystal X-ray crystallography.

Unexpected behavior of enaminones: interesting new routes to 1,6-naphthyridines, 2-oxopyrrolidines and pyrano[4,3,2-de][1,6]naphthyridines.

Reaction of enaminones 1a-d with 2-aminoprop-1-ene-1,1,3-tricarbonitrile (2) in the presence of AcOH/NH4OAc afforded 7-amino-5-oxo-5,6-dihydro-1,6-naphthyridine-8-carbonitrile derivatives 9a-d. On the other hand, 2-aminopyrano[4,3,2-de] [1,6]naphthyridine-3-carbonitriles 20a-c,e were the only obtained products from the reactions of 1a-d with 2 in the presence of AcOH/NaOAc, while 1d afforded [3,5-bis-(4-chloro-benzoyl)-phenyl]-(4-chloro-phenyl)-methanone 21 under the same condition. The reaction of 2 with diethyl acetylenedicarboxylate in the presence of AcOH/NH4OAc afforded (4-cyano-5-dicyanomethylene-2-oxo-2,5-dihydro-1H-pyrrol-3-yl)-acetic acid ethyl ester 15B.

Enaminones in a multicomponent synthesis of 4-aryldihydropyridines for potential applications in photoinduced intramolecular electron-transfer systems.

An efficient three component reaction with enaminones, primary amines and aldehydes resulted in easy access to 1,4-dihydropyridines with different substituents at the 1-, 3-, 4- and 5-positions. Microwaves improved the reaction yield, reducing also considerably the reaction time and the amount of solvent used. Chiral primary amines gave chiral 1-substituted-1,4-dihydropyridines. The 4-(1-naphthyl) and 4-(phenanthren-9-yl)dihydropyridine derivatives exhibited an interesting photoluminescence behavior, which suggests their potential application as suitable photoinduced intramolecular electron-transfer systems.

Sequential Staudinger ketene-imine cycloaddition, RCM approach to highly rigid macrocrocyclic bisazetidinones.

An efficient approach to highly rigid macrocyclic bisazetidinones with interesting structural feature was achieved via sequential Staudinger ketene-imine cycloaddition of o-allyloxyphenoxyketene and bis-arylidenediamines followed by RCM. The ketene-imine cycloaddition afforded the corresponding bis-o-allyloxyphenoxyazetidinones as the cis-cis diastereomers, exclusively obtained as a mixture of cis-syn-cis and cis-anti-cis. RCM of the latter using Grubbs' catalysts afforded good yields of the corresponding novel macrocyclic bisazetidinones. The cis-anti-cis bisazetidinones are readily identified by (1)H NMR using Eu(hfc)(3) chiral shift reagent. (1)H NMR indicated the high shielding effect of the aryl substituents on one of the ortho-H's of the condensed phenylene ring, and VT (1)H NMR indicates the highly restricted rotation of the aryl groups, thus offering a highly rigid system.

Gas-phase pyrolytic reaction of 4-aryl-3-buten-2-ols and allyl benzyl ethers: kinetic and mechanistic study.

Flash vacuum pyrolysis (FVP) of 4-aryl-3-buten-2-ols [ArCH=CH-CH(CH3)OH, where Ar is phenyl, p-MeO, p-Me, p-Cl, p-NO2] gave the corresponding buta-1,3-dien-1-ylbenzene (ArCH=CH-CH=CH2, where Ar is Ph, p-MeO, p-Me, p-Cl, p-NO2) and 7-X-1,2-dihydronaphthalene derivatives (where X is H, MeO); FVP of 1-aryl-3-benzyloxy1-1-butenes and benzyl cinnamyl ethers [ArCH=CHCH(X)OCH2Ph, where Ar is phenyl, p-MeO, p-Me, p-Cl, X is H, Me, Ph] gave the corresponding but-2-en-1-ylbenzene derivatives (ArCH2CH=CH-X, where X is H, Me, Ph) together with benzaldehyde. The proposed mechanism of these pyrolytic transformations was supported by kinetic and product analysis.

A direct synthetic approach to uracil anhydrothionucleoside derivatives.

Direct conversion of peracylated N(1)-(beta-D-glucopyranosyl)-2-thiouracil derivatives into the corresponding anhydrothionucleosides has been studied under various conditions including: gas-phase pyrolysis, heating without a solvent, and by heating in a solvent of high boiling point (DPE) in the presence of a base (DABCO) and reaction in a microwave reactor. Heating at 210-220 degrees C was found to give the best yield of a single isomer. The structures of the new anhydrothionucleosides were confirmed by NMR techniques.

Staudinger ketene-imine cycloaddition, RCM approach to macrocrocyclic bisazetidinones.

Application of Staudinger ketene-imine cycloaddition reaction to bis-o-allyloxyarylideneamines afforded the corresponding bisallyloxyazetidinones as the cis-cis diastereomers, exclusively obtained as a mixture of cis-syn-cis and cis-anti-cis. RCM of the latter using Grubbs' catalysts afforded the corresponding macrocyclic bisazetidinones in good yields. The cis-anti-cis bisazetidinones are readily identified by (1)H NMR using Eu(hfc)(3) chiral shift reagent.