A DABCO-promoted bicyclization/rearrangement reaction has been developed for the synthesis of tetrasubstituted furans from 1,4-enediones at room temperature. This transformation involves aza-Michael addition, intramolecular bicyclization, and rearrangement processes. In addition, the 4-ureidofuran-3-carboxylate ester products can further be converted to furo[3,4-d]pyrimidine-2,4-diones through intramolecular substitution cyclization under heating conditions.
Category Archives: European Journal of Organic Chemistry
Photoinduced 1,3‐Dipolar Cycloadditions of Cyclic Enones and 2,5‐Disubstituted Tetrazoles: An Unprecedented Pathway to Polysubstituted Pyrazolines and Pyrazoles.
We report herein the syntheses of original pyrazolines and pyrazoles through 1,3-dipolar cycloaddition of cyclic enones with 2,5-disubstituted nitrile imines achieved via photochemical activation of 2,5-diaryl substituted tetrazoles. Monitoring of the reactions, similar to nitrile imine-mediated tetrazole-ene cycloadditions (NITEC), could be performed by means of UV-vis absorption and emission measurements. The presence or absence of substituents in the alpha position of the ketone function makes it possible to direct these reactions towards the selective formation of pyrazoles or pyrazolines. The choice of the cyclic enones and 2,5-disubstituted tetrazoles proved crucial for the fluorescence properties of the polycyclic derivatives obtained.
Use of Formic Acid as a CO Surrogate for the Reduction of Nitroarenes in the Presence of Dienes: A Two‐Step Synthesis of N‐Arylpyrroles via 1,2‐Oxazines
Formic acid was employed as a CO surrogate to deoxygenate nitroarenes to nitrosoarenes, a reaction catalyzed by a palladium/phenanthroline complex. Nitrosoarenes, trapped by conjugated dienes, afforded 3,6-dihydro-2H-[1,2]-oxazines. The latter were then transformed into N-arylpyrroles employing CuCl as the catalyst. The reaction allows to prepare pyrroles lacking any substituent in the 2 and 5 positions, which are difficult to produce employing most pyrrole syntheses.
Abstract
Formic acid, activated by acetic anhydride and a base, was employed as a CO surrogate to deoxygenate nitroarenes to nitrosoarenes, a reaction catalyzed by a palladium/phenanthroline complex in the homogeneous phase. Nitrosoarenes were trapped by conjugated dienes to give 3,6-dihydro-2H-[1,2]-oxazines. The latter were then transformed into N-arylpyrroles employing CuCl as the catalyst. The reaction was designed to give the best results for pyrroles lacking any substituent in the 2 and 5 positions, which are difficult to produce employing most pyrrole syntheses.
Solvent Directed Diastereodivergent Synthesis of Spiro‐Oxindoles with Quaternary Carbon Center Forming
An efficient method has been developed to achieve solvent-directed diastereodivergent cyclization reactions with quaternary center formation. A series of products were obtained with good yields and diastereoselectivities.
Abstract
An efficient method has been developed for the solvent-directed diastereodivergent cyclization reactions with quaternary center formation. Various spiro-oxindole diastereoisomers were synthesized with good yields (up to >99 %) and moderate to high diastereoselectivities (up to >20 : 1). Further study on NMR studies indicates that the key to this approach lies in different interactions between the substrate and organocatalyst across diverse solvents. This methodology may have significant implications for switchable, solvent-directed diastereodivergent synthesis.
Azodicarboxylate‐Mediated Peptide Cyclisation: Application to Disulfide Bond Formation in Solution and Solid Phase
Herein, the application of diethylazodicarboxylate as an efficient and highly chemoselective oxidising reagent for the cyclisation of peptides through a disulfide bond is demonstrated. The scope of this application was demonstrated both in solution and on solid phase, and can be extended to the cyclisation of peptides containing oxidation-sensitive residues, such as methionine and tryptophan.
Abstract
Cyclic peptides are important molecules, playing key roles in protein architecture, as chemical probes, and increasingly as crucial structural elements of clinically-useful therapeutics. Herein we report methodology using azodicarboxylates as efficient reagents for the facile synthesis of cyclic peptides through a disulfide bridge. The utility of this approach in both solution and solid-phase, and compatibility with common amino acid side chain functionalities is demonstrated, resulting in cyclic peptides in good yield and purity. This approach has significant potential application for synthesis of molecules of biological or therapeutic significance.
Pd‐Catalyzed [3+2]‐Dehydrogenative Annulation Reactions
Pd-catalyzed [3+2] annulations go dehydrogenative: a new protocol enables the Pd(II)-catalyzed [3+2] annulation between resonance-stabilized acetamides (or 3-oxoglutarates) and β,γ-unsaturated cyclic carbonyl derivatives. This dehydrogenative strategy represents a more atom- and step- economical version than the corresponding Pd(0)-catalyzed redox-neutral couplings previously studied by our group, enabling the straightforward construction of a number of heteropolycyclic structures.
Abstract
The significance of cross dehydrogenative couplings has increased considerably in recent years. This article revisits the [3+2] C−C/N−C, C−C/O−C and C−C/C−C annulation strategy, recently reported by our group, according to a Pd(II) catalyzed dehydrogenative variant. Our original report relied on Pd(0) catalysis, using α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles and resonance-stabilized acetamides or 3-oxoglutarates as C/N and O/C or C/C bis-nucleophiles, respectively. In this more modern and straightforward Pd(II)-catalyzed dehydrogenative approach, β,γ-unsaturated carbonyl derivatives replace α,β-unsaturated-γ-oxy carbonyls as bis-electrophiles. Our study includes experimental optimization and showcases the synthetic versatility in the formation of diverse heterocyclic structures, such as bicyclic lactams, furo-cycloalkanones and bicycloalkane-diones. Furthermore, a mechanism is proposed to elucidate the underlying processes involved in these reactions.
Trichloromethylative Olefin Lactonization by Photoredox Catalysis
Trichloromethylative olefin lactonization was reported. A photoredox iridium catalyst irradiated with blue LEDs promoted the reaction without using hazardous reagents. The mechanistic studies were performed by experimental and theoretical means. The trichloromethyl moiety of the product could be converted to the corresponding dichloroalkene and chloroalkyne in addition to the carboxyl group.
Abstract
A trichloromethylative olefin lactonization reaction using an iridium photoredox catalyst was developed. The reactions proceeded at room temperature for olefins with various substituents and substitution patterns, and a variety of lactones with a tetrasubstituted carbon and trichloromethyl group were obtained regio- and stereoselectively. The reaction mechanism was elucidated through isotope labeling experiments. The chemical properties of the lactones containing the trichloromethyl groups were investigated, and synthetic transformations of the product were realized.
BF3 ⋅ Et2O‐Mediated Annulation of 2‐Alkynyl Biaryls with N‐(Arylthio) Succinimides: An Efficient Approach to Access 9‐Sulfenylphenanthrenes
A simple and effective method for the synthesis of 9-sulfenylphenanthrenes was developed. The reaction proceeds through BF3 ⋅ OEt2-mediated annulation of 2-alkynyl biaryls with N-arylthio succinimides at room temperature. With this method, a series of 9-sulfenylphenanthrenes was efficiently obtained in good to excellent yields under mild and metal-free conditions.
Abstract
A simple and effective method for the synthesis of 9-sulfenylphenanthrenes was developed via BF3 ⋅ OEt2-mediated annulation of 2-alkynyl biaryls with N-arylthio succinimides at room temperature. Through this methodology, a series of 9-sulfenylphenanthrenes could be efficiently and conveniently obtained in good to excellent yields under mild and metal-free conditions.
Annulation via Ring Opening/Cyclization of Donor‐Acceptor Cyclobutanes with 2‐Naphthols: Access to Highly Functionalized Naphthalene‐Fused Oxepines
In this work, a mild and straightforward access to various substituted naphthalene-fused oxepines from readily available Donor-Acceptor (D-A) cyclobutanes and 2-naphthols is reported. A broad range of functional groups is tolerated during this transformation.
Abstract
A mild and straightforward access to various substituted naphthalene-fused oxepines from readily available Donor-Acceptor (D-A) cyclobutanes is reported. This method involves the Lewis acid-catalyzed reactions of D-A cyclobutanes with 2-naphthols to afford ring-opened products, which can undergo intramolecular cyclization mediated by the NBS-base system to yield corresponding naphthalene-fused oxepines. The cyclization protocol involves a nucleophilic attack of the oxygen of 2-naphthol on the newly formed electrophilic acceptor end of D-A cyclobutane.
Electrochemical Sulphenylation/Cyclization of Quinones: A Rapid, Green, and Efficient Access to Cytotoxic Compounds
Undivided electrochemical cells were utilized for sulphenylation reactions to prepare sulphur-containing naphthoquinones with potent bioactivity.
Abstract
Undivided electrochemical cells enable economical preparation of sulphur-containing naphthoquinones through electrochemical sulphenylation of quinoidal compounds. The environmentally friendly and efficient protocol eliminates the use of chemical oxidants and facilitates the synthesis of the desired molecules. This approach offers an efficient and versatile method to synthesize quinones that exhibit cytotoxicity against cancer cell lines.