Seven-membered Heterocycles Research Articles

Oxidation of azidoalkyl furans

The oxidation reactions of various azidoalkyl furans were explored under different conditions to access structurally complex compounds from simple starting materials in an operationally simple, single step reaction. The strategically placed azide functional groups on the alkyl chain of the furan led to the discovery of a new and simple method for the synthesis of five-, six-, and seven-membered nitrogen heterocycles bearing prochiral centers and stereocenters.

Phosphine-Catalyzed Enantioselective [4 + 3] Annulation of Allenoates with C,N-Cyclic Azomethine Imines: Synthesis of Quinazoline-Based Tricyclic Heterocycles.

With the use of a commercially available chiral phosphine as the catalyst, the first catalytic enantioselective [4 + 3] annulation of allenoates with C,N-cyclic azomethine imines is developed. The reaction works efficiently under mild reaction conditions to afford seven-membered ring-fused quinazoline-based tricyclic heterocycles in high yields with good to excellent diastereo- and enantioselectivities.

The Synthesis of 5-Amino-dihydrobenzo[b]oxepines and 5-Amino-dihydrobenzo[b]azepines via Ichikawa Rearrangement and Ring-Closing Metathesis.

The combination of Ichikawa's rearrangement and a ring-closing metathesis reaction of allyl carbamates is presented as a method for the preparation of 5-amino-substituted 2,5-dihydro-benzo[b]oxepines, 2,5-dihydro-benzo[b]azepines, and 2,5-dihydro-benzo[b]thiepins. It was demonstrated that the use of nonracemic allyl carbamates enables the synthesis of enantioenriched benzo-fused seven-membered heterocycles. Finally, it was shown that further functionalization of the obtained structures allows access to pharmacologically active 5-amino-substituted 2,3,4,5-tetrahydro-1-benzo[b]oxepine scaffolds.

ChemInform Abstract: The Formation of Seven‐Membered Heterocycles under Mild Pictet—Spengler Conditions: A Route to Pyrazolo[3,4]benzodiazepines.

Reported is a method for the synthesis of seven-membered heterocycles via a Pictet–Spengler condensation reaction under very mild conditions. High substrate scope allows for use of aldehydes using catalytic amounts of acetic acid yielding 39–90% and ketones using catalytic amounts of trifluoroacetic acid yielding 25–83%.

Conformational isomerism of the seven-membered heterocycle in a single crystal of [η2-Ph2P(O)(CH2)2C(O)NМе2]TiF4 adduct

The crystal structure of TiF4[(Ph2P(O)CH2CH2C(O)NMe2)] chelate (I) was studied by X-ray crystallography, which revealed four crystallographically independent complex molecules of similar structure (1–4). It was found that the molecules are only slightly different in the bond lengths between the coordinated atoms and the central titanium ion and considerably different in the geometry of the seven-membered TiOPCCCO chelate ring. The geometry of the chelate rings was found to be almost identical in each pair of complexes 1, 2 (A) and 3, 4 (B), and a conclusion was drawn on the presence of two conformational isomers (A and B) of the chelate complex. Quantum chemical calculations of the relative thermodynamic stability of molecules 1–4 were performed, and their geometry optimization led to one theoretical structure. The comparison of the chelate ring geometry in the theoretical structure and in conformers A and B revealed that the conformation of the theoretical chelate ring coincides with that of conformer A.

Gold-Catalyzed Formal [4+1]/[4+3] Cycloadditions of Diazo Esters with Triazines.

Reported herein is the unprecedented gold-catalyzed formal [4+1]/[4+3] cycloadditions of diazo esters with hexahydro-1,3,4-triazines, thus providing five- and seven-membered heterocycles in moderate to high yields under mild reaction conditions. These reactions feature the use of a gold complex to accomplish the diverse annulations and the first example of the involvement of a gold metallo-enolcarbene in a cycloaddition. It is also the first utilization of stable triazines as formal dipolar adducts in the carbene-involved cycloadditions. Mechanistic investigations reveal that the triazines reacted directly, rather than as formaldimine precursors, in the reaction process.

Asymmetric Synthesis of Spirobenzazepinones with Atroposelectivity and Spiro-1,2-Diazepinones by NHC-Catalyzed [3+4] Annulation Reactions.

A strategy for the NHC-catalyzed asymmetric synthesis of spirobenzazepinones, spiro-1,2-diazepinones, and spiro-1,2-oxazepinones has been developed via [3+4]-cycloaddition reactions of isatin-derived enals (3C component) with in-situ-generated aza-o-quinone methides, azoalkenes, and nitrosoalkenes (4atom components). The [3+4] annulation strategy leads to the seven-membered target spiro heterocycles bearing an oxindole moiety in high yields and excellent enantioselectivities with a wide variety of substrates. Notably, the benzazepinone synthesis is atroposelective and an all-carbon spiro stereocenter is generated.

Deep eutectic solvent as a highly efficient reaction media for the one-pot synthesis of benzo-fused seven-membered heterocycles

The combination of choline chloride and urea as a deep eutectic solvent has been applied to the synthesis of benzo-fused seven-membered heterocycles, including tricyclic 1,4-benzodiazepines and 1,4-benzoxazepines, via a one-pot, three-component reaction. The reaction conditions are relatively mild and do not require additional metals, acid catalysts, or organic solvents. The protocol has the advantages of excellent yields in short reaction times, an easy workup procedure, and being environmentally friendly.

Synthesis of Six- and Seven-Membered Chloromethyl-Substituted Heterocycles via Palladium-Catalyzed Amino- and Oxychlorination

The synthesis of six- and seven-membered chloromethyl-substituted heterocycles, such as piperazinone, tetrahydroquinoxaline, benzodiazepinone, and benzoxazepinone, is reported using palladium-catalyzed vicinal diheterofunctionalization of nonactivated alkenes. The reaction conditions for this domino process are soft and mild, and the chloromethyl appendage allows various post-functionalizations via simple nucleophilic substitutions.

Novel oxazepinedione-derived symmetric dimers: synthesis and mesophase characterisation of seven-membered heterocyclic compounds

ABSTRACTThe synthesis and characterisation of three sets of symmetric dimeric compounds composed of seven-membered oxazepinedione heterocyclic rings were carried out. All the dimers possess the tetradecyl- (n = 14) alkyl side chain attached to the nitrogen atom of the oxazepinedione core. The oxazepinedione core in turn was connected with varied connecting spacers (n = 4, 6, 8, 10 and 12). The dimers were spectroscopically characterised by FT-IR, 1H-NMR, 13C-NMR and elemental analysis techniques. The compounds were investigated for liquid crystalline properties using differential scanning calorimetry and polarising optical microscopy with heating assembly. The precursor imines 2a–e itself started exhibiting liquid crystalline SmA/tilted hexatic mesophase. Further fusion of 2a–e with maleic anhydride, succinic anhydride and phthalic anhydride gave the novel oxazepinedione-derived symmetric dimers 3a–e, 4a–e and 5a–e respectively. The dimers 3a–e and 4a–e did not exhibit any liquid crystal (LC) properties. However, the phthalic anhydride-fused oxazepinediones 5a–e show monotropic nematic liquid crystalline phase. The results indicate that the formation of mesophase is dependent on the type of fused oxazepinedione ring.

Towards Uniform Iodine Catalysis: Intramolecular C-H Amination of Arenes under Visible Light.

A photochemical catalytic amination of arenes is presented. The reaction proceeds under benign iodine catalysis in the presence of visible light as the initiator and provides access to a range of differently substituted arylamines. A total of 29 examples demonstrate the broad applicability of this mild oxidation method. The scope of the reaction could further be expanded to silyl-tethered derivatives, which undergo intramolecular amination upon formation of seven-membered heterocycles. Cleavage of the silicon tether provides access to the corresponding 3-substituted anilines.

ChemInform Abstract: Synthesis of Organofluoro Compounds Using Methyl Perfluoroalk‐2‐ynoates as Building Blocks

AbstractReview: [47 refs.

Mixed Boron(III) and Phosphorous(V) Complexes of meso-Triaryl 25-Oxasmaragdyrins.

Two unprecedented mixed B(III) /P(V) complexes of meso-triaryl 25-oxasmaragdyrins were synthesized in appreciable yields under mild reaction conditions. These unusual 25-oxasmaragdyrin complexes containing one or two seven-membered heterocyclic rings comprised of five different atoms (B, C, N, O, and P) were prepared by reacting B(OH)(Ph)-smaragdyrin and B(OH)2 -smaragdyrin complexes, respectively, with POCl3 in toluene at reflux temperature. The products were characterized by HRMS and 1D- and 2D-NMR spectroscopy. X-ray crystallography of one of the mixed B(III) /P(V) smaragdyrin complexes indicated that the macrocycle is significantly distorted and contains a stable seven-membered heterocyclic ring within the macrocycle. The bands in the absorption and emission spectra were bathochromically shifted with reduced quantum yields and singlet-state lifetimes relative to the free base, meso-triaryl 25-oxasmaragdyrin. The mixed B(III) /P(V) complexes were difficult to oxidize but easier to reduce than the free base. The DFT-optimized structure of the 25-oxasmaragdyrin complex with two seven-membered heterocycles indicated that it was a bicyclic spiro compound with two half-chair-like conformers. This was in contrast to the chair-like conformation of the complex with a single seven-membered heterocyclic ring. Moreover, incorporation of a second phosphate group in the former case stabilized the bonding geometry and resulted in higher stability, which was reflected in the bathochromic shift of the absorption spectra, more-positive oxidation potential, and less-negative reduction potential.

The Formation of Seven-Membered Heterocycles under Mild Pictet-Spengler Conditions: A Route to Pyrazolo[3,4]benzodiazepines.

Reported is a method for the synthesis of seven-membered heterocycles via a Pictet-Spengler condensation reaction under very mild conditions. High substrate scope allows for use of aldehydes using catalytic amounts of acetic acid yielding 39-90% and ketones using catalytic amounts of trifluoroacetic acid yielding 25-83%.

Synthesis of Azepane Derivatives by Silyl-aza-Prins Cyclization of Allylsilyl Amines: Influence of the Catalyst in the Outcome of the Reaction.

The synthesis of seven-membered nitrogen heterocycles by silyl-aza-Prins cyclization is described. The process provides trans-azepanes in high yields and good to excellent diastereoselectivities. Moreover, the reaction outcome is dependent on the Lewis acid employed. Thus, while azepanes are selectively obtained when InCl3 is used, the reaction in the presence of TMSOTf provides tetrahydropyran derivatives corresponding to a tandem Sakurai-Prins cyclization.

Specifics of titanium tetrafluoride complexation with Ph2P(O)(CH2)2C(O)NMe2: The remarkable stability of the seven-membered chelate heterocycle TiOPCCCO and its conformational isomerism in solution

The composition and structure of the products of the reaction of titanium tetrafluoride with Ph2P(O)(CH2)2C(O)NМе2 (L), the simplest representative of diphenyl[2-(N,N-dialkylcarbamoyl)ethyl]phosphine oxides, in a СН2Сl2 have been studied by 19F and 31P NMR. It has been shown for the first time that functionalized phosphine oxides form stable seven-membered chelate heterocycles on complexes of d° transition metals. On the basis of NMR data, previously unknown conformational isomerism of the seven-membered TiOPCCCO heterocycle in solution has been proposed. A simple and rather efficient method of synthesis of the ligand (L) from commercially available reagents has been developed.

Synthesis of Organofluoro Compounds Using Methyl Perfluoroalk-2-ynoates as Building Blocks.

This review provides an overview of several synthetic applications of methyl perfluoroalk-2-ynoates, leading to convenient preparation of many perfluoroalkylated compounds. The use of these important substrates in the synthesis of various five-, six-, and seven-membered heterocycles, cyclopentadienes, and biphenyls is described, alongside a discussion of the mechanistic aspects of these reactions.

Porphyrin Macrocycle Modification: Pyrrole Ring-Contracted or -Expanded Porphyrinoids.

In recent years, several synthetic strategies aiming at the peripheral functionalization of porphyrins were developed. Particularly interesting are those involving the modification of β-pyrrolic positions leading to pyrrole-modified porphyrins containing four-, five-, six- or seven-membered heterocycles. Azeteoporphyrins, porpholactones and morpholinoporphyrins are representative examples of such porphyrinoids. These porphyrin derivatives have recently gained an increasing interest due to their potential application in PDT, as multimodal imaging contrast agents, NIR-absorbing dyes, optical sensors for oxygen, cyanide, hypochlorite and pH, and in catalysis.

ChemInform Abstract: A Facile and Efficient Approach to Seven‐Membered Heterocycles by Chlorosilane‐Catalyzed Domino Reaction.

A facile and efficient method has been developed for the preparation of seven-membered heterocycles 1,5-benzoxazepines by MeSiCl3/DMF-catalyzed domino reaction via the addition of in situ generated enamines to aldehydes . The advantages of this method are that it operates easily and achieves good yields for a broad scope of aldehyde substrates. And the corresponding products can be readily transformed to other categories of compounds, such as the hydrogenated products , which may have potential application in drug industry.

Synthesis of substituted quinolinone ketones derived with some five, six and seven-membered heterocycles

Abstract: The synthesis of a series of new quinolinyl ketones substituted with some five, six and seven-membered diaza-heterocycles is described. Efficient base or acid-catalyzed nucleophilic heterocyclization of 6-ethyl-4,5-dioxo-5,6-dihydro-4 H -pyrano[3,2- c ]quinoline-3-carboxaldehyde with a variety of nitrogen and/or carbon 1,2-, 1,3-, and 1,4-binucleophiles afforded the target ketones in good yields. The structure of all new products was established on basis of their spectral and analytical data.