Seven-membered Heterocycles Research Articles

4+3] Cycloaddition of Donor-Acceptor Cyclopropanes with Amphiphilic Benzodithioloimine as Surrogate for ortho-Bisthioquinone.

Donor-acceptor cyclopropanes were reacted with amphiphilic benzodithioloimine to give seven-membered heterocycles with two sulfur atoms. Formally, this transformation can be regarded as a [4+3] cycloaddition reaction of the three-membered ring and ortho-bisthioquinone. The benzodithioloimine serves as a surrogate for this highly reactive diene. The structure of the products was confirmed by X-ray crystallography. Broad signals in (13) C NMR studies suggest that several conformers, slowly interconverting on the NMR timescale, are present at room temperature.

Crystal structure of (Z)-7,8-di-chloro-4-(2-oxo-propyl-idene)-4,5-di-hydro-1H-1,5-benzodiazepin-2(3H)-one.

In the title compound, C12H10Cl2N2O2, the seven-membered heterocycle displays a half-chair conformation. The mean plane through the oxo­propyl­idene group makes a dihedral angle of 36.44 (9)° with the fused benzene ring. An intra­molecular N—H⋯O hydrogen bond to close an S(6) loop is noted. An important feature of the mol­ecular packing are N—H⋯O hydrogen bonds that lead to the formation of helical supra­molecular chains along the b axis.

Synthesis of Six- and Seven-Membered Heterocycles

Key words sulfonium salts - morpholines - piperazines - oxazepines - asymmetric synthesis

Gold-Catalyzed Ring Expansion of Alkynyl Heterocycles through 1,2-Migration of an Endocyclic Carbon-Heteroatom Bond.

A mild and efficient gold-catalyzed oxidative ring-expansion of a series of alkynyl heterocycles using pyridine-N-oxide as the oxidant has been developed, which affords highly valuable six- or seven-membered heterocycles with wide functional group toleration. The reaction consists of a regioselective oxidation and a chemoselective migration of an endocyclic carbon-heteroatom bond (favored over C-H migration) with the order of migratory aptitude for carbon-heteroatom bonds being C-S>C-N>C-O. In the absence of an oxidant, polycyclic products are readily constructed through a ring-expansion/Nazarov cyclization reaction sequence.

An Unprecedented Formal [5 + 2] Cycloaddition of Nitrones with o-Carboryne via Tandem [3 + 2] Cycloaddition/Oxygen Migration/Aromatization Sequence.

Heterocyclic skeletons are widespread among natural products as well as bioactive molecules. Cycloaddition reaction has created new opportunities to access heterocycles of great complexity due to its advantage of multiple bond formation in a single step. Here, we describe an unprecedented formal [5 + 2] cycloaddition of nitrone with o-carboryne to afford carborane-fused seven-membered heterocycles. Experimental and theoretical data suggest that a sequence of [3 + 2] cycloaddition, N-O bond cleavage, oxygen migration and rearomatization is involved in this unprecedented reaction. In this process, the nitrone moieties serve as five-atom coupling partners with both heteroatoms being incorporated into the framework of the final products. This new methodology also offers new insight into the chemistry of nitrones.

A Stable Seven-Membered Heterocycle, Containing B, C, N, O, and P Atoms, inside a Smaragdyrin Macrocycle.

Unprecedented examples of smaragdyrin macrocycles containing seven membered heterocyclic rings were synthesized under simple reaction conditions in high yields. The heterocycle formed inside smaragdyrin macrocycle is rare example of heterocycle containing five different atoms, such as B, C, N, O, and P atoms. The mixed B(III) and P(V) complexes of smaragdyrin macrocycles showed new structural, spectral, and electrochemical properties.

Metal-Free Decarboxylative Cyclization/Ring Expansion: Construction of Five-, Six-, and Seven-Membered Heterocycles from 2-Alkynyl Benzaldehydes and Cyclic Amino Acids

A one pot synthesis of 1H-benzo[g]indoles, tetrahydrobenzo[h]quinolines, and naphtho[1,2-b]azepines from 2-alkynyl benzaldehydes and cyclic amino acids is reported. The salient feature of the strategy involves formation of three new bonds (one CN and two CC bonds) by a metal-free decarboxylation/cyclization/one-carbon ring expansion sequence in one pot.

2-(5-Methyl-2-Phenyl-2H-1,2,3-Dizaphosphol-4-YL)-4H-Benzo[D]-1,3,2-Dioxaphosphorin-4-One in the Synthesis of Bis-Heterocyclic 1,4,2-Oxazaphosphepine Derivatives

GRAPHICAL ABSTRACT

ChemInform Abstract: Catalytic Hydroamination of Unactivated Olefins Using a Co Catalyst for Complex Molecule Synthesis.

Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.

Seven-Membered Heterocycles by Chlorosilane-Catalyzed Heteroannulation

Seven-Membered Heterocycles by Chlorosilane-Catalyzed Heteroannulation

Ring-strain-enabled reaction discovery: new heterocycles from bicyclo[1.1.0]butanes.

Mechanistically as well as synthetically, bicyclo[1.1.0]butanes represent one of the most fascinating classes of organic compounds. They offer a unique blend of compact size (four carbon atoms), high reactivity (strain energy of 66 kcal/mol), and mechanistic pathway diversity that can be harvested for the rapid assembly of complex scaffolds. The C(1)-C(3) bond combines the electronic features of both σ and π bonds with facile homolytic and heterolytic bond dissociation properties and thereby readily engages pericyclic, transition-metal-mediated, nucleophilic, and electrophilic pathways as well as radical acceptor and donor substrates. Despite this multifaceted reaction profile and recent advances in the preparation of bicylo[1.1.0]butanes, the current portfolio of synthetic applications is still limited compared with those of cyclopropanes and cyclobutanes. In this Account, we describe our work over the past decade on the exploration of substituent effects on the ring strain and the reactivity of bicyclo[1.1.0]butanes, particularly in the context of metal-mediated processes. We first describe Rh(I)-catalyzed cycloisomerization reactions of N-allyl amines to give pyrrolidine and azepine heterocycles. The regioselectivity of the C,C-bond insertion/ring-opening step in these reactions is controlled by the phosphine ligand. After metal carbene formation, an intramolecular cyclopropanation adds a second fused ring system. A proposed mechanism rationalizes why rhodium(I) complexes with monodentate ligands favor five-membered heterocycles, as opposed to Rh(I)-bidentate ligand catalysts, which rearrange N-allyl amines to seven-membered heterocycles. The scope of Rh(I)-catalyzed cycloisomerization reactions was extended to allyl ethers, which provide a mixture of five- and seven-membered cyclic ethers regardless of the nature of the phosphine additive and Rh(I) precatalyst. The chemical diversity of these cycloisomerization products was further expanded by a consecutive one-pot metathesis reaction. Rh(I)-catalyzed cycloisomerizations of propargyl amides, ethers, and electron-deficient bicyclo[1.1.0]butanes diverged mechanistically and often led to a significant number of decomposition products. In these cases, Pt(II) emerged as a superior, more alkynophilic late transition metal with its own mechanistic peculiarities. While monosubstituted bicyclo[1.1.0]butanes led to the formation of tetrahydropyridines, 1,3-disubstituted and electron-deficient bicyclo[1.1.0]butanes reacted distinctly differently with Pt(II) and ultimately provided a complementary set of nitrogen- and oxygen-containing cyclic scaffolds. The metal-catalyzed ring transformations of bicyclo[1.1.0]butanes presented herein suggest additional strategies for new reaction discoveries that can access a wide variety of novel cyclic frameworks from relatively simple starting materials. In addition, these case studies highlight the considerable potential for future applications in natural products, medicinal, and diversity-oriented synthesis based on the wealth of mechanistic pathways available to these strained small-ring carbocycles.

Synthesis of Common-sized Heterocyclic Compounds by Intramolecular Cyclization over Halide Cluster Catalysts

Abstract Five- to seven-membered common-sized heterocyclic compounds containing an oxygen, sulfur, or nitrogen were synthesized by the intramolecular condensation of α,ω-hydroxy, mercapto, or amino alkanes, respectively, over halide cluster complexes as a thermally stable molecular solid weak acid catalyst in the gas phase at temperatures ≥150 °C. From ω-mercapto and ω-amino alcohols, cyclic sulfides and amines were obtained, respectively. These unimolecular reactions are thermodynamically and kinetically favored.

Pharmacological and synthetic profile of benzothiazepine: A review

The 1, 5-benzothiazepines are important nitrogen- and sulfur-containing seven-membered heterocyclic compounds in drug research since they possess diverse bioactivities. 1, 5-Benzothiazepines are the most well-known representatives of benzologs of 1,4-thiazepine and one of the three possible benzo-condensed derivatives, and 1,5-benzothiazepines. The 1, 5-benzothiazepine derivatives are of particular interest for lead discovery because they have been found active against different families of targets.Therefore, the 1,5-benzothiazepines are useful compounds in the drug research which has stimulated the invention of a wide range of synthetic methods for their preparation and chemical transformations. Benzothiazepine and its derivatives exhibit diverse biological activities such as coronary vasodilatory, tranquilizer, antidepressant, antihypertensive, calcium channel blocker. This review also discusses the structure-activity relationship of the most potent compounds. It can act as an important tool for medicinal chemists to develop newer compounds possessing 1, 5-benzothiazepines moiety that could be better agents in terms of efficacy and safety.

ChemInform Abstract: Direct Inter‐ and Intramolecular Addition of Amides to Arylalkenes Promoted by KOt‐Bu/DMF.

Direct addition of tetrahydroisoquinoline derived amides to arylalkenes has been achieved in the presence of KOt-Bu/DMF. Both intermolecular and intramolecular reactions could occur in good yields. α-Amido alkyl radicals are proposed to be generated under the reaction conditions. The reaction is efficient for the synthesis of seven-membered nitrogen heterocycles. A homoprotoberberine was prepared conveniently via this method.

Ring expansion reactions of pentaphenylborole with dipolar molecules as a route to seven-membered boron heterocycles.

Reactions of pentaphenylborole with isocyanates, benzophenone, and benzaldehyde produced new seven-membered heterocycles in high yields. For 1-adamantyl isocyanate, a BNC5 heterocycle was obtained from the insertion of the C-N moiety into the five-membered borole, whereas for 4-methoxyphenyl isocyanate, a BOC5 heterocycle was generated from the insertion of the C-O unit. These reactions are believed to occur via a mechanism wherein coordination of the nucleophile to the borole (1-adamantyl, N-coordination or O-coordination for 4-methoxyphenyl) is followed by ring expansion to afford the observed seven-membered heterocycles. The selectivity to form B-O- or B-N-containing heterocycles is based on the polarization of the isocyanate implying tunable reactivity for the system. Having observed that isocyanates react as 1,2-dipoles with pentaphenylborole, we examined benzophenone and benzaldehyde, which both reacted to insert C-O units into the ring. This represents a new efficient method for preparing rare seven-membered boracycles.

ChemInform Abstract: Penioxalamine A, a Novel Prenylated Spiro‐Oxindole Alkaloid from Penicillium oxalicum TW01‐1.

Abstract Penioxalamine A (1), a novel prenylated spiro-oxindole alkaloid having a unique seven-membered nitrogen heterocycle system, was isolated from the fungus Penicillium oxalicum TW01-1. The structure of 1 was elucidated on the basis of the spectral data, single-crystal X-ray diffraction, and CD analysis. Compound 1 showed moderate cytotoxicity against HL-60 cell line. The possible biosynthetic pathway of 1 was also proposed.

Synthesis of Pyrido-Annelated Seven-Membered N-Containing Heterocycles

Pharmaceutical industry is struggling with a lack of potential drugs in the pipe line. However, there is still a great opportunity to elaborate interesting scaffolds for medicinal chemistry. Various scaffolds that hold promise are rarely described in the literature. The last couple of decades, the wide range of biological activities of benzodiazepine derivatives have been investigated thoroughly and make the benzodiazepine scaffold, particularly the 1,4-benzodiazepine system, one of the most important structures for drug discovery. The substantial research on benzodiazepines has led to the synthesis of heterocycle-fused azepine derivatives with potentially new pharmacological activity. Some pyridoazepines are known to be active in the central nervous system and have a comparable activity to the well-known benzodiazepine scaffolds, which make the synthesis and study of pyridoazepines an important research topic.

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 3 by MeSiCl3/DMF-catalyzed domino reaction via the addition of in situ generated enamines to aldehydes 1. 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 4, which may have potential application in drug industry.

ChemInform Abstract: Microwave‐Assisted Synthesis of Seven‐Membered S‐Heterocycles

AbstractReview: 78 refs.

Catalytic hydroamination of unactivated olefins using a Co catalyst for complex molecule synthesis.

Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.