Convenient syntheses of benzo-fluorinated dibenz[b,f]azepines: rearrangements of isatins, acridines, and indoles

Efficient procedures for the synthesis of benzo-fluorinated dibenz[b,f]azepines (iminostilbenes) from fluorinated isatins or indoles using a number of ring-expansion reactions are described. A range of mono- and difluorinated analogues is accessible, and the syntheses can deliver gram quantities of the final products, which are precursors of fluoro analogues of the important anticonvulsant carbamazepine.     

第5/6副族高价过渡金属氯化物的有机反应

从制备化学的角度, 对包括作者本人的研究工作在内的由第5/6副族高价过渡金属氯化物参加的有机反应进行了综述. 内容包括以下几个方面: (1)烷烃、烯烃和炔烃与第5/6副族高价过渡金属氯化物的卤化反应; (2)作为Lewis 酸催化的反应; (3)烯烃歧化反应及炔烃的聚合反应; (4) MoCl₅参与的芳烃氧化偶合反应; (5)硫醚化及扩环反应.     

Ring-opening and ring-expansion reactions of carborane-fused borirane

Though the reaction chemistry of three-membered ring molecules such as cyclopropanes and their heteroatom-containing analogues has been extensively studied, the chemical properties of their boron analogues, boriranes, are little known thus far. This work describes the diverse reactivity patterns of carborane-fused borirane 2. This borirane engages in ring-opening reactions with different types of Lewis acids, such as BBr₃, GeCl₂, GaCl₃, BH₃(SMe₂) and HBpin, affording a series of ring-opening products, in which M–X or B–H bonds add across the B–C(cage) bond of the three-membered ring in 2. On the other hand, borirane 2 can undergo ring-expansion reactions with unsaturated molecules such as PhCHO, CO₂ and PhCN to give ring-expansion products, five-membered boracycles, via a concerted reaction mechanism as supported by DFT calculations. The results of this work not only enrich the reaction chemistry of boriranes, but also offer new routes to boron-containing compounds and heterocycles.

Carborane-fused borirane can not only engage in ring-opening reactions with different types of Lewis acids, but also undergo ring-expansion reactions with unsaturated molecules such as PhCHO, CO₂ and PhCN to give five-membered boracycles.     

A photo-reagent system of benzimidazoline and Ru(bpy)3Cl2 to promote hexenyl radical cyclization and Dowd–Beckwith ring-expansion of α-halomethyl-substituted benzocyclic 1-alkanones

A combination of 2-aryl substituted 1,3-dimethyl-benzimidazolines (DMBIHs) and tris(2,2′-bipyridine)ruthenium(II) chloride, Ru(bpy)₃Cl₂ was used to promote photoinduced electron-transfer (PET) reactions of α-halomethyl-substituted benzocyclic 1-alkanones. This photo-reagent system stimulates free radical forming, cleavage of both carbon–bromine and carbon–chlorine bonds that are not activated by carbonyl groups. The resulting free radicals undergo 5-exo hexenyl cyclization as well as sequential cyclization and ring-expansion (Dowd–Beckwith) reactions to form radicals that abstract hydrogen atoms from the radical cation of DMBIH to yield the observed products. The results of a study of the effects of substituents located on the 2-aryl ring of DMBIH suggest that steric and hydrogen-bonding interactions influence the nature of the reaction pathways followed by the radical intermediates. PET reactions using an iridium complex and DMBIH were also investigated.     

Synthesis of seven-membered ring diazepin-2-ones via palladium-catalyzed highly regioselective cyclization of 2-vinylpyrrolidines with aryl isocyanates

The first palladium-catalyzed ring-expansion reaction of 2-vinylpyrrolidines with aryl isocyanates to form seven-membered ring heterocycles is described. This regioselective reaction requires 5 mol % of Pd(2)(dba)(3).CHCl(3) and 10 mol % of dppp at 40-60 degrees C in THF and results in the formation of 1,3-diazepin-2-ones in good isolated yields. When Pd(OAc)(2) and PPh(3) were utilized in the reaction, an intramolecular hydrogen migration occurs resulting in the formation of conjugated diene derivatives of urea.     

An improved catalyst system for the iron-catalyzed intermolecular ring-expansion reactions of epoxides

A considerable improvement is reported in the iron-catalyzed ring-expansion reactions of epoxides generating tetrahydrofuran derivatives by formal insertion of an alkene. Optimization of the catalyst system revealed that a preformed [Fe(salen)] complex minimizes the formation of polymerization side-products so that increased yields of intermolecular reactions were obtained. However, more importantly, the scope of the reaction could also be enlarged considerably. The iron-catalyzed ring-expansion reaction can now be applied to some styrene oxide derivatives, acting as radical donors, as well as to a wide variety of acceptor-substituted acyclic alkenes and cyclic dienes that act as radical acceptors. The use of unsymmetrical radical acceptors led to interesting questions concerning the regiochemistry of the reactions. The conservation of the stereochemistry of the starting materials in the products was investigated through a study of the reactions of E- and Z-configured acceptor-substituted double bonds. The reactions of fumaric and maleic esters were performed and the ratios of diastereomeric and regioisomeric products were determined.     

Enantioselective synthesis of pyranonaphthoquinone antibiotics using a CBS reduction/cross-metathesis/oxa-Michael strategy

The enantioselective syntheses of deoxydihydrokalafungin (5), cis-deoxydihydrokalafungin (6) and deoxykalafungin (7) are reported. The strategy was based on 4 key reactions: (1) CBS reduction of prochiral ketone 10 to introduce chirality at C-1, (2) radical allylation of quinone 9a, (3) cross-metathesis of dimethoxynaphthalene 13 with methyl acrylate, and (4) intramolecular oxa-Michael addition of alcohol 8 to form the core naphthopyran ring system. This novel approach delivers naphthopyrans possessing the natural trans-stereochemistry observed in the pyranonaphthoquinone family of antibiotics.     

Divergent enantioselective synthesis of (-)-galanthamine and (-)-morphine

An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.     

1,3-Diphosphetane-2,4-diyles--Cryptocarbenes?

1,3-Diphosphetane-2,4-diyles ( A ) possess a diradical molecular structure. Experimental studies reveal interconversions of different valence isomers of the diradicals. As a consequence of the facile thermal ring opening of 1,3-diphosphetane-2.4-diyles A , we obtained crypto-phosphinocarbenes ( B ), confirmed by the results of intramolecular rearrangements as well as reactions with multiple bonded systems. A new range of five- and six-membered phosphorus heterocycles are isolated, including transition-metal complexes. The mechanism for the ring-expansion are predicted by quantum chemical calculations.     

Studies on intramolecular 1,3-dipolar cycloaddition reactions: III. The synthesis of a novel heterocyclic ring system by regiospecific cycloaddition

The syntheses of a number of C-aryl-N-3-butenyl nitrones [aryl ring=4-CH₃O-phenyl ( 1a ), phenyl ( 1b ), 4-Cl-phenyl ( 1c ), 4-Br-phenyl ( 1d ), 4-NO₂-phenyl ( 1e ), 2-furyl (1f), 2-thienyl ( 1g ), 2-pyrryl ( 1h )] and their thermochemical reactions have been investigated. The thermocycloadditions of 1a–1h are regiospecific in forming a novel heterobicyclic ring system, exo-aryl-1-aza-7-oxabicyclo-[2.2.1]heptane.     

Two syntheses of the 16- and 17-membered DEF ring systems of chloropeptin and complestatin

[formula: see text] Two syntheses of a model system of the DEF ring system of complestatin and chloropeptin are described. The key step in both of these syntheses involves the formation of the biaryl linkage using a palladium-catalyzed Suzuki cross-coupling reaction and a catalytic enantioselective ene reaction to form the 6-bromo-D-tryptophan. Additionally, ring contraction of the 17-membered DEF ring system of complestatin generates the 16-membered DEF ring system of chloropeptin in a biomimetic fashion.     

The reactivity of small-ring monostannacycloalkanes : III. Ring-expansion reactions of 1,1-dimethyl-1-stannacyclopentane

As a result of the enhanced reactivity of the endo-cyclic tincarbon bond 1,1-dimethyl-1-stannacyclopentane readily undergoes ring-expansion reactions with a variety of substrates to produce new organotin heterocycles. Illustrative examples include ring-expansion reactions with oxygen, sulphur, sulphur dioxide, diiron noncarbonyl, dichlorocarbene and diethyl azodicarboxylate.     

Concise, asymmetric, stereocontrolled total synthesis of stephacidins A, B and notoamide B

Concise asymmetric total syntheses of the fungal metabolites (-)-stephacidin A, (+)-stephacidin B, and (+)-notoamide B are described. Key features of these total syntheses include (1) a facile synthesis of (R)-allyl proline methyl ester, (2) a revised route toward the pyranoindole ring system, (3) a novel cross-metathesis strategy for the introduction of important functional groups, and (4) an SN2' cyclization to form the [2.2.2] bridged bicyclic ring system. Furthermore, our synthesis has taken advantage of microwave heating to shorten reaction times as well as increase yields for the preparation of vital intermediates.     

Synthesis of Pyridazine and Pyrrole Analogues of 2‐Aminotetralin as Potential Dopaminergics

Syntheses of pyridazine and pyrrole analogues of 2‐aminotetralin starting from 3‐cyclohexene‐1‐carboxylic acid are reported. All syntheses involve the following key steps: Curtius rearrangement for amine functionality, inverse electron demand Diels–Alder addition with 1,2,4,5‐tetrazine for pyridazine ring synthesis, and pyridazine‐to‐pyrrole ring contraction for pyrrole ring formation.     

3-Amino-2H-Azirines. Synthons for α,α-Disubstituted α-Amino Acids in Heterocycle and Peptide Synthesis [New Analytical Methods (43)]

The recent upswing in peptide chemistry has been accompanied by an increasing interest in nonproteinogenic amino acids. These include the α,α-disubstituted glycines, the best known of which is Aib (2-aminoisobutyric acid, 2-methylalanine). These α-amino acids occur in natural oligopeptides such as the peptaibols, a class of membrane-active ionophores that has been isolated from fungal cultures. The twofold substitution at the α-C atom of the amino acids severely restricts the conformational freedom of the peptides and causes particular secondary structures to be favored; thus, α, α-disubstituted α-amino acids induce the formation of β turns or helices. 3-Amino-2H-azirines are ideal synthons for the construction of oligopeptides, cyclic peptides and depsipeptides (peptolides) containing such α,α-disubstituted α-amino acids. The presence of the ring strain in these molecules means that they can be used in peptide coupling without the need for additional activating reagents. Using 3-amino-2H-azirines a large array of heterocycles containing α, α-disubstituted α-amino acids as structural elements within their skeleton can be synthesized. The driving force in these reactions is the release of the strain on the three-membered ring, which usually takes place in a ring-expansion reaction. The mechanistic elucidation of these reactions, which can be quite complex, contains some surprises.     

Carbonyl group‐containing organometallic intramolecular‐coordination five‐membered ring compounds

Carbonyl group‐containing organometallic intramolecular‐coordination five‐membered ring compounds are easily synthesized by the following five reaction methods: (1) cyclometalation, especially, orthometalation reactions; (2) the reactions of the moieties of an unsaturated carbon? carbon bond attached to a carbonyl group (C?C? CO, C?C? CO); (3) the reactions of an unsaturated carbon? carbon bond with carbon monoxide (C?C and CO, C?C and CO); (4) carbonylative ring expansion reactions; and (5) others. These compounds are very easily and regio‐specifically synthesized with many kinds of metal compounds, including both transition metals and main group metals. Many of such the reactions are easily applied to organic syntheses. Copyright © 2010 John Wiley & Sons, Ltd.     

Ring-expansion reaction of oximes with aluminum reductants

The ring-expansion reactions of heterocyclic ketoximes and carbocyclic ketoximes with several reductants such as AlHCl2, AlH3 (alane), LiAlH4, LiAlH(OtBu)3, and (MeOCH2CH2O)2AlH2Na (Red-Al) were examined. Among reductants, AlHCl2 (LiAlH4:AlCl3 = 1:3) in cyclopentyl methyl ether (CPME) has been found to be a suitable reagent for the reaction, and the rearranged cyclic secondary amines were obtained in good to excellent yields.     

Elucidation of a Dearomatization Route in the Biosynthesis of Oxysporidinone Involving a TenA-like Cytochrome P450 Enzyme

Oxidative dearomatization of phenols is an important transformation for synthesis of complex molecules. Oxysporidinone and related 2-pyridones feature a hydroxy-substituted cyclohexanone ring, which has been proposed to form by phenol dearomatization, although the details of the biochemical process are still unknown. In this study, we identified the oxysporidinone biosynthetic gene cluster in Fusarium oxysporum by regulator activation and gene knockout studies. Through in vivo and in vitro studies, we confirmed that the phenol dearomatization process involves two enzymes. OsdM, a TenA-like cytochrome P450 with expected ring-expansion activity, converts the phenol ring and the 4-hydroxy-2-pyridone core into an unexpected fused [6-5-6] ring system. OsdN, on the other hand, catalyzes two successive ene reduction reactions, followed by hydroxylation by OsdM. This new route enriches current knowledge on enzymatic phenol dearomatization and the mechanism of TenA-like P450s.     

Synthetic procedure for various selenium-containing electron donors of the bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF) type

Six selenium variants of BEDT-TTF have been successfully synthesized by a newly developed synthetic method that involves a combination of two key reactions for the construction of two kinds of heterocyclic rings: the first is a one-pot formation of 1,3-dichalcogenole-2-chalcogenones from a common starting material, THP-protected 2-(ethynylthio)ethanol, leading to the inner five-membered rings, and the other is the annelation of the outer six-membered heterocyclic ring onto the inner ring by an intramolecular transalkylation reaction on a chalcogen atom. This method turned out to be widely applicable to the syntheses of the electron donors of bis(ethylenedithio)- and bis(ethyleneselenothio)-substituted types. However, synthetic attempts to form analogous donors of the bis(ethylenediseleno)-substituted type from THP-protected 2-(ethynylseleno)ethanol were unsuccessful. This is attributable to the predominance of side-reactions via a seleniranium (episelenonium) salt over the desired six-membered ring formation by transalkylation via a seleninium salt.