Indazolequinones in the Nenitzescu Reaction. Synthesis of Pyrrolo[2,3-e]- and Furo[2,3-e]indazoles

A heterocyclic quinone was used in the Nenitzescu reaction for the first time. New tricyclic compounds - pyrrolo[3,2-e]- and furo[3,2-e]indazoles - were synthesized by the condensation of 1,3-diphenyl-4,7-dioxoindazole with various enamines.     

Transformations of 2,2,6-trimethyl-1,3-dioxen-4-one with heterocyclic amines and other amino compounds

Heterocyclic amines were acetoacetylated with 2,2,6-trimethyl-1,3-dioxen-4-one and the obtained compounds reacted on the reactive methylene group to give C-substituted products. Nitrosation, followed by reduction afforded a pyrazine derivative. Azido- or chloroacetamide were also acetoacetylated, with heterocyclic amines, the corresponding enamines were prepared and reduction of the azido group of 15 afforded compounds 22 and/or amides of substituted 3-oxobutanoic acid 23 . An X-ray structural determination of compound 23a revealed that the orientation about the double bond is Z.     

Neuartige Merocyanine vom Typ des «Bindons»

The title compounds (new type of merocyanines) were obtained from the reaction of heterocyclic enamines with indan-1,3-dione, biindantrione, 2-(3-methoxy-inden-1-yliden)-indan-1, 3-dione, or 2-(3-chloro-inden-1-yliden)-indan-1, 3-dione respectively. The enamines were obtained from the corresponding quaternary salts and reacted in situ.     

Chemical behavior of 4,9-dimethoxy-5-oxo-5H-furo[3,2-g]chromene-6-carboxaldehyde towards carbon nucleophilic reagents

The chemical behavior of 6-formylkhellin ( 1 ) was investigated toward a variety of carbon nucleophiles. Treatment of aldehyde 1 with cyanoacetamide, N-benzylcyanoacetamide produced pyridine-3-carboxamides 3 and 4 . Treatment of carboxaldehyde 1 with malononitrile dimer and 1H-benzimidazol-2-ylacetonitrile gave 1,6-naphthyridine 5 and pyrido[1,2-a]benzimidazole 6 , respectively. Some novel pyrazolo[3,4-b]pyridine 7 , pyrido[2,3-d]pyrimidines 8 and 9 were synthesized from the ring opening ring closure reactions of carboxaldehyde 1 with certain heterocyclic enamines. In addition, reaction of carboxaldehyde 1 with certain cyclic enols produced a variety of products. Treatment of carboxaldehyde 1 with 1,3-cyclohexanediones gave xanthene-1,8-diones 19 and 20 . Reaction of carboxaldehyde 1 with 5-methyl-2,4-dihydro-3H-pyrazol-3-one proceeds in 1:2 M ratio producing pyrazolo [4′,3′:5,6]pyrano[2,3-c]pyrazole derivative 22 . Carboxaldehyde 1 reacted with certain heterocyclic compounds containing active methylene groups to give the corresponding condensation products 22 - 27 . The synthesized compounds were screened in vitro for their antimicrobial activity and showed high to moderate activities against the tested microorganisms.     

Stereoselectivity of the Radical Reductive Alkylation of Enamines: Importance of the Allylic 1,3-Strain Model

Radical addition to enamines using Bu₃SnH as reducing agent are reported (Schemes 2 and 4). The diastereoselectivity of these reactions was examined in different systems (Tables 1 and 2). Enamines derived from cyclic ketones such as cyclohexanone were alkylated with high diastereoselectivity with preferential formation of the cis-disubstituted cycloalkanes. In acyclic systems such as enamines derived from propiophenone and diethyl ketone, moderate to high stereoselectivities were observed in the H-abstraction step. A model based principally on minimization of allylic 1,3-strain (A^1,3 strain) was deduced from the experimental results and semi-empirical (AM1) calculations.     

Synthese de dihydro-6,7 benzo-b [1H] azonines par extension de cycle de dihydro-4,5 benzo-b [1H] azepines

Activated acetylnic reagents add to heterocyclic enamines 4,5-dihydro-1H-benzo[b]azepines and by electrocyclisation, give 6,7-dihydro-1H-benzo[b]azoninines. The structure of those new heterocycles is demonstrated by mass spectra, ¹H and ¹³C nmr.     

Relative tendency of carbonyl compounds to form enamines

Equilibria between carbonyl compounds and their enamines (from O-TBDPS-derived prolinol) have been examined by NMR spectroscopy in DMSO-d(6). By comparing the exchange reactions between pairs (enamine A + carbonyl B → carbonyl A + enamine B), a quite general scale of the tendency of carbonyl groups to form enamines has been established. Aldehydes quickly give enamines that are relatively more stable than those of ketones, but there are exceptions to this expected rule; for example, 1,3-dihydroxyacetone acetals or 3,5-dioxacyclohexanones (2-phenyl-1,3-dioxan-5-one and 2,2-dimethyl-1,3-dioxan-5-one) show a greater tendency to afford enamines than many α-substituted aldehydes.     

A direct retro-Reformatsky fragmentation: formal ring enlargement of cyclic ketones for novel and practical synthesis of heterocyclic enamines

A novel and practical synthesis of heterocyclic enamines has been developed from the formal ring enlargement of cyclic ketones, which comprised the retro-Reformatsky fragmentation reaction as a key step. Under alkaline bromination conditions, the Reformatsky adducts derived from five- to seven-membered cyclic ketones underwent efficiently a direct retro-Reformatsky fragmentation, followed by spontaneous alpha,alpha-dibromination, to produce alpha,alpha,omega-tribromo-beta-ketoester compounds in a one-pot reaction. Highly regioselective reduction of alpha,alpha,omega-tribromo-beta-ketoesters with Cu-Zn alloy under mild conditions afforded omega-bromo-beta-ketoesters in good to excellent yields. Treatment of omega-bromo-beta-ketoesters with sodium azide followed by intramolecular aza-Wittig reaction or catalytic hydrogenation furnished heterocyclic secondary enamines, while a straightforward cyclocondensation of omega-bromo-beta-ketoesters with amines led to the formation of heterocyclic tertiary enamines.     

Synthesis of 5-amino-1,3-dimethylpyrazol-4-yl aryl ketones

A convenient preparation of 5-amino-1,3-dialkylpyrazol-4-yl heterocyclic ketones is reported. They are prepared from the reaction of heterocyclic esters with the di-lithio derivative from N-(4-bromo-1,3-dimethyl-1H-pyrazol-5-yl)benzamide ( 1 ).     

Diastereoselective Synthesis of Cyclopenta[c]furans by a Catalytic Multicomponent Reaction

A diastereoselective three‐component reaction between alkynyl enones, aldehydes and secondary amines is reported. With the aid of a benign indium catalyst, a range of highly substituted cyclopenta[c]furan derivatives can be obtained in a single‐step procedure. The formation of the stereodefined heterocyclic motifs takes place via in situ generation of enamines followed by two sequential cyclization steps.     

The Action of Carbon Disulfide and Sulfur on Enamines,Ketimines, and CH Acids

The reaction of sulfur, carbon disulfide, and enamines at room temperature leads mainly or exclusively to 3H-1,2-dithiole-3-thiones; these are occasionally accompanied by 2H-1,3-dithiole-2-thiones, which can also be prepared by a modified procedure. Many enamines react with sulfur at room temperature to form thioamides. At about 50°C, enamines of acetophenone give 2-benzylidene-4-phenyl-2H-1,3-dithiol. The action of isothiocyanates and sulfur on enamines leads to the formation of thiazolidine-2-thiones. 2H-Thiopyran-2-thiones can be prepaAred from enamines or dienamines with carbon disulfide at room temperature. The reaction of ketimines (Schiff bases) with carbon disulfide and sulfur yields 3H-1,2-dithiole-3-thiones or isothiazoline-5-thiones. The reaction of alkynes with sulfur and carbon disulfide leads to 2H-1,3-dithiole-2-thiones. Nitriles containing active methylene groups react with carbon disulfide and sulfur to form 5-amino-3H-1,2-dithiole-3-thiones. When isothiocyanates are used instead of CS₂, the reaction leads to δ⁴-4-amino-thiazoline-2-thiones.     

几个烯胺的邻硝基苯甲酰化和在酸水解中发生的重排

为了了解芳酰基化的效率和双酰基衍生物的形成, 对几个典型醛和酮的吗啉烯胺进行了邻硝基苯甲酰化的探索。丁醛和异丁醛吗啉烯胺的酰化正常, 水解分别生成55%的2-(邻硝基苯甲酰基)丁醛(2)和40%的2-(邻硝基苯甲酰基)异丁醛(3)。3-戊酮和1, 3-二甲氧基丙酮的吗啉烯胺在酰化和水解时分别生成37%和14.8%相应的β-二酮的烯醇邻硝基苯甲酸酯(4)和(5)。4和5的酸水解发生意外的1, 5-和1,3-酰基转位, 分别生成3, 5-二甲基-2, 6-双(邻硝基苯基)吡喃-4-酮(6)和2-甲氧基-2-甲氧乙酰基-1, 3-双(邻硝基苯基)-1, 3-丙二酮(7)。环戊酮和环已酮吗啉烯胺的酰化分别产生9%和34%的双酰基烯胺(9a)和(9b),逐次酸水解得到2-(邻硝基苯甲酰基)环戊酮(11a)和-环已酮(11b)。在总酰化产物的直接水解中, 11a的产率可以达到81%, 而11b只有35%。对双酰化进行了一些讨论。     

Reaction of unsymmetrical trifluoromethyl-containing 1,3-dicarbonyl compounds with ‘push-pull’ enamines

The reaction of ‘push-pull’ enamines with trifluoromethyl-containing 1,3-dicarbonyl compounds was investigated. It was found that the reaction is sensitive both to the structure of the enamines and to reaction conditions. As a result, a set of various trifluoromethyldialkylanilines was obtained.     

Quantification of the Electrophilicities of Diazoalkanes: Kinetics and Mechanism of Azo Couplings with Enamines and Sulfonium Ylides

Kinetics and mechanism of the reactions of methyl diazoacetate, dimethyl diazomalonate, 4-nitrophenyldiazomethane, and diphenyldiazomethane with sulfonium ylides and enamines were investigated by UV-Vis and NMR spectroscopy. Ordinary alkenes undergo 1,3-dipolar cycloadditions with these diazo compounds. In contrast, sulfonium ylides and enamines attack at the terminal nitrogen of the diazo alkanes to give zwitterions, which undergo various subsequent reactions. As only one new bond is formed in the rate-determining step of these reactions, the correlation lg k₂(20 °C)=s_N(N+E) could be used to determine the one-bond electrophilicities E of the diazo compounds from the measured second-order rate constants and the known reactivity indices N and s_N of the sulfonium ylides and enamines. The resulting electrophilicity parameters (−21<E<−18), which are 11–14 orders of magnitude smaller than that of the benzenediazonium ion, are used to define the scope of one-bond nucleophiles which may react with these diazoalkanes.     

N‐functionalized azolin‐2‐ylidene‐palladium‐catalyzed heck reaction

Novel 1,3‐dialkylimidazolidinium, 1,3‐dialkyl‐3,4,5,6‐tetrahydropyrimidinium, and 1,3‐dialkyl‐1H‐4,5,6,7‐tetrahydrodiazepinium hexafluorophosphates ( 1a–c, 2a–c ) as N‐heterocyclic carbene precursors have been synthesized and characterized. The incorporation of saturated N‐heterocyclic carbenes into palladium precatalysts gives high‐catalyst activity in the Heck coupling of aryl bromide substrates in aqueous media. The complexes were generated in the presence of Pd(OAc)₂ by in situ deprotonation of 1,3‐dialkylazolinium salts 1, 2 . © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:82–86, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20415     

Reaction of sulfene with heterocyclic α-dialkylaminomethyleneketones II. Synthesis of 5N-1,2-oxathiino[5,6-c] [1]benzopyran derivatives

The reaction of sulfene with 3-dialkylaminomethylene-4-chromanone and 3-dialkylamino-methylene-6-methyl-4-ehromanone gave 1,4-cycloadducts which are derivatives of a new heterocyclic system, i.e., 5H-1,2-oxathiino[5,6-c][1]benzopyran. The structures of the adductswere determined by ir and nmr spectral data. Two new α-hydroxymethyleneketones (3-hydroxy-methylene-4-chromanone and its 6-methyl analogue) as well as some of their derived enamines were prepared. During the preparation of N,N-diethylenamines a self-condensation occurs, which gives the byproducts Xa-b.     

Cycloadditions of isoquinolinium N-arylimides to enamines

The azomethine imine group of isoquinolinium N-arylimides 2 is partially incorporated into an aromatic ring. The nucleophilic-electrophilic 1,3-dipoles 2 undergo cycloadditions to ethylene derivatives bearing either electron-withdrawing or electron-releasing substituents. The regiochemistry is bidirectional; electron-attracting substituents appear at the 1-position of the tricyclic adducts. Various enamines, however, adopt an orientation such that the amino function appears at the 2-position. The tricyclic adducts undergo an acid-catalyzed hyrazo rearrangement.     

Synthesis of Substituted 2‐Amino‐1,3‐oxazoles via Copper‐Catalyzed Oxidative Cyclization of Enamines and N,N‐Dialkyl Formamides

A facile synthesis of 2‐amino‐1,3‐oxazoles via Cu^I‐catalyzed oxidative cyclization of enamines and N ,N ‐dialkyl formamides has been developed. The reaction proceeds through an oxidative C−N bond formation, followed by an intramolecular C(sp²)−H bond functionalization/C−O cyclization in one pot. This protocol provides direct access to useful 2‐amino‐1,3‐oxazoles and features protecting‐group‐free nitrogen sources, readily available starting materials, a broad substrate scope and mild reaction conditions.     

Ring-chain tautomerism in organic synthesis: synthesis of heterocyclic enamines from a novel and practical formal ring transformation reaction of lactones

A novel approach to heterocyclic enamines has been developed from the formal ring transformation reaction of lactones. The synthesis comprises consecutive Reformatsky reaction of lactones and mesylation of the resulting mixture of ring-chain tautomers in a one-pot reaction, followed by cyclocondensation reaction with primary amines. The synthetic application of this method was demonstrated by a straightforward preparation of indolizidine compounds via N-(3-bromopropyl)-substituted enamine intermediates. The use of cheap and readily available materials and reagents under very mild conditions renders this formal ring transformation method practical and applicable in the preparation of various heterocyclic enamines that are the precursors for (poly)hydroxylated alkaloid derivatives.     

Condensation of 1,3-diketones with 1,8-diaminonaphthalene: Synthesis ofbis(2,3-dihydroperimidine-2-spiro)cycloalkanes

Summary Cyclic 1,3-diketones like cyclopentane-1,3-dione, cyclohexane-1,3-dione, and 5,5-dimethylcyclohexane-1,3-dione react with 1,8-diaminonaphthalene to afford new condensed heterocyclic spiro systems.

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Kondensation von 1,3-Diketonen mit 1,8-Diaminonaphthalin: Synthese vonBis(2,3-dihydroperimidin-2-spiro)cycloalkanen

Zusammenfassung Cyclische 1,3-Diketone wie Cyclopentan-1,3-dion, Cyclohexan-1,3-dion und 5,5-Dimethylcyclohexan-1,3-dion reagieren mit 1,8-Diaminonaphthalin zu neuen kondensierten heterocyclischen Spiranen.