ABSTRACT
A new perspective on the reactivity of hydroxyquinones was revealed as an acetal derivative of lawsone was synthesized, isolated, and used in tandem Knoevenagel/hetero-Diels-Alder reactions catalyzed by S-proline. The intermediate alkylidene-1,3-diones that were formed in situ reacted with electron rich alkenes to predominantly afford pyrano-1,2-naphthoquinone (ß-lapachone) derivatives along with the isomeric pyrano-1,4-naphthoquinone (α-lapachone) derivatives in high to excellent total yields. Interestingly, the highly reactive arylidene-1,3-dione derivatives were found to be stable and isolable. DFT calculations suggest that these hetero-Diels-Alder reactions have a high polar character, taking place through a two-stage one-step mechanism. An analysis of the conceptual DFT indices allows explaining the remarkable site-selectivity observed.
ABSTRACT
Thermal decomposition of the phenyliodonium ylide of lawsone gives rise to a highly reactive cyclic α,α'-dioxoketene, indanedioneketene, which reacts with electron-rich dienophiles such as enol ethers to afford [4 + 2] cycloadducts. The initially formed 2,3-dihydro-2-alkoxy-indeno[1,2-b]pyrano-4,5-diones are labile compounds since through an opening of the pyranone ring upon heating they easily tautomerize to alkoxyallylidene-indenedione derivatives and under acid-catalysis they are additionally transformed to 2-(1,3-dihydroxyallylidene)-1H-indene-1,3(2H)-dione or by loss of alcohol to indeno[1,2-b]pyran-4,5-diones. A DFT study explains the polar nature of the cycloaddition reaction, the observed reactivity and suggests a possible mechanism operating in these reactions.
ABSTRACT
Indanedioneketene, a compound resulting from the thermal degradation of the phenyliodonium ylide of lawsone, dimerizes quantitatively to a spiro-oxetanone derivative, a key compound for further transformations. A theoretical electronic structure study of this unusual for alpha-oxoketenes [2 + 2] cyclization reaction both in the gas phase (DFT, MP2) and in dichloromethane solution (DFT), provides support for (a) a single-step, transition-state (involving a four-membered cyclic ring) charge-controlled, concerted mechanism and (b) a [4 + 2] cyclization reaction, not observed but studied theoretically in this study. A parallel study of an open-chain alpha,alpha'-dioxoketene dimerization explains the difference in the stability and reactivity observed experimentally between the cyclic and open-chain products.
Subject(s)
Computer Simulation , Indans/chemistry , Ketones/chemistry , Lactones/chemical synthesis , Spiro Compounds/chemical synthesis , Cyclization , Dimerization , Lactones/chemistry , Molecular Structure , Spiro Compounds/chemistryABSTRACT
Indenocarboxamides, resulting from the sequential addition of two arylamine equivalents to indanedione ketene dimer, are oxidized by [bis(trifluoroacetoxy)iodobenzene] to fused indeno-1,4-diazepinones in yields depending on the substituents on both aromatic rings. A plausible reaction pathway explaining the formation of the title compounds, as well as the formation of the two other minor products of the reaction, through a common intermediate, is suggested.
Subject(s)
Azepines/chemistry , Indenes/chemistry , Iodobenzenes/chemistry , Amides/chemical synthesis , Amides/chemistry , Amines/chemistry , Cyclization , Molecular Structure , Oxidation-Reduction , StereoisomerismABSTRACT
Although 1,3-dioxoindane-2-carboxylic acid is highly unstable, its enamino derivatives can be isolated by careful hydrolysis of their esters with 2,4-dihydroxy-1,4-naphthoquinone. Crystal structure determination reveals the formation of two intramolecular hydrogen bonds, offering thus a possible explanation for the stability of these acids.
Subject(s)
Amines/chemistry , Carboxylic Acids/chemistry , Indans/chemistry , Crystallography, X-Ray , Hydrogen Bonding , Molecular StructureSubject(s)
Antineoplastic Agents/pharmacology , Cell Membrane Permeability/drug effects , Cell Proliferation/drug effects , Indenes/pharmacology , Protein Kinase Inhibitors/pharmacology , Pyrimidines/pharmacology , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Umbilical Cord/drug effects , Adenosine Triphosphate/metabolism , Antineoplastic Agents/chemical synthesis , Cell Membrane Permeability/physiology , Cells, Cultured , Humans , Inhibitory Concentration 50 , Protein Kinase Inhibitors/chemical synthesis , Spectrum Analysis , Umbilical Cord/cytology , Umbilical Cord/metabolismABSTRACT
The highly reactive indanedioneketene 5, resulting from the thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone, 4), in the absence of nucleophiles dimerizes to the corresponding tetraoxo spiro oxetanone 6 in quantitative yield. This oxetanone exhibits an interesting reactivity toward amines.
Subject(s)
Amines/chemistry , Indans/chemistry , Ketones/chemistry , Crystallography, X-Ray , Dimerization , Hydrogen Bonding , Models, Molecular , Molecular Structure , Naphthoquinones/chemical synthesis , Naphthoquinones/chemistry , Stereoisomerism , TemperatureABSTRACT
[reaction: see text] Thermal decomposition of phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone (lawsone) in the presence of indole derivatives affords 3-acylated indoles existing in their enol forms, through a ring contraction and alpha,alpha'-dioxoketene formation reaction. The same reactants afford 3-(3-indolyl)-2-hydroxy-1,4-naphthoquinones in a copper-catalyzed reaction. Enamines, among other C-nucleophiles tested, give analogous results.
Subject(s)
Indoles/chemistry , Naphthoquinones/chemistry , Onium Compounds/chemistry , Molecular Structure , Onium Compounds/chemical synthesisABSTRACT
The phenyliodonium ylide of 2-hydroxy-1,4-naphthoquinone reacts with aminoesters, ureas, aminoalcohols and aminophenols in refluxing dichloromethane to afford good yields of indanedione 2-carboxamido compounds, that in solution exist in an enol-amide form. The same reactants in a copper-catalyzed reaction afford mainly the corresponding N-arylo compounds. Arylhydrazines are mainly oxidized by the ylide and arylation occurs only in a low yield.
Subject(s)
Amines/chemistry , Heterocyclic Compounds/chemical synthesis , Naphthoquinones/chemistry , Onium Compounds/chemistry , Catalysis , Models, BiologicalABSTRACT
Aryliodonium ylides of 2-hydroxy-1,4-naphthoquinone react with amines in refluxing dichloromethane to afford good yields of indanedione 2-carboxamides 5, through a ring-contraction and alpha,alpha'-dioxoketene formation reaction. These amides exist in solution in an unusual enol-amide form. In contrast, the same reactants in a copper-catalyzed reaction afford arylamines and 3-iodo-4-hydroxy-1,2-naphthoquinone.