Quinone Monoketals Research Articles

ZnCl2-Promoted Three-Component Reaction of 2-Aminochromenones, Aromatic Aldehydes, and Quinone Monoketals: Access to 5,6-Dihydro-12H-chromeno[2,3-c]isoquinolin-12-one Derivatives.

A three-component reaction of 2-amino-4H-chromen-4-ones, aromatic aldehydes, and 4,4-dialkoxycyclohexa-2,5-dien-1-ones for the concise synthesis of chromeno[2,3-c]dihydroisoquinoline derivatives has been investigated. This reaction involved consecutive ZnCl2-promoted Micheal addition and intramolecular Friedel-Crafts alkylation. This synthetic protocol offered several advantages, including the readily accessible starting materials, good functional group tolerance, and simplicity of operation. Additionally, the structures of products obtained were determined based on X-ray diffraction studies.

Study of the Oxidative Cleavage Proposed in the Biogenesis of Transtaganolides/Basiliolides: Pyran‐2‐one Aromaticity‐Mediated Regioselective Control and Biogenetic Implications

The synthetic feasibility of the oxidative cleavage: epoxidation of 7‐O‐geranylscopoletin followed by electrocyclic ring‐opening, proposed in the biogenesis of transtaganolides/basiliolides is studied. Unlike the proposed pericyclic reactions, this pathway has not yet been addressed. Three synthetic strategies have been tested consisting of: i) Baeyer–Villiger oxidation of p‐quinoids, ii) hydrolysis of quinone monoketals, or iii) direct fragmentation by using oxygen donors. Oxidation of the benzene ring of hydroxylated coumarins has been achieved using peroxyacids, but cleavage took place between undesired positions. The aromaticity conservation of the pyran‐2‐one cycle during oxidation is the controlling factor of these observed regioselectivities. The use of a 4,5‐dihydroxy‐2‐methoxycinnamate model, in which the pyran‐2‐one ring does not exert influence on oxidation, has allowed the design of a synthetic sequence toward an analogue of the natural pyran‐2‐one isolated from Thapsia transtagana, key in the biogenesis. Mechanistic proposals for the obtained results as well as their biogenetic implications are raised.

Palladium-Catalyzed Asymmetric 1,4-Addition of Diarylphosphines to Quinone Monoketals

Palladium-Catalyzed Asymmetric 1,4-Addition of Diarylphosphines to Quinone Monoketals

Organocatalytic, regioselective allylic- and 1,6-substitution of quinone monoketals with diaryl H-phosphine oxides

An efficient selective synthesis of C- and O-phosphoryl-substituted phenols from easily available diaryl H-phosphine oxides with quinone monoketals (QMAs) has been developed. With the assistance of opponent characteristic additives (e.g., H2O and Et3N), diaryl H-phosphine oxides could selectively proceed the allylic- and 1,6-substitution to conjugate with the C-/O- positions of QMAs. The reported protocol is green and practical, and represents an efficient method to functionalize C-/O-phosphoryl-substituted phenols with moderate to good yields.

Studies toward the Total Synthesis of Nogalamycin: Construction of the Complete ABCDEF-Ring System via a Convergent Hauser Annulation.

The convergent synthesis of the complete ABCDEF-ring system within nogalamycin, an anthracycline natural product, was studied. The pivotal Hauser annulation for the anthraquinone core construction was achieved by the fusion of two highly functionalized segments: a cyanophthalide (the AB-ring segment) and a tricyclic quinone monoketal (the DEF-ring segment). Key transformations toward the AB-ring segment include an enantioselective enolate α-hydroxylation, a diastereoselective hydroboration-oxidation, and a directed aromatic lithiation-formylation. To prepare the DEF-ring segment for annulation, a mild dearomatization of the F-ring phenol group by (diacetoxyiodo)benzene (PIDA) was employed.

Site-Selective Reaction of Enaminones and Enamine Esters for the Synthesis of Novel Diverse Morphan Derivatives.

An efficient and concise protocol was developed for the synthesis of diverse morphan derivatives 5–7 by the Michael and aza-Michael reaction of different types of quinone monoketals 1 or quinone imine ketals 2 with enaminones or enamine esters 3 promoted by 1,8-diazabicyclo[5.4.0]undec-7-ene in acetone at reflux. Notably, when cyclic enaminone 4 was used as a substrate in the aza-Michael and 1,2-addition reactions with quinone monoketals 1, they gave another novel morphan 8. This method is suitable for parallel synthesis of bridged ring compounds. As a result, highly diverse morphan derivatives were easily and efficiently prepared by the Michael/aza-Michael or aza-Michael/1,2-addition reactions.

Diastereoselective Synthesis of Morphan Derivatives by Michael and Hetero-Michael Addition of 1,1-Enediamines to Quinone Monoketals

A general and concise method was developed for the synthesis of highly functionalized morphans 3–4 by the Michael and hetero-Michael addition reaction of different types of quinone monoketals 1 and 1,1-enediamines 2 in ethanol or 1,4-dioxane at reflux. This method is suitable for the efficient parallel syntheses of N-containing heterocycles. A library of highly functional morphan derivatives was easily constructed using the Michael/hetero-Michael reaction.

An environmentally benign double Michael addition reaction of heterocyclic ketene aminals with quinone monoketals for diastereoselective synthesis of highly functionalized morphan derivatives in water

This effort involved an efficient and concise one-pot procedure for the synthesis of morphans based on quinone monoketals 1 reacting with HKAs 2.

ChemInform Abstract: [3 + 2]‐Annulations of N‐Alkyl‐3‐Substituted Indoles with Quinone Monoketals Catalyzed by Broensted Acids.

AbstractA novel method is elaborated for the synthesis of benzofuro[2,3‐b]indolines (III) and (V) by [3 + 2]‐annulation of N‐alkyl‐3‐substituted indoles with quinone monoketals (II) in the presence of (‐)‐CSA as catalyst.

3 + 2]-Annulations of N-alkyl-3-substituted indoles with quinone monoketals catalysed by Brønsted acids

An organocatalytic dearomative [3 + 2]-annulation of N-alkyl-3-alkylindoles with quinone monoketals is developed. The reaction provides a mild and straightforward way to various benzofuro[2,3-b]indolines of potential biological and pharmaceutical interest in moderate to good yields. Moreover, when 3-phenylindole, a problematic substrate in previous relevant studies, was used as the substrate under the otherwise same reaction conditions, a novel 1,2-shift of the phenyl group occurred followed by aromatization to provide 2,3-diaryl indoles useful for cancer therapy studies in moderate yields.

Synthesis of o-chlorophenols via an unexpected nucleophilic chlorination of quinone monoketals mediated by N,N′-dimethylhydrazine dihydrochloride

An unexpected nucleophilic chlorination of a quinone monoketal while carrying out a pyrazolidine synthesis has led to a general preparation of multisubstituted phenols. The products are obtained in good to high yields under mild conditions. The bridged pyrazolidines that were the original targets are obtained in the presence of a protic solvent.

ChemInform Abstract: Double Hetero‐Michael Addition of N‐Substituted Hydroxylamines to Quinone Monoketals: Synthesis of Bridged Isoxazolidines.

AbstractQuinone monoketals (I) give bridged isoxazolidines in high yields, whereas significantly lower yields are obtained by using substituted substrates (IV).

Double Hetero-Michael Addition of N-Substituted Hydroxylamines to Quinone Monoketals: Synthesis of Bridged Isoxazolidines

A general synthesis of bridged isoxazolidines from a double hetero-Michael addition of N-substituted hydroxylamines to quinone monoketals has been developed. The different addition order of N-benzylhydroxylamine and N-Boc hydroxylamine is also discussed. Moreover, the various functionalities in the isoxazolidine products allow facile derivatization.

ChemInform Abstract: A Variation of the Fischer Indolization Involving Condensation of Quinone Monoketals and Aliphatic Hydrazines.

The indole ring system is one of the most ubiquitous heterocycles in nature. Many indole-containing natural products show a wide scope of biological activities, in particular because they bind to many receptors with high affinity. Since Baeyer s first synthesis of indole from oxindole in 1866 (indigo!isatin!oxindole!indole), numerous methods for the synthesis of indoles have been reported. One of the most efficient and widely employed syntheses is the Fischer indolization discovered in 1883. Compared with other indole syntheses, the importance of Fischer indolization lies in its simplicity and convenience, that is, formation of a critical C C bond to an unactivated aromatic carbon through a [3,3] sigmatropic rearrangement of enolizable Narylhydrazones. After more than a century of development, the Fischer indole synthesis remains a reliable and versatile method for the preparation of a variety of indole natural products and medicinal compounds. Many new variations have been developed in recent years. Most recently, the first catalytic asymmetric version of Fischer indole synthesis was reported by the group of List. Although the Fischer indole synthesis is widely used, several disadvantages still remain. The classical Fischer indole synthesis starts with arylhydrazines, which are generally made either from anilines through diazonium salts, or from aryl halides through transitionmetal-mediated coupling reactions. These processes involve the use of aniline precursors and toxic reagents (nitrous acid, stannous chloride, etc.) and potentially explosive diazonium intermediates, or expensive transition metals. We report herein a novel variation of the Fischer indolization involving a one-pot condensation of quinone monoketals with aliphatic hydrazines (Scheme 1). To the best of our knowledge, this is the first Fischer-type indole synthesis using an aliphatic hydrazine as the nitrogen source and a quinone monoketal as a masked benzene ring. We envisioned that condensation of quinone monoketal 1 and aliphatic hydrazine 2 would ultimately lead to an indole via alkylaryldiazene 5 and arylhydrazone intermediate 6, as illustrated in Scheme 2. The feasibility of this method relies on the initial formation of alkylaryldiazene 5 from a 1,2addition/dehydration sequence. It should be noted that there has been no report on the synthesis of alkylaryldiazenes 5 from quinone derivatives and aliphatic hydrazines, although arylaryldiazenes (azobenzenes) have been synthesized from condensations of arylhydrazines with quinones, quinols, quinone monoketals, and quinone bisketals. There is a single report on the condensation of an aliphatic hydrazine (N,N-dimethylhydrazine) with naphthoquinone monoketal, which, however, gave a 1,4-addition product in high yield. Therefore, our first object was to test the practicality of the Scheme 1. Strategies for the synthesis of indoles.

A Variation of the Fischer Indolization Involving Condensation of Quinone Monoketals and Aliphatic Hydrazines

The indole ring system is one of the most ubiquitous heterocycles in nature. Many indole-containing natural products show a wide scope of biological activities, in particular because they bind to many receptors with high affinity. Since Baeyer s first synthesis of indole from oxindole in 1866 (indigo!isatin!oxindole!indole), numerous methods for the synthesis of indoles have been reported. One of the most efficient and widely employed syntheses is the Fischer indolization discovered in 1883. Compared with other indole syntheses, the importance of Fischer indolization lies in its simplicity and convenience, that is, formation of a critical C C bond to an unactivated aromatic carbon through a [3,3] sigmatropic rearrangement of enolizable Narylhydrazones. After more than a century of development, the Fischer indole synthesis remains a reliable and versatile method for the preparation of a variety of indole natural products and medicinal compounds. Many new variations have been developed in recent years. Most recently, the first catalytic asymmetric version of Fischer indole synthesis was reported by the group of List. Although the Fischer indole synthesis is widely used, several disadvantages still remain. The classical Fischer indole synthesis starts with arylhydrazines, which are generally made either from anilines through diazonium salts, or from aryl halides through transitionmetal-mediated coupling reactions. These processes involve the use of aniline precursors and toxic reagents (nitrous acid, stannous chloride, etc.) and potentially explosive diazonium intermediates, or expensive transition metals. We report herein a novel variation of the Fischer indolization involving a one-pot condensation of quinone monoketals with aliphatic hydrazines (Scheme 1). To the best of our knowledge, this is the first Fischer-type indole synthesis using an aliphatic hydrazine as the nitrogen source and a quinone monoketal as a masked benzene ring. We envisioned that condensation of quinone monoketal 1 and aliphatic hydrazine 2 would ultimately lead to an indole via alkylaryldiazene 5 and arylhydrazone intermediate 6, as illustrated in Scheme 2. The feasibility of this method relies on the initial formation of alkylaryldiazene 5 from a 1,2addition/dehydration sequence. It should be noted that there has been no report on the synthesis of alkylaryldiazenes 5 from quinone derivatives and aliphatic hydrazines, although arylaryldiazenes (azobenzenes) have been synthesized from condensations of arylhydrazines with quinones, quinols, quinone monoketals, and quinone bisketals. There is a single report on the condensation of an aliphatic hydrazine (N,N-dimethylhydrazine) with naphthoquinone monoketal, which, however, gave a 1,4-addition product in high yield. Therefore, our first object was to test the practicality of the Scheme 1. Strategies for the synthesis of indoles.

A Variation of the Fischer Indolization Involving Condensation of Quinone Monoketals and Aliphatic Hydrazines

Neuer Dreh: Ohne salpetrige Säure, ohne Diazoniumion und ohne Übergangsmetall kommt die hier vorgestellte Variante der Fischer-Indolsynthese aus. Die Kondensation von Chinonmonoketalen mit aliphatischen Hydrazinhydrochloriden liefert Indole über Alkylaryldiazen-Intermediate. Diese Ergänzung der klassischen Fischer-Synthese macht Indole in zwei Stufen aus breit verfügbaren Phenolen unter milden Bedingungen zugänglich. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Rapid entry to functionally rich bicyclo[4.1.0]heptenone systems

A facile process for the synthesis of highly substituted bicyclo[4.1.0]heptenones via Corey–Chaykovsky reaction of quinone monoketals is presented. The obtained products were employed to functionalize 3-position of indoles providing compounds which might have potential use in medicinal chemistry.

Tin Tetrachloride‐Catalyzed Regiospecific Allylic Substitution of Quinone Monoketals: An Easy Entry to Benzofurans and Coumestans

AbstractA highly regioselective allylic substitution of quinone monoketals with α‐oxoketene dithioacetals is achieved under the catalysis of only tin tetrachloride (1 mol%). The advantages of the reaction, including its simplicity, rapidity, low catalyst loading of inexpensive tin tetrachloride, mild conditions and; in particular, the regiospecificity, is proposed to be due to a pseudo‐intramolecular process. This new synthetic method provides a facile [3+2] cycloaddition route to benzofurans and is highlighted by the synthesis of coumestans.

ChemInform Abstract: Conjugate Reduction of Quinone Derivatives. A Route to Phenol Keto- Tautomer Equivalents.

Abstract 1,4-addition of hydride to quinone monoketals 1 and p -quinol ethers 2, mediated by bis-(2,6-di- t -butyl-4-methylphenoxy)-methylaluminum (MAD), affords 4,4-substituted-2-cyclohexen-1-ones 3, which represent keto-tautomer equivalents of phenols.

Double Conjugate Addition of a Nitropropionate Ester to a Quinone Monoketal: Synthesis of an Advanced Intermediate to (±)-Gelsemine

A double conjugate addition between the lithium dianion of ethyl 3-nitropropionate and p-benzoquinone dimethyl ketal afforded a mixture of diastereomeric [3.2.1]bicylooctanones. These products were converted into an advanced intermediate previously carried forward to (+/-)-gelsemine by Fukuyama and Liu.