Showing papers by "Otohiko Tsuge published in 1987"

Simple generation of nonstabilized azomethine ylides through decarboxylative condensation of α-amino acids with carbonyl compounds via 5-oxazolidinone intermediates

Abstract: Heating α-amino acids with a variety of carbonyl compounds generates N-unsubstituted or N-substituted azomethine ylides of nonstabilized types through the elimination of water and carbon dioxide. The ylides are captured by olefinic, acetylenic, and carbonyl dipolarophiles producing pyrrolidines, pyrrolines, and oxazolidines. The reaction involves intermediary 5-oxazolidinones which can be sometimes isolated. Some synthetic equivalents of parent azomethine ylide, methaniminium methylide, are accessible by this route.

Regioselective cycloadditions of N-protonated azomethine ylides and 2-azaallyl anions generated from N-(silylmethyl) thioimidates, synthetic equivalents of nonstabilized nitrile ylides

Abstract: Cycloadditions dipolaires 1,3 des ylures obtenus par desilylation en presence d'eau de N-trimethylsilylmethyl thiocarboximidates(A); additions des carbanions obtenus par desilylation directe des composes A ou du S,S-dimethyl N-trimethylsilylmethyl dithiocarbonimidate avec des composes ethyleniques ou des composes carbonyles

Simple Generation of Ester-Stabilized Azomethine Ylides from 2-Amino Esters and Carbonyl Compounds. Stereochemistry of Their Cycloadditions

Abstract: Condensation of 2-amino esters with carbonyl compounds leads to simple generation of ester-stabilized azomethine ylides which are trapped by olefinic dipolarophiles as cycloadducts Anti ylides are exclusively involved in the cycloadditions when N-substituted 2-amino esters are employed for the ylide generation, while syn ylides from N-unsubstituted 2-amino esters Relative stability among all possible ylide isomers has been inspected and the selective involvement of particular ylidic forms has been explained on the ground of 1,5-dipole interaction or hydrogen bonding stabilization Endo- and exo-selectivity of the cycloadditions is also discussed

Synthesis of (diethoxyphosphoryl) acetonitrile oxide and its cycloaddition to olefins. Synthetic applications to 3,5-disubstituted 2-isoxazolines

Abstract: (Diethoxyphosphoryl)acetonitrile oxide undergoes regioselective cycloaddition to olefins leading to 3-[(diethoxyphosphoryl)methyl]-2-isoxazolines or -isoxazole. The phosphorus-stabilized carbanions generated by deprotonation of the cycloadducts can be utilized for the condensation with carbonyl compounds, alkylation, and oxidation with oxygen to provide 3,5-disubstituted 2-isoxazolines as useful synthetic building blocks. Raney nickel hydrogenolysis of 3-[(diethoxyphosphoryl)methyl]-2-isoxazolines gives β-hydroxy-β′-phosphoryl ketones bearing a variety of functional groups, which can be further converted into α,β-unsaturated β′-phosphoryl ketones.

Reactions of 1,4-bis(trimethylsilyl)-1,4-dihydropyridines with carbonyl compounds : A new method for regioselective synthesis of 3-alkylpyridines.

Abstract: A new method for the alkyl group introduction at the 3-position of pyridienes is described: Reductive disilylation of pyridine, its 2-methyl, 3-methyl, and 4-methyl derivatives affords the corresponding 1,4-disilyl-1,4-dihydropyridines. In the presence of a catalytic amount of tetrabutylammonium fluoride, these dihydropyridines smoothly react with a variety of aldehydes and ketones to give 3-alkylpyridines.

Synthesis of Arylthio-Substituted 3,8-Diphenyl-1,2-diazacycloocta-2,4,6,8-tetraenes and Their Thermolysis

Abstract: Nucleophilic substitution of 4,7-dichloro-3,8-diphenyl-1,2-diazocine with succinimide, phthalimide, N-methyl-p-toluenesulfonamide, and o-benzosulfimide, in the presence of silver oxide, gave the corresponding 4-mono(imido)- and 4,7-di(imido)-1,2-diazocines. 4-Acetoxy-7-phthalimido- and 4-phenylthio-7-phthalimido-1,2-diazocine were also prepared. Thermolysis of the mono(imido)-1,2-diazocines in xylene under reflux afforded the corresponding di(imido)-1,2-diazocine and/or five pyridine derivatives, whose relative yields depended upon the nature of imido substitutents in the diazocines. However, 4,7-di(imido)-1,2-diazocines did not decompose in xylene under reflux. Thermolysis of 4,7-bis(phthalimido)-1,2-diazocine at 300–310 °C gave 3,6-bis(phthalimido)-2-phenylpyridine with the extrusion of benzonitrile. In the thermolysis of the acetoxy(230–240 °C) or phenylthio-substituted 1,2-diazocine (240–260 °C), 6-acetoxy- and 6-benzoyl-3-phthalimido-2-phenylpyridine, or 6(and 3)-phenylthio-3(and 6)-phthalimido-2-phe...

Cycloaddition of pyridinium methylides with electron-deficient olefins and silica-gel mediated elimination of pyridines from the cycloadducts : A new method of alkylation or hydroalkylidenation of olefins.

Abstract: Pyridinium methylides bearing an anion-stabilizing substituent at the ylide carbon react with a variety of olefins carrying two electron-withdrawing groups at the both carbons such as N-substituted maleimides, a citraconimide, dimethyl maleate, dimethyl fumarate, and 1,2-dibenzoylethene. The cycloadducts thus formed undergo a ready elimination of pyridines when treated with silica gel. This sequence is a new method for alkylation or hydroalkylidenation of olefins.

Synthesis of 5,8-Dihydroxy-2-methoxy-1,4-naphthoquinone Derivatives. A Major Naphthoquinone Moiety of Some of Naphthoquinone Antibiotics

Abstract: 6-Formyl- and 6-hydroxymethyl-5,8-dihydroxy-2-methoxy-1,4-naphthoquinones were, respectively, prepared from 2-formyl- and 2-hydroxymethyl-1,4,5,6,8-pentamethoxynaphthalenes which were synthesized as key intermediates of the new antibiotics containing 2-methoxynaphthazarin structure.

Metallic Base-Induced Cycloadditions of N-(1-Cyanoalkyl)imines via N-Metalated Azomethine Ylides: Enhanced Reactivity and High Regio- and Stereoselectivity

Abstract: Lithiation of N-(1-cyanoalkyl)imines with LDA generates new N-lithiated azomethine ylide 1,3-dipoles which show enhanced reactivity toward dipolarophiles. They undergo exclusively regio- and stereoselective 3+2 cycloaddition reaction with α,β-unsaturated esters to give 1-pyrrolines after the elimination of LiCN. Metallic bases other than LDA can be also effective. Such high regio- and stereoselectivity is explained by the involvement of N-metalated azomethine ylides.

Michael Addition and Alkylation of 2-Azaallyl Anions Derived from N-(1-Cyanoalkyl)imines, and Stereoselective Cyclization of Imine Esters or Ketones Leading to 1-Pyrrolines

Abstract: The 2-azaallyl anions derived from N-(1-cyanoalkyl)imines and DBU undergo Michael addition or alkylation to produce N-(1-alkylated 1-cyanoalkyl)imines. The Michael addition of some aryl-substituted imines are highly diastereoselective. The alkylated Michael adducts are converted into lactams through a hydrolysis and recyclization sequence. Base-induced cyclization furnishes 1-pyrrolines through a cyclization and HCN elimination sequence. In the latter reaction, 4,5-cis-1-pyrrolines are selectively produced when the adducts are treated with LDA in the presence of lithium iodide.

Photoadducts of 4,6-Dimethyl- and 4-Methoxy-6-methyl-2-pyrones with Chloroethylenes and Their Dehydrochlorination

Abstract: Sensitized photoreactions of 2-pyrones with chloroethylenes gave two kinds of [2+2]cycloadducts, 2-oxabicyclo[4.2.0]oct-4-en-3-ones (4, 8) and across the C3–C4 double bond in 2-pyrone, benzene derivatives, and/or cyclobutanecarboxylic acids: Their relative yields greatly depended upon the nature of the reactants. The dehydrochlorination of the cycloadducts 4 and 8 across the C5–C6 double bonds in the pyrones with triethylamine in ethanol gave 5-ethenyl-2-pyrones, whose structures were previously incorrectly assigned as oxocinones, via a symmetry-allowed ring opening of 2-oxabicyclo[4.2.0]octa-4,6-dien-3-ones. Some 5-ethenyl-2-pyrones possessing a chlorinated ethenyl group finally affords 5-ethynyl-2-pyrones by an anti-elimination of hydrogen chloride. The X-ray crystallographic analyses of 5-ethenyl- and 5-ethynyl-2-pyrones are also described.

Horner–Emmons Olefination of 4-Hydroxy-2-oxoalkylphosphonates and Related Compounds: Applications to the Syntheses of (±)-Gingerol, (±)-Yashabushiketol, and (±)-Dihydroyashabushiketol

Abstract: Horner–Emmons olefination of 4-hydroxy-2-oxoalkylphosphonates, readily available by hydrogenation of 5-substituted 3-phosphinylmethyl-2-isoxazolines, gives mainly E-isomers of 1-hydroxy-4-alken-3-ones bearing a variety of substituents at the 1-position. Use of the combination of triethylamine (or DBU)+lithium bromide as a weak base on the O-unprotected phosphonates is favored. Similar olefinations on the isoxazolines, 2-oxo-3-alkenylphosphonates, and 4-alkoxy-2-oxoalkylphosphonates have been also examined. Their synthetic applications to (±)-Gingerol, (±)-Yashabushiketol, and (±)-Dihydroyashabushiketol are described.

Synthesis of Hexahydroindenones through a Diels–Alder Cycloaddition and Nazarov Cyclization Sequence of Triene Alcohols

Abstract: The Diels–Alder cycloaddition of 4-methylene-1,5-hexadien-3-ols with olefinic dienophiles such as dimethyl maleate, fumarate, and N-methylmaleimide produces 1-(1-cyclohexenyl)-2-propen-1-ols. These diene alcohols are oxidized with activated manganese(IV) oxide to give dienones, which are then treated with acid catalysts to undergo ready electrocyclization leading to hexahydroindenones with functional groups. Stereoselectivity at the electrocyclization step is found to depend upon the stereostructures of cyclohexene skeleton of the dienones as well as the reaction conditions.

An Entry to 5-(1-Alkenyl)-3(2H)-furanones through Cycloaddition of Phosphorus-Functionalized Nitrile Oxide to Acetylene Alcohols. An Effective Synthesis of Geiparvarin

Abstract: Cycloaddition of α-(diethoxyphosphoryl)acetonitrile oxide to acetylene alcohols is followed by an alkylation, a reductive cleavage of the N–O bond, and an acid-catalyzed cyclization to form 5-(diethoxyphosphorylmethyl)-3(2H)-furanones in good yields. Subsequent Horner-Emmons olefination using triethylamine and lithium bromide furnishes E-isomers of 5-(1-alkenyl)-3(2H)-furanones as major products. This method has been applied to a short synthesis of Geiparvarin.

Preparation of Arylsulfonyl-Substituted 3,8-Diphenyl-1,2-diazacycloocta-2,4,6,8-tetraenes and Their Thermolysis

Abstract: Nucleophilic substitution of 4,7-dichloro-3,8-diphenyl-1,2-diazocine with benzenesulfinate gave stable 7-chloro-4-phenylsulfonyl- and 4,7-bis(phenylsulfonyl)-1,2-diazocine. The 4-mono(arylsulfonyl)- and 4,7-bis(arylsulfonyl)-1,2-diazocines were obtained by oxidation of the corresponding mono(arylthio)- and bis(arylthio)-1,2-diazocines, respectively. 4-Phenylsulfonyl-7-phenylthio-1,2-diazocine was also prepared. Thermolysis of all the diazocines gave only pyridine derivatives, and the feature of the thermolysis was also described.

Novel Ring Contraction of 1,2-Diazocine System. Hydrolysis of 7-Substituted 4-Acetoxy- and 4-Phthalimido-3,8-diphenyl-1,2-diazocines Leading to the Formation of Pyrazoles

Abstract: A novel ring contraction of 1,2-diazocine system to pyrazoles via [5.5]bicyclic intermediates has been demonstrated by hydrolysis of 7-substituted 4-acetoxy- and 4-phthalimido-3,8-diphenyl-1,2-diazocines.

An Entry to 5-(1-Alkenyl)-3(2H)-furanones Through Cycloaddition of Phosphorus-Functionalized Nitrile Oxide to Acetylene Alcohols. An Effective Synthesis of Geiparvarin.

Abstract: Cycloaddition of α-(diethoxyphosphoryl)acetonitrile oxide to acetylene alcohols is followed by an alkylation, a reductive cleavage of the N–O bond, and an acid-catalyzed cyclization to form 5-(diethoxyphosphorylmethyl)-3(2H)-furanones in good yields. Subsequent Horner-Emmons olefination using triethylamine and lithium bromide furnishes E-isomers of 5-(1-alkenyl)-3(2H)-furanones as major products. This method has been applied to a short synthesis of Geiparvarin.

Photoadducts of 4,6-Dimethyl- and 4-Methoxy-6-methyl-2-pyrones with Chloroethylenes and Their Dehydrochlorination.

Abstract: Sensitized photoreactions of 2-pyrones with chloroethylenes gave two kinds of [2+2]cycloadducts, 2-oxabicyclo[4.2.0]oct-4-en-3-ones (4, 8) and across the C3–C4 double bond in 2-pyrone, benzene derivatives, and/or cyclobutanecarboxylic acids: Their relative yields greatly depended upon the nature of the reactants. The dehydrochlorination of the cycloadducts 4 and 8 across the C5–C6 double bonds in the pyrones with triethylamine in ethanol gave 5-ethenyl-2-pyrones, whose structures were previously incorrectly assigned as oxocinones, via a symmetry-allowed ring opening of 2-oxabicyclo[4.2.0]octa-4,6-dien-3-ones. Some 5-ethenyl-2-pyrones possessing a chlorinated ethenyl group finally affords 5-ethynyl-2-pyrones by an anti-elimination of hydrogen chloride. The X-ray crystallographic analyses of 5-ethenyl- and 5-ethynyl-2-pyrones are also described.

Synthesis and Consecutive Double Diels-Alder Cycloadditions of 3-Methylene-5-phenylsulfinyl-1-pentene as a Synthetic Equivalent of Parent Cross-Conjugated Triene, 3-Methylene-1,4-pentadiene.

Abstract: 3-Methylene-5-phenylsulfinyl-1-pentene undergoes stepwise double Diels–Alder cycloadditions with two different dienophiles to afford hydronaphthalene skeletons. This sequence corresponds to cross t...

Preparation of Arylsulfonyl-Substituted 3,8-Diphenyl-1,2-diazacycloocta-2,4,6,8-tetraenes and Their Thermolysis.

Abstract: Nucleophilic substitution of 4,7-dichloro-3,8-diphenyl-1,2-diazocine with benzenesulfinate gave stable 7-chloro-4-phenylsulfonyl- and 4,7-bis(phenylsulfonyl)-1,2-diazocine. The 4-mono(arylsulfonyl)- and 4,7-bis(arylsulfonyl)-1,2-diazocines were obtained by oxidation of the corresponding mono(arylthio)- and bis(arylthio)-1,2-diazocines, respectively. 4-Phenylsulfonyl-7-phenylthio-1,2-diazocine was also prepared. Thermolysis of all the diazocines gave only pyridine derivatives, and the feature of the thermolysis was also described.

Synthesis of Arylthio-Substituted 3,8-Diphenyl-1,2-diazacycloocta-2,4,6,8-tetraenes and Their Thermolysis.

Abstract: Nucleophilic substitution of 4,7-dichloro-3,8-diphenyl-1,2-diazocine with succinimide, phthalimide, N-methyl-p-toluenesulfonamide, and o-benzosulfimide, in the presence of silver oxide, gave the corresponding 4-mono(imido)- and 4,7-di(imido)-1,2-diazocines. 4-Acetoxy-7-phthalimido- and 4-phenylthio-7-phthalimido-1,2-diazocine were also prepared. Thermolysis of the mono(imido)-1,2-diazocines in xylene under reflux afforded the corresponding di(imido)-1,2-diazocine and/or five pyridine derivatives, whose relative yields depended upon the nature of imido substitutents in the diazocines. However, 4,7-di(imido)-1,2-diazocines did not decompose in xylene under reflux. Thermolysis of 4,7-bis(phthalimido)-1,2-diazocine at 300–310 °C gave 3,6-bis(phthalimido)-2-phenylpyridine with the extrusion of benzonitrile. In the thermolysis of the acetoxy(230–240 °C) or phenylthio-substituted 1,2-diazocine (240–260 °C), 6-acetoxy- and 6-benzoyl-3-phthalimido-2-phenylpyridine, or 6(and 3)-phenylthio-3(and 6)-phthalimido-2-phe...

Stable Configuration of Ester-Stabilized Azomethine Ylides. Stabilization of anti-Form by 1,5-Dipolar Interaction and of syn-Form by Hydrogen Bonding.

Abstract: Stable configuration of ester-stabilized azomethine ylides is found to depend upon the substituent on the ylide nitrogen. Thus, N-substituted azomethine ylides derived from N-substituted 2-aminoacetates and carbonyl compounds undergo cycloaddition with olefinic dipolarophiles predominantly in anti forms, while N-protonated (or N-unsubstituted) azomethine ylides generated from 2-iminoacetates exclusively in syn forms.

Regioselective Cycloadditions of N-Protonated Azomethine Ylides and 2-Azaallyl Anions Generated from N-(Silylmethyl) Thioimidates, Synthetic Equivalents of Nonstabilized Nitrile Ylides.

Abstract: Cycloadditions dipolaires 1,3 des ylures obtenus par desilylation en presence d'eau de N-trimethylsilylmethyl thiocarboximidates(A); additions des carbanions obtenus par desilylation directe des composes A ou du S,S-dimethyl N-trimethylsilylmethyl dithiocarbonimidate avec des composes ethyleniques ou des composes carbonyles

Novel Ring Contraction of 1,2-Diazocine System. Hydrolysis of 7-Substituted 4-Acetoxy- and 4-Phthalimido-3,8-diphenyl-1,2-diazocines Leading to the Formation of Pyrazoles.

Abstract: A novel ring contraction of 1,2-diazocine system to pyrazoles via [5.5]bicyclic intermediates has been demonstrated by hydrolysis of 7-substituted 4-acetoxy- and 4-phthalimido-3,8-diphenyl-1,2-diazocines.

Synthesis of Vinylcyclopropanes, Cyclopropyl Vinyl Ketones, and 3-Pyrazolyl Vinyl Ketones from 1-Diazo-3-trimethylsilylpropanone.

Abstract: Reaction of 1-diazo-3-trimethylsilylpropanone with olefins in the presence of cupric acetylacetonate (Cu(acac)2) affords cyclopropyl trimethylsilylmethyl ketones. One-flask procedure for the formation of these silylated ketones and subsequent treatment with organometallics or with lithium diisopropylamide (LDA) and then carbonyl compounds gives a variety of vinylcyclopropanes or cyclopropyl vinyl ketones in good yields, respectively. Cycloaddition of 1-diazo-3-trimethylsilylpropanone with acetylenes and similar carbon–carbon bond formation at the side chain of the cycloadducts lead to 3-pyrazolyl vinyl ketones.

Reactions of 1,4-Bis(trimethylsilyl)-1,4-dihydropyridines with Carbonyl Compounds: A New Method for Regioselective Synthesis of 3-Alkylpyridines.

Abstract: A new method for the alkyl group introduction at the 3-position of pyridienes is described: Reductive disilylation of pyridine, its 2-methyl, 3-methyl, and 4-methyl derivatives affords the corresponding 1,4-disilyl-1,4-dihydropyridines. In the presence of a catalytic amount of tetrabutylammonium fluoride, these dihydropyridines smoothly react with a variety of aldehydes and ketones to give 3-alkylpyridines.

Synthetic Versatility of N-(Silylmethyl)imines: Water-Induced Generation of N-Protonated Azomethine Ylides of Nonstabilized Type and Fluoride-Induced Generation of 2-Azaallyl Anions.

Abstract: N-(Silylmethyl)imines generate N-protonated azomethine ylides of nonstabilized type when treated with water in HMPA, which undergo stereospecific and regioselective cycloadditions with electron-poo...

Synthesis of Hexahydroindenones Through a Diels-Alder Cycloaddition and Nazarov Cyclization Sequence of Triene Alcohols.

Abstract: The Diels–Alder cycloaddition of 4-methylene-1,5-hexadien-3-ols with olefinic dienophiles such as dimethyl maleate, fumarate, and N-methylmaleimide produces 1-(1-cyclohexenyl)-2-propen-1-ols. These diene alcohols are oxidized with activated manganese(IV) oxide to give dienones, which are then treated with acid catalysts to undergo ready electrocyclization leading to hexahydroindenones with functional groups. Stereoselectivity at the electrocyclization step is found to depend upon the stereostructures of cyclohexene skeleton of the dienones as well as the reaction conditions.

Stereoselective Cycloadditions of Pyridinium or Isoquinolinium Methylides with Olefinic Dipolarophiles and Subsequent Cycloadditions of the Cycloadducts with Nitrile Oxides.

Abstract: Pyridinium or isoquinolinium methylides undergo highly stereo- and regioselective cycloadditions with olefinic dipolarophiles to form unstable tetrahydroindolizine derivatives. One of the two double bonds existing in the dihydro heteroaromatic ring of the cycloadducts reacts with nitrile oxides, in the same flask, in stereo-, regio-, and periselective fashions to lead to stable isoxazole-fused tetrahydroindolizines in good yields.