Substituent-controlled domino-Knoevenagel-hetero Diels-Alder reaction—a one-pot synthesis of polycyclic heterocycles

The reaction of 2-(N-alkenyl-N-aryl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde with dimedone/Meldrum’s acid/4-hydroxycoumarin by heating in ethanol in the presence of pyridine produces polycyclic heterocycles bearing pyridine and pyran rings in a one-pot reaction. The effect of substituents on N-atom of the amino function controls the mode of reaction. Terminal alkenes prefer intramolecular Michael type reaction, but non-terminal alkenes favour Diels-Alder reaction, whereas, under similar condition, 2-(N-alkyl-N-allyl)amino-4-oxo-4H-1-benzopyran-3-carbaldehyde undergoes domino-Knoevenagel-hetero Diels-Alder reaction.     

Reaction of 3-chloroquinoline-2,4-diones with ethanolamine and rearrangement of the reaction products

The reaction of tertiary α-chloroketones with ethanolamine has not been hitherto described in the literature. Herein, we describe the reaction of tertiary 3-chloroquinoline-2,4-diones with ethanolamine to give novel 3-(2-hydroxyethylamino)quinoline-2,4-diones. These compounds provide 3-(2-oxooxazolidin-3-yl)quinoline-2,4(1H,3H)-diones and new compounds with dimeric character after reaction with triphosgene. Molecular rearrangement proceeds during the reaction of 3-(2-hydroxyethylamino)quinoline-2,4-diones with isocyanic acid. Three types of reaction products arise: 2-(2-hydroxyethyl)imidazo[1,5-c]quinazoline-3,5-diones, 3-(2-hydroxyethyl)-3,3a-dihydro-2H-imidazo[4,5-]quinoline-4(5H)diones and primarily 5-hydroxy-1-(hydroxyethyl)-1′H-spiro[imidazolidine-5,3′-indole]-2,2′-diones. The reaction mechanism and product stereochemistry are discussed. The ¹H, ¹³C and ¹⁵N NMR spectra of the prepared compounds were measured, and all resonances were assigned from appropriate two-dimensional experiments.     

Chiral diphenylselenophosphoramides: a new class of chiral ligands for the titanium(IV) alkoxide-promoted addition of diethylzinc to aldehydes

Chiral C₂-symmetric diphenylselenophosphoramides 1 and 2 were prepared from the reaction of diphenylselenophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively, in high yields. Another novel chiral ligand 3 was prepared from the reaction of diphenylselenophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as the base. The ligands were used as catalytic chiral ligands in the titanium(IV) alkoxide-promoted enantioselective addition reaction of diethylzinc to aldehydes.     

Chiral diphenylthiophosphoramides: a new class of chiral ligands for the silver(I)-promoted enantioselective allylation of aldehydes

Chiral C₂-symmetric diphenylthiophosphoramides 1 and 2 were prepared in high yields from the reaction of diphenylthiophosphinic chloride with (1R,2R)-(−)-1,2-diaminocyclohexane and (1R,2R)-(+)-1,2-diphenylethylenediamine, respectively. Another novel chiral ligand 4 was prepared from reaction of diphenylthiophosphinic chloride with (R)-(+)-1,1′-binaphthyl-2,2′-diamine using butyllithium as a base. They were used as catalytic chiral ligands in the silver(I)-promoted enantioselective allylation reaction of aldehydes with allyltributyltin.     

Stereoselective total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (−)-(6S,2′S)-epi cryptocaryalactone via asymmetric acetate aldol reaction

The total synthesis of (+)-(6R,2′S)-cryptocaryalactone and (?)-(6S,2′S)-epi cryptocaryalactone is reported based on asymmetric acetate aldol reaction. Still–Gennari reaction, Evans acetal intramolecular oxa-Michael reaction and lactonisation are the key steps in the target synthesis.     

Facile stereoselective synthesis of (E)- and (Z)-α-substituted cinnamates: stereospecific dehydration reaction with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and copper(II) chloride

A highly stereoselective method for the synthesis of (E)- and (Z)-α-substituted cinnamates in good yield has been achieved by dehydration reaction of anti- and syn-α-substituted-β-hydroxyphenylpropiolate using EDC. This facile method has been used to synthesize various (E)- and (Z)-α-substituted cinnamates and (E)- and (Z)-α-alkylidene-γ-butyrolactones. The reaction mechanism of this highly stereospecific dehydration using EDC can be elucidated by the ω-dimethylamino group of EDC, which is believed to facilitate the deprotonation step.     

Novel (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles from (E)- and (Z)-3-styrylchromones: the unexpected case of (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles

An efficient synthetic method for the preparation of (E)- and (Z)-3(5)-(2-hydroxyphenyl)-4-styrylpyrazoles has been developed. The reaction of (E)- and (Z)-3-styrylchromones with hydrazine hydrate afforded the corresponding (E)- and (Z)-4-styrylpyrazoles, respectively, saved 4′-nitro-derivatives where both (E)- and (Z)-4′-nitro-3-styrylchromones afforded (E)-3(5)-(2-hydroxyphenyl)-4-(4-nitrostyryl)pyrazoles. The reaction mechanism for these transformations was discussed and the stereochemistry of all products was assigned by NMR experiments.     

A practical synthesis of new S,N-disubstituted derivatives of 5-(4-methylpiperidino)methyl-2-thiouracil

5-(4-Methylpiperidino)methyl-2-thiouracil (1) has been obtained via the Mannich reaction between 2-thiouracil, paraformaldehyde, and a cyclic secondary amine such as 4-methylpiperidine (4-MP) in ethanol. New S,N(1)-di-o-(m- and p-)bromo-(nitro-) benzyl-substituted derivatives have been synthesized successfully in the reactions of 1 with the corresponding o-(m- and p-)bromobenzyl bromides or o-(m- and p-) nitrobenzyl chlorides in DMF solution in the presence of K₂CO₃. The opposite method of synthesis, that is, the reaction between 2-o-(m- and p-)bromobenzylthio-1-o-(m- and p-)bromobenzyluracils and 2-o-(m- and p-)nitrobenzylthio-1-o-(m- and p-) nitrobenzyluracils (8), with paraformaldehyde and 4-methylpiperidine in ethanol failed, indicating the important role of the enol form of 2-thiouracil for the Mannich reaction to be successful.     

Zinc chloride catalyzed three-component Ugi reaction: synthesis of N-cyclohexyl-2-(2-hydroxyphenylamino)acetamide derivatives

The ability of zinc chloride as a catalyst to promote the three-component Ugi reaction of 2-aminophenols, aliphatic or aromatic aldehydes, and cyclohexyl isocyanide in methanol at room temperature is described. The N-cyclohexyl-2-(2-hydroxyphenylamino) amide products are obtained in high yields. When N,N-dimethylformamide dimethyl acetal and triethyl orthoformate, as two new components of the three-component Ugi reaction are used instead of the aldehyde the reaction gives N-cyclohexyl-2-(dimethylamino)-2-(2-hydroxyphenylamino)acetamide and N-cyclohexyl-2-(2-hydroxyphenylamino)-2-ethoxyacetamide derivatives, respectively.     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

Synthetic and structural study of 4-phosphacyclohexanones and 3-aza-7-phosphabicyclo[3.3.1]nonan-9-ones

The synthesis of bicyclic phosphorus–nitrogen (PN) compounds containing the rigid bicyclo[3.3.1]nonan-9-one framework was attempted using the Mannich condensation reaction of four different phosphorinanone classes with amines and aldehydes. Three different isomers of 4-tert-butyl-2,6-di(methoxycarbonyl)-3,5-bis(p-dimethylaminophenyl)-4-phosphacyclohexanone were obtained from the Michael addition reaction of tert-butylphosphine with 2,4-di(methoxycarbonyl)-1,5-bis(p-dimethylaminophenyl)penta-1,4-dien-3-one. The reaction of the all-equatorial isomer with methylamine and formaldehyde produced the bicyclic PN compound 7-tert-butyl-1,5-di(methoxycarbonyl)-6,8-bis(p-dimethylaminophenyl)-3-methyl-3-aza-7-phosphabicyclo[3.3.1]nonan-9-one. The identical Mannich reaction of the enol tautomer also yielded the same product, as well as the PN compound 4-tert-butyl-6-methoxycarbonyl-5-(p-dimethylaminophenyl)-2-methyl-2-aza-4-phosphacyclohexanone and the E/Z isomers of 3-(p-dimethylaminophenyl)methyl-2-propenoate. The newly synthesised 3-aza-7-phosphabicyclo[3.3.1]nonan-9-one PN compound adopts a chair–chair conformation both in solution and the solid state.     

Prins and RCM protocols for the synthesis of the pheromones of the giant white butterfly Idea leuconoe

The total syntheses of (6R)-6-[(2R)-2-hydroxyhexyl]tetrahydro-2H-2-pyranone and 7-hydroxy-5-dodecanolide are described utilizing a Prins reaction and ring closing metathesis reaction sequence.     

Selective mono-acylation of 1,2- and 1,3-diols using (α,α-difluoroalkyl)amines

In the reaction of N,N-diethyl-α,α-difluorobenzylamine (DFBA) with 1,2- or 1,3-diols, selective mono-benzoylation occurs to afford mono-esters of the diols in good yield. The reaction is completed under mild conditions in a short reaction time. Further, prim-, sec-, and tert-diols and catechol can be converted to the corresponding mono-benzoates. DFBA is used for the protection of the hydroxy group in sugars. The selective mono-nicotinylation, formylation and pivaloylation of diols are also performed by using the corresponding difluoroalkylamines.     

Reaction between tert-butyl isocyanide, dialkyl acetylenedicarboxylates, and aromatic carboxylic acids: an efficient method for the synthesis of dialkyl (E)-2-{[benzoyl(tert-butyl)amino]carbonyl}-2-butenedioate derivatives

Protonation of the reactive intermediates produced in the reaction between tert-butyl isocyanide and dialkyl acetylenedicarboxylates by aromatic carboxylic acids leads to vinylnitrilium cations, which undergo nucleophilic reaction with conjugate bases of the carboxylic acids to produce dialkyl (E)-2-[(benzoyloxy)(tert-butylimino)methyl]-2-butenedioates and this intermediate rearranges to the dialkyl (E)-2-{[benzoyl(tert-butyl)amino]carbonyl}-2-butenedioate derivatives.     

A novel and practical synthesis of S-(1- and 2-halogenoalkyl)sugars by reaction of carbohydrate S-(O,O-dialkyl)phosphorodithioates and monothioates with fluoride anion

A useful synthesis has been developed of S-(1- and 2-halogenoalkyl)sugars in high yield and purity. Readily available sugar S-(O,O-dialkyl)phosphorodithioates undergo S-P bond rupture on reaction with fluoride ions to yield the corresponding sugar thiolates, which further react in situ with dichloromethane or 1,2-dihalogenoalkanes in the reaction medium. In this reaction, the halogenoalkanes play the role of both reactants and solvents.     

Synthesis of eleven-membered carbocycles via a homo-Cope type of five-carbon ring expansion reaction utilized β-(hydroxymethyl)allylsilane

Eleven-membered carbocycles were synthesized from six-membered compounds fitted with a β-(hydroxymethyl)allylsilane unit via the title reaction. Namely, trans- and cis-(E)-2-(trimethylsilylmethyl)-3-(2-vinylcyclohex-1-yl)prop-2-en-1-ol were treated with Tf₂O in CH₂Cl₂ in the presence of 2,6-lutidine to afford (1E)-3-methylenecycloundeca-1,6-diene in good yield. The geometry of the product was shown to depend upon the trans- and cis-substitution pattern on the cyclohexane ring of the substrates; i.e. trans-isomer afforded (6E)-product exclusively and cis-isomer afforded the mixture of (6E)- and (6Z)-product in 1:2 ratio. The (Z)-substrate with respect to allylsilane moiety afforded the same ring expansion product, however, the yield was lower than the reaction with the (E)-substrate. The substrates bearing t-butyl or benzyloxy substituents on the cyclohexane ring also afforded the product analogously, indicating that the reaction depends upon the conformation of the substrate. On the other hand, the substrate bearing isopropenyl group instead of a simple vinyl group did not afford the ring expansion product but produced bicyclo[5.4.0]undecane via the ene reaction.     

Thermal cyclization of N-[2-(2-propenyl)-1-naphthyl] ketenimines: intramolecular Diels-Alder reaction versus [1,5] hydrogen migration. Synthesis of dibenz[b,h]acridines and benzo[h]quinolines

The thermal treatment of N-(2-propenyl)-1-naphthylamines provided the expected aza-Claisen rearranged products, 2-(2-propenyl)-1-naphthylamines and benz[g]indoles, these last derived from an intramolecular hydroamination reaction on those primary products. The 2-(2-propenyl)-1-naphthylamines were converted into their triphenylphosphazene derivatives, which by aza-Wittig reaction with disubstituted ketenes yielded N-[2-(2-propenyl)-1-naphthyl] ketenimines. The heating of these ketenimines in boiling toluene induced their cyclization either via an intramolecular Diels-Alder reaction, to afford dibenz[b,h]acridines, or via [1,5] hydrogen migration from the sp³ carbon atom of the propenyl substituent to the central carbon atom of the ketenimine fragment, followed by a 6π electrocyclic ring closure, to give benzo[h]quinolines.     

Exact results on the relaxation spectrum of a simple model for micelle formation

We consider the reaction scheme A₁ + A_i ? A_i+1 (i - 1,2, …, n), where the equilibrium of the first n - 1 reactions is strongly shifted towards the left while the equilibrium of the nth reaction is strongly shifted towards the right as a model for formation of micelles and prove that under reasonable assumptions the relaxation spectrum has one relaxation time corresponding to the gross reaction (n = 1)A_n ? A_n+1 and, at much higher frequencies, a cluster of relaxation times corresponding to the n - 1 first reactions.     

Synthesis of glyco-1-ynitols via 1,1-dibromo-1-alkenes from partially and unprotected aldoses

We report the synthesis of 1,1-dibromo-1-alkenes from partially and unprotected aldoses and the synthesis of glyco-1-ynitols from these dibromocompounds. The 1,1-dibromo-1-alkenes were obtained by the reaction of dibromomethyl-triphenylphosphonium bromide in the presence of zinc in refluxing 1,4-dioxane. As an example, when the reaction is performed on 2-deoxy-5-O-trityl-d-ribofuranose (1) the corresponding 1,1-dibromo-1-olefin, (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12), is obtained in 89% yield. These smooth reaction conditions led also to the achievement of the other olefins from other sugars with good yields (44-90%). The reaction of these olefins with n-butyllithium in THF at low temperature afforded the corresponding alkynes. So the reaction of (2R,3S)-6,6-dibromo-1-O-trityl-hex-5-ene-1,2,3-triol (12) with this alkyllithium reagent led to (2R,3S)-1-O-trityl-hex-5-yne-1,2,3-triol (23) in 87% yield. Other glyco-1-ynitols were obtained with satisfying yields (64-87%).     

The reaction of (Sp)-2-(diphenylphosphino)ferrocenecarboxylic acid with carbodiimide reagents: Characterisation of the acid anhydride and urea products

Interaction of (S_p)-2-(diphenylphosphino)ferrocenecarboxylic acid [(S_p)-1] with N,N′-dicyclohexylcarbodiimide (DCC) and N-ethyl-N′-[3-(dimethylamino)propyl]carbodiimide (EDC) have been investigated in order to study the reacting system itself and to characterise side-products typically arising during the diimide-promoted condensation of acid (S_p)-1 with nucleophiles. The reaction between (S_p)-1 and DCC was found to give preferentially the respective urea derivative in the absence of a base, and (S_p)-2-(diphenylphosphino)ferrocenecarboxylic anhydride [(S_p,S_p)-3] when the same reaction was performed in the presence of 4-(dimethylamino)pyridine (DMAP). With EDC, the preference for a reaction pathway was less pronounced: whereas the reaction without the base afforded exclusively the corresponding urea, that in the presence of DMAP yielded a mixture of the urea and anhydride (S_p,S_p)-3.