Recyclization of 2-alkoxycarbonylmethyl-1,5-diaryl-2-hydroxy-2,3-dihydropyrrol-3-ones by hydrazine

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, p. 1698, December, 1988.     

Stereoselective synthesis of chiral 3,4,5-trisubstituted 1,5-dihydropyrrol-2-ones from azadienes

A new access to enantiopure 3-phthalimido-4-amino-5-(1-hydroxyalkyl) 1,5-dihydropyrrol-2-ones has been developed from 1,3-azadienes. Stereoselective Lewis acid catalyzed addition of a cyano group to an azadiene, followed by intramolecular ring closure, in a four-step one-pot synthesis, results in the formation of γ-lactams in satisfactory yields.     

Five-membered 2,3-dioxo heterocycles. 2. Synthesis and [1,5]-sigmatropic rearrangement of 4-acyl-3-diphenylmethoxy-1,5-diphenyl-2,5-dihydropyrrol-2-ones

4-Acyl-1,5-diphenyltetrahydropyrrole-2,3-diones react with diphenyldiazomethane to give O-alkylation products, which upon heating undergo [1,5]-sigmatropic suprasurface rearrangement to form 4-[methyl- and 4-[-aryl(diphenylmethoxy)-methylene]-1,5-diphenyltetrahydropyrrole-2,3-diones.See [1] for Communication 1.Translated from Khimiya Geterotsiklicheskikh Soedinenii. No. 5, pp. 625–628, May, 1987.     

Synthesis of 1,5-diazocin-2-ones

Russian Chemical Bulletin - This review is focused on the synthetic approaches to the eight-membered nitrogen heterocycles, 1,5-diazocin-2-ones, exhibiting promising biological activities....     

Five-membered 2,3-dioxoheterocycles 15. Synthesis and [1,3]-sigmatropic rearrangement of 1,5-diaryl-3-diphenylmethoxy-4-ethoxycarbonyl-2,5-dihydropyrrol-2-ones

Ethyl oxaloacetate reacts with a mixture of an aromatic aldehyde and an arylamine to give 1,5-diaryl-4-ethoxycarbonyltetrahydropyrrole-2,3-diones, which react with diphenyldiazomethane to give the O-alkylation products. On heating, the latter undergo suprafacial [1,3]-sigmatropic rearrangement to 1,5-diaryl-4-diphenylmethyl-4-ethoxycarbonyltetrahydropyrrole-2,3-diones. The effects of the type of migrating group on the rearrangement are discussed.For Communication 14, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 753–757, June, 1990.     

Preparation of 1,5-disubstituted pyrrolidin-2-ones

1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.     

Preparation and intramolecular [2+2]-photocycloaddition of 1,5-dihydropyrrol-2-ones and 5,6-dihydro-1H-pyridin-2-ones with C-, N-, and O-linked alkenyl side chains at the 4-position

The 1,5-dihydropyrrol-2-ones 2, 6, 9, and 11 were prepared from methyl tetramates (1a-c), N-Boc-protected tetramic acid (3), or N-Boc-protected tetramic acid bromide (7) in short reaction sequences and in very good overall yields. The homologous 5,6-dihydro-1H-pyridin-2-ones 16, 18, 20, 21, 23, and 27 were prepared along analogous routes starting from piperidin-2,4-dione (19) or from its N-tert-butyl derivative 15. Optimized conditions for the [2+2]-photocycloaddition include the use of dichloromethane as the solvent and an irradiation with a mercury low-pressure lamp (lambda = 254 nm). Upon applying these conditions at ambient temperature, the corresponding intramolecular photocycloaddition products 28-37 were obtained in good yields (52-79%) and with perfect diastereoselectivity. The constitution and configuration of the products was elucidated by NMR-spectroscopy. For the O-tethered substrates 2a and 20, a strong decrease of the photocycloaddition rate with temperature was observed. The effect was less pronounced for N- and C-tethered substrates 6, 9, 23, and 27. The use of a chiral complexing agent to achieve enantioselective reactions appears viable. Complexing agent (-)-38, however, is not suited because of its instability at lambda = 254 nm.     

Nucleophilic Substitution in 1,5-Benzodiazepin-2-ones

The reaction of 3-bromo-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one with cyclic amines gives 3-aminoalkyl-4-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-2-one. Thiazolo[4,5-b][1,5]benzodiazepine was isolated along with the substitution product when thiourea was used.     

Diastereoselective synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones via a nitro-Mannich/lactamization cascade

A versatile one-pot nitro-Mannich/lactamization cascade for the direct synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones has been developed. The reaction is easy to perform and broad in scope, and high levels of diastereoselectivity can be achieved.     

Regioselective synthesis of o-triazolyl-1,5-benzodiazepin-2-ones and o-isoxazolyl-1,5-benzodiazepin-2-ones via copper-catalyzed 1,3-dipolar cycloaddition reactions

A series of novel O-triazolyl-1,5-benzodiazepin-2-ones 6a–o and O-isoxazolyl-1,5-benzodiazepin-2-ones 7a–o was synthesized via a Cu(I)-catalyzed 1,3-dipolar alkyne–azide coupling reaction of N-substituted-1,5-benzodiazepine–alkyne derivatives 3a–c with various aromatic azides 4a–e and nitrile oxides 5a–e, respectively. The chemical structures of synthesized compounds were determined using ¹H NMR, ¹³C NMR, heteronuclear multiple bond correlation (HMBC), high-resolution mass spectra, as well as elemental analysis and was further confirmed by an X-ray diffraction analysis for compound 7d.     

An efficient stereoselective synthesis of 4,5-trans-1,5-cis-3-oxabicyclo[3.1.0]hexan-2-ones via the iodolactonization of alkylidenecyclopropyl esters

[reaction: see text] A highly stereoselective iodolactonization of alkylidenecyclopropyl esters with iodine or N-iodosuccinimide (NIS) in aqueous CH3CN to afford 4,5-trans-1,5-cis-3-oxabicyclo-[3.1.0]hexane-2-ones is described. The reaction is very general, accommodating a wide range of substituents. A plausible mechanism that explains the essential role of water in this reaction is proposed.     

An efficient approach to 3,4-disubstituted pyridin-2-ones. Formal synthesis of mappicine ketone

Treatment of 3,4-dihydro-3-tosylpyridin-2-one 5 with sodium hydride and then alkyl halides gave various 3,4-disubstituted pyridin-2-ones 6. Formal synthesis of mappicine ketone (1) was also reported.     

Solution-phase parallel synthesis of diverse 1,5-benzodiazepin-2-ones

A practical and efficient parallel method has been developed for the synthesis of 1,5-benzodiazepin-2-ones with a large variety of substituents at the 3-, 4-, 5-, 7-, and 8-positions using 1,5-difluoro-2,4-dinitrobenzene as the starting material. All the reactions involved here are highly effective in giving the desired products under mild conditions.     

Convenient Synthesis of 7-Bromo-tetrahydro-1,5-benzodiazepin-2-ones

Treatment of 5-acyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-2-ones with bromine in the presence of the sulfuric acid afforded products to be brominated exclusively in the aromatic ring at position 7.     

A novel route to substituted 3-methylidenechroman-2-ones and 3-methylchromen-2-ones

3-Methylidenechroman-2-ones, or their rearrangement products 3-methylchromen-2-ones, were efficiently synthesized by Michael addition of various nucleophiles to 3-diethoxyphosphorylchromen-2-ones followed by Horner-Wadsworth-Emmons reaction of the adducts with formaldehyde. Relative configuration and conformation of the intermediate adducts were studied using NMR spectroscopy and semiempirical PM3 calculations.     

Heterocyclization of Derivatives of 4-Oxoalkanoic Acids to 1,5-Disubstituted Pyrrolin-2-ones

Conditions were developed for the synthesis and production of 1-aryl-5-alkyl(aryl)-3H- and 1-aryl-5-alkyl(aryl)-5H-pyrrolin-2-ones from the amides and esters of 4-oxoalkanoic acids. It was established that the yield and ratio of the 3H and 5H isomers depend on the substrate employed in the reaction.     

Uncatalyzed synthesis of 3-amino-1,5-dihydro-2H-pyrrol-2-ones

Uncatalyzed one-pot pseudo-four-component reaction of ethyl pyruvate, anilines, and aldehydes in n-hexane as solvent, under reflux, affords a variety of 3-amino-1,5-dihydro-2H-pyrrol-2-ones in high yield. n-Hexane is an excellent driving force in preparation of the desired products. These compounds have biological and pharmacological properties and are also used in medicinal chemistry. Use of a non-toxic and inexpensive solvent, simple and efficient synthesis, clean work-up, and high yields of the products are the advantages of this method. We report the first catalyst-free method for synthesis this class of compounds.     

Stereoselective synthesis of densely functionalized pyrrolidin-2-ones by a conjugate addition/nitro-Mannich/lactamization reaction

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate 1 followed by a subsequent nitro-Mannich reaction and in situ lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (5). The versatility of the reaction is shown for a wide range of N-p-(methoxy)phenyl protected aldimines 3 derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones 5 are isolated as single diastereoisomers (40 examples, 33-84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis.     

Bromination of aromatic ring of tetrahydro-1,5-benzodiazepin-2-ones

Novel mono- or dibromo-substituted tetrahydro-1,5-benzodiazepinones were obtained by direct bromination of the corresponding 2,3,4,5-tetrahydro-(1H)-1,5-benzodiazepin-2-ones and 5-N-alkyl (or formyl) derivatives with bromine. Substituent effects and the orientation of the entering groups in the bromination reaction are discussed.Institute of Biochemistry, Vilnius LT-2600, Lithuania; c-mail: apalaima@bchi.lt. Translated from Khimiya Geterotsiklicheskikh Socdinenii, No. 6, pp. 799–805, June, 2000.