Synthesis of ethyl 4-chloro-2-oxobut-3-ynoate and its addition to alkyl vinyl ethers

Ethyl 4-chloro-2-oxobut-3-ynoate has been synthesized for the first time and its addition to alkyl vinyl ethers of various structures has been studied. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1537–1539, July, 2008.     

Catalytic enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one by chiral copper catalyst

A new catalytic system for enantioselective [2+2]-cycloaddition reaction of 2-methoxycarbonyl-2-cyclopenten-1-one with thioacetylene derivatives is described. The use of a catalytic amount (20-30 mol%) of copper(II) salt with chiral bis-pyridine ligand was found to be effective in promoting the [2+2]-cycloaddition reaction, furnishing the corresponding bicyclic compound in good yield and good enantioselectivity.     

Stereospecific [2+2] cycloaddition reactions of diphosphorus with alkenes

[2+2] Cycloaddition reactions of P₂ with alkenes were predicted to have concerted paths, that is, pseudoexcitation, distorted 2π_s+2π_s, and 2π_s+2π_a processes without any interventions of intermediates. The pseudoexcitation and/or distorted 2π_s+2π_s paths with retention of configuration of alkenes are kinetically preferred to the 2π_s+2π_a path with inversion of configuration. The reactions were predicted from the appreciable difference in the calculated enthalpies of activation to be stereospecific.     

Synthesis of substituted imidazolines via [3+2]-cycloaddition of aziridines with nitriles

An efficient synthesis of 2,4-disubstituted 1H-imidazolines from aziridines and nitriles in the presence of BF₃-Et₂O or triethyloxonium tetrafluoroborate has been described. The reaction proceeds via a [3+2]-cycloaddition reaction. Most of the nitriles successfully underwent cycloaddition reactions with aziridines even at room temperature in a very short time.     

Rhodium-Catalyzed Enantioselective [4+2] Cycloadditions of Vinylcarbenes with Dienes

The reaction of 2-siloxycyclo-1,3-dienes with E-vinyldiazoacetates in the presence of the bulky chiral dirhodium tetracarboxylate catalyst, Rh₂(R-p-PhTPCP)₄ results in an enantioselective [4+2] cycloaddition, in which three new stereogenic centers are formed. The [4+2] cycloadducts are generated as single diastereomers with high enantiocontrol (95–98 % ee). When the diene contains an additional stereogenic center, effective kinetic resolution can be achieved.     

Cyclobutane ring formation by triflic imide catalyzed [2+2]-cycloaddition of allylsilanes

Cyclobutane forming [2+2]-cycloaddition reactions of allylsilane with electron-deficient olefin is promoted by triflic imide (Tf₂NH). Triflic imide is converted in situ to silyl triflic imide (R₃SiNTf₂), which serves as the actual catalyst for this process. When these reactions take place at higher than ambient temperatures, thermodynamically more stable anti-cyclobutanes are generated preferentially by equilibration of the initially formed adducts via retro [2+2]-cycloaddition.     

Synthesis of 2-azaspiro[4.4]nonan-1-ones via phosphine-catalysed [3+2]-cycloadditions

The phosphine-catalyzed [3+2]-cycloaddition of the 2-methylene γ-lactams 4 and 5 and the acrylate 6 with the ylides derived from the ethyl ester, the amide or the chiral camphor sultam derivative of 2-butynoic acid (7a-c) give directly, or indirectly after reductive cyclization, spiro-heterocyclic products. The acid 32 underwent Curtius rearrangement and then acid hydrolysis to give two novel spiro-cyclic ketones, 41 and 42.     

Studies in stereoselective [2+2]-cycloadditions with dichloroketene

During the investigation of the reaction of dichloroketene with cyclic enoxy-lactones and acyclic enoxy-ester substrates it was found that only the acylic variants effectively participated in the [2+2]-cycloaddition. Although a complete understanding of the reasons for this are lacking, molecular mechanics calculations do suggest that an out of plane twist of the cabonyl group in the acyclic compounds may be partially responsible. After screening a variety of chiral auxiliaries it was found that useful levels of diastereoselectivity (2.6-10.8:1) could be obtained in this cycloaddition reaction when (R)-2,2-diphenylcyclopentanol was used as the chiral auxiliary.     

One-pot diastereoselective synthesis of tetrahydroepimino-benzo[b]azocines through sequential [3+2]-cycloaddition and Staudinger-aza-Wittig reactions

The one-pot synthesis of tetrahydro-epiminobenzo[b]azocines through a sequential 1,3-dipolar cycloaddition and intramolecular Staudinger-aza-Wittig reaction sequence is reported. This methodology provides a new and efficient approach for medium-sized and bridged nitrogen heterocyclic molecules.     

Intramolecular [2+2]-cycloaddition of propargylic 2,3-allenoates for the efficient synthesis of 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones: a dramatic substituent effect

[2+2]-Cycloaddition reactions of propargylic 2,3-allenoates under conventional heating conditions afforded 3-oxabicyclo[4.2.0]octa-1(8),5-dien-4-ones, which contain both the biologically important 5,6-dihydropyran-2-one and cyclobutene units.     

Alkoxycarbonylimines of hexafluoroacetone in reaction of [2+4]-cycloaddition

The [2+4]-cycloadditions of alkoxycarbonylimines of hexafluoroacetone to cyclopentadiene andN-nitriles have been studied. Alkoxycarbonylimines of hexafluoroacetone may be considered as both dienophiles and 1,3-heterodienes.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1809–1813, September, 1995.     

Theoretical elucidation of the rhodium-catalyzed [4 + 2] annulation reactions

The reaction mechanism of the Rh-catalyzed [4 + 2] annulation of 4-alkynals with isocyanates is unraveled using density functional calculations. The reaction mechanisms of the model system and the real substituted system have been investigated and the results are compared. From our theoretical results based on the model and real substituted system, it is shown that (a) the rate-determining step is the Rh-H addition to the alkyne, (b) the formation of the cyclopentenone G and glutarimide K represents a severe competition, and (c) the product selectivity should be controlled by the amount of the isocyanates. In addition, it is demonstrated that there exist steric effects in the real substituted system, but missed in model system. Our calculations also show that although the results obtained on the model system could explain the mechanism in principle, the real substituted system could reflect the mechanism more exactly and make the reaction proceed with regioselectivity.     

Synthesis of 1,1,1,3,3,3-hexafluoroprop-2-yl 4-bromo-2-oxobut-3-ynoate and its [2+2] cycloaddition to alkenes

Russian Chemical Bulletin -     

[4+2] Cycloaddition reactions of 4-sulfur-substituted 2-pyridones with electron-deficient dienophiles

[4+2] Cycloaddition reactions of 4-(phenylthio)-1-tosyl-2-pyridone (6a) and 4-(phenylsulfonyl)-1-tosyl-2-pyridone (6b) with electron-deficient dienophiles 7 (N-methylmaleimide, N-phenylmaleimide, and methyl acrylate) gave new isoquinuclidine products 8-10. The N-tosyl group of 6a and 6b was also efficiently converted to N-alkyl derivatives 6c-f, which showed different stereoselectivity toward reactions with dienophiles 7. Several other dienophiles 15 (dimethyl acetylenedicarboxylate, methyl vinyl ketone, ethyl vinyl ether, and methyl methacrylate) were found not to react with 6a or 6b, but led to the formation of tosyl migration products 4-(phenylthio)-O-tosyl-pyridinol (16a) and 4-(phenylsulfonyl)-O-tosyl-2-pyridinol (16b), respectively. The reactivity, regioselectivity, and stereoselectivity of the cycloaddition reactions were also compared with semi-empirical calculations.     

Expeditious synthesis of imidazo[1,2-c]pyrimidines via a [4+1]-cycloaddition

A new and versatile synthesis of imidazo[1,2-c]pyrimidines via a [4+1]-cycloaddition is described. The reported novel synthetic approach leads to pharmacologically interesting scaffolds containing three points of potential diversity, which previously were not accessible under conventional conditions. In addition, this novel synthetic procedure is amenable to the assembly of libraries with this interesting core structure.     

Versatile approach to heteroarylfuroxan derivatives from oximinofuroxans via a one-pot,nitration/thermolysis/[3+2]-cycloaddition cascade

A simple, general, and regioselective method has been developed for the synthesis of a series of heteroarylfuroxans, including isoxazolyl-, isoxazolinyl- and (1,2,4-oxadiazolyl)furoxans. The described method is based on a cascade of one-pot processes, including the nitration of furoxancarbaldehyde oximes, thermolysis of the formed nitrolic acids to generate furoxancarbonitrile oxides, and [3+2]-cycloaddition with an appropriate dipolarophile – alkynes, olefins, or activated nitriles.     

Reactivity of allenoates toward aziridines: [3+2] and formal [3+2] cycloadditions

The reactivity of buta-2,3-dienoates toward aziridines is reported. Allenoates react as 2π-component in the [3+2] cycloaddition with the azomethine ylide generated from cis-1-benzyl-2-benzoyl-3-phenylaziridine affording 4-methylenepyrrolidines in a site-, regio-, and stereoselective fashion. Under conventional thermolysis, cis- and trans-2-benzoyl-1-cyclohexyl-3-phenylaziridines showed a different reactivity. These aziridines participate in formal [3+2] cycloadditions with allenes via C-N bond cleavage of the three-membered ring leading to functionalized pyrroles.     

Reaction of ene-bis(phosphinylallenes): [2+2] versus [4+2] cycloaddition

Reaction of ene-bis(phosphinylallenes), derived from ene-bis(propargyl alcohols) and chlorodiphenylphosphine, was investigated. Benzene-bridged bis(phosphinylallenes) exclusively gave intramolecular [2+2] cycloadducts in the presence of dimethyl fumarate in sharp contrast to the reaction of benzene-bridged bis(sulfinylallenes), which gave the corresponding [4+2] cycloadducts. On the other hand, substituted ethylene- or five-membered heterocycle-bridged bis(phosphinylallenes) provided [4+2] cycloadducts. Reaction of benzene-bridged diallene bearing both a sulfinyl group and a phosphinyl group on the two allenyl groups was also described.     

Metal-free visible-light-promoted intermolecular [2+2]-cycloaddition of 3-ylideneoxindoles

The Rose Bengal sensitized intermolecular [2 + 2]-cycloaddition of 3-ylideneoxindoles for the synthesis of spirocyclic oxindoles was developed successfully under visible light irradiation conditions. The cycloaddition products were obtained in good yields (up to 93%) with excellent diastereoselectivity and regioselectivity by using a low loading of Rose Bengal (0.125 mol%) as a triplet sensitizer. This work demonstrates the potential benefits of Rose Bengal in visible light catalysis.