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.     

Syntheses of substituted and fused furo[3,2-c]pyridines

Department of Organic Chemistry, Slovak Technical University, 812 37 Bratislava, Slovak Republic. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1390–1392, October, 1995. Original article submitted August 24, 1995.     

Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade

A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].     

Furfuryl vinyl ethers in [4+2]-cycloaddition reactions

For the first time [4+2]-cycloaddition reactions were carried out between furfuryl vinyl ethers and typical dienophiles and heterodienes proceeding in uncatalyzed conditions and resulting in previously unknown heterocyclic systems containing either free vinyloxy groups or furfuryl substituents. With maleic anhydride and maleimide furfuryl vinyl ethers afforded 1-(vinyloxyalkyl)tricyclodec-8-ene-3,5-diones in up to 72% yields, and with N-benzylideneaniline or acrolein the corresponding functionally substituted tetrahydroquinolines (yield up to 65%) or 3,4-dihydropyrans (yield 23–50%) were obtained.     

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.     

Isomerization of 5-(2H-Azirin-2-yl)oxazoles: An Atom-Economic Approach to 4H-Pyrrolo[2,3-d]oxazoles

An atom economical method for the preparation of variously substituted 4H-pyrrolo[2,3-d]oxazoles was developed on the basis of thermal isomerization of 5-(2H-azirin-2-yl)oxazoles. The latter were prepared by Rh₂(oct)₄ catalyzed reaction of 2-(3-aryl/heteroaryl)-2-diazoacetyl-2H-azirines with a set of substituted acetonitriles, benzonitriles, acrylonitrile and fumaronitrile. According to DFT calculations the transformation of 5-(2H-azirin-2-yl)oxazole to 4H-pyrrolo[2,3-d]oxazole occurs through the nitrenoid-like transition state to give a 3aH-pyrrolo[2,3-d]oxazole intermediate, followed by 1,5-H-shift.     

Wavelength-dependent selectivity in [4 + 4]-cycloaddition reactions

Selective excitation of a variety of anthracene derivatives in the presence of anthracene led to the formation of only the cross-cyclomer products, while irradiating these mixtures at wavelengths where anthracene also absorbs led to both dianthracene and the mixed cyclomers being formed. This method was shown to be general, so long as the chromophore was inert toward forming its homodimer and could be irradiated at wavelengths at which anthracene does not absorb.     

Highly regioselective construction of spirocycles via phosphine-catalyzed [3 + 2]-cycloaddition

A direct entry to spirocycles with low to moderate regioselectivity was achieved by triphenylphosphine-catalyzed [3 + 2]-cycloaddition of active exo-methylenecycles (1) and ethyl 2,3-butadienoate (2). The regioselectivity of the reaction was greatly improved by using the bulky tert-butyl ester of the 2,3-butadienoate (5). The regioselectivity of the reaction was further enhanced by using the tert-butyl 2-butynoate as the substrate. This protocol provided an efficient entry to the skeleton of spirocarbocycles, especially spiro[4.n]alkanes.     

Synthesis of substituted pyrano[3,2-c]pyridines via Diels-Alder reaction of 3-methylenepyridin-4-one

On heating, the di-Boc-pyridin-4-one derivative 7 gave an unstable 3-methylenepyridin-4-one intermediate 3, which underwent a rearomatising Diels-Alder cycloaddition with activated alkenes to give substituted pyrano[3,2-c]pyridines in moderate yields.     

Photoinduced [4 + 4] cycloadditions of o-quinones with oxazoles

[reaction: see text] Photocycloadditions of 9,10-phenanthraquinone (PQ) with oxazoles (1a and 1b) gave [4 + 4] products 2 with the O=C-C=O functionality in PQ and the 2-azadiene moiety in oxazole as 4pi addends. Photoreactions of 1-acetylisatin (IS) with 1a, 1c, and 1d gave [4 + 4] product A, which underwent further [2 + 2] reactions with another (3)IS to furnish 5. These regioselective and diastereoselective [4 + 4] photocycloadditions are rationalized by the intervening of the key conformers for ISC and bond formation of the most stable 1,6-diradical intermediates.     

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.     

On the [4+2]-cycloaddition reaction of levoglucosenone with piperylene

The Diets-Alder reaction of levoglucosenone with piperylene catalyzed by ZnCl₂ proceeds regio- and stereoselectively to give thesin-cis-adduct3; the thermal reaction yields an epimeric mixture of compound3 withsin-trans-adduct4 in the ratio of 4 : 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2584–2585, October, 1996.     

Synthesis of C-arylglycosides via Ru(II)-catalyzed [2 + 2 + 2] cycloaddition

In the presence of catalytic amounts of Cp*RuCl(cod), the cycloaddition of 1,6-diynes with various C-alkynylglycosides proceeded at ambient temperature to afford C-arylglycosides in 46-93% yields.     

Synthesis of substituted 2-alkyl(aryl)thio-3-cyanopyridines and 3-aminothieno[2,3-b]pyridines

The alkylation of 6-methyl-4-methoxymethyl-3-cyano-2-(1H)pyridinethione by halogen derivatives in the presence of KOH proceeds regioselectively with the formation of S-alkyl derivatives. By cathodic electrolysis of the thiols in the presence of 6-methyl-4-methoxymethyl-2-chloro-3-cyanopyridine, 2-arylthiopyridines are obtained. By Thorpe-Ziegler cyclization of 2-alkylthiopyridines having an ctive methylene group, 2-aminothieno[2,3-b]pyridines have been synthesized.Kuban State Technological University, Krasnodar, 350072. N. D. Zelinskii Institute of Organic Chemistry, Moscow 117913. Southern Branch of Association Rosvuznauka, Krasnodar, 350072. Translated from Khimiya Geterotsiklicheskikh Soedinenii, NO. 10, pp. 1432–1437, October, 1996. Original article submitted April 2, 1996; revision submitted August 20, 1996.     

Synthesis of 2-indanones via [4 + 1] annulation reactions of (trialkylsilyl)arylketenes

[reaction: see text] (Trialkylsilyl)arylketenes combine with (trimethylsilyl)diazomethane in a new [4 + 1] annulation process leading to 2-indanone derivatives. The (trialkylsilyl)arylketene annulation substrates are available via the photochemical Wolff rearrangement of alpha-silyl-alpha-diazo ketones, which are themselves prepared by silylation of the corresponding diazo ketones. The mechanism of the annulation reaction is proposed to involve the formation of a 2,3-bis(silyl)cyclopropanone, which is in equilibrium with an oxyallylic cation. Electrocyclic closure of this intermediate forms the new cyclopentenone ring.     

Synthesis of polynuclear aromatic compounds through net [5+5]-cycloaddition of 2-alkynylarylcarbene complexes and enyne-aldehyde derivatives

Coupling of o-alkynylphenylcarbene complexes and -o-alkynylheteroarene carboxaldehydes leads to heterocycle annulated phenanthrene derivatives.     

Synthesis of azapolycyclic systems via the intramolecular [4 + 2] cycloaddition chemistry of 2-(alkylthio)-5-amidofurans

A series of 2-(methylthio)-5-amidofurans containing tethered unsaturation were prepared via the reaction of dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) with beta-alkoxy-gamma-dithiane amides 13-16 and 27-32 in 40-70% yield. Thermolysis of these furans resulted in an intramolecular Diels-Alder reaction (IMDAF). With the exception of 45 and 46, the oxa-bridged cycloadducts could not be isolated but immediately underwent a 1,2-methylthio shift to form bicyclic lactams in 60-100% yield. It was determined that incorporation of the amido carbonyl in the tether allowed the IMDAF reaction to proceed at a lower temperature. A dramatic example of this is seen in the IMDAF reaction of furan 35, in which the presence of an amido carbonyl as part of the dienophile tether, as opposed to the annealed ring (66) or the lack of a carbonyl (67), was necessary for the cycloaddition to occur. Furan 37, annealed to an azepine ring, underwent the IMDAF reaction at or below room temperature. To identify structural features that promote the IMDAF reaction, a computational study was undertaken. Ground-state and transition-state energies were calculated for furans 17, 33, 37, and 64 using the Becke 3LYP/6-31G model. The theoretical results were in good agreement with those observed. The results indicate that the incorporation of an amide carbonyl as part of the tether system works to place the dienophile in closer proximity to the furan ring, thereby lowering the activation energy needed to reach the transition state.     

An expeditious stereoselective synthesis of natural (-)-Cassine via cascade HWE [3 + 2]-cycloaddition process

l-Rhamnose is transformed to (-)-Cassine via a remarkable four step one pot reaction. The Horner-Wadsworth-Emmons [3 + 2]-1,3-dipolar cycloaddition reaction cascade is the pivotal step in this reaction sequence and makes the synthesis highly efficient.