Formation Of Cycloadducts Research Articles

ChemInform Abstract: Formation of Cycloadducts with trans-Configurated Ester Groups from Nitrones and Dimethyl Maleate.

Abstract In the 1.3-dipolar cycloaddition of the cyclic nitrone 1c and the acyclic nitrones 8a-h 12a b with dimethyl maleate in refluxing chloroform not only the expected cycloadducts with cis-configuration of the two ester groups were formed but also such with trans-configuration. This phenomenon is not limited to chloroform, but was also observed in polar solvents as cyclohexane and n-hexane. However there is no clue for either a non-concerted reaction course or a subsequent conversion of the cis-products to trans-product in general. Rather conversion of dimethyl maleate to dimethyl fumarate seems to be responsible for the formation of the trans-substituted cycloadducts. This conversion can be induced by small quantities of N-alkylhydroxylamine formed from slight decomposition of nitrones under the reaction conditions or by small quantities of nitrone derivatives possessing a NOH moiety such as N-hydroxy enamine tautomers or nitrone dimers.

Stereo‐ and Regioselectivity in an Intramolecular Nitrone–Alkene Cycloaddition of Hept‐6‐enoses with a trans‐Acetonide Blocking Group

From sugar to cycloadduct: The effect of the trans-acetonide blocking group and the stereochemistry of the substituents on the regio- and stereoselectivity in the intramolecular nitrone-alkene cycloaddition (INAC) reaction of hept-6-enoses (see scheme) is reported and studied by using theoretical analysis.The positional effect of the trans-acetonide blocking group and the effect of the stereochemistry of the substituents on the regio- and stereoselectivity in intramolecular nitrone-alkene cycloaddition (INAC) reactions of hept-6-enoses are reported. Hept-6-enoses with a 2,3-trans-acetonide group were reacted with N-alkyl hydroxylamine to give a mixture of exo and endo cycloadducts (cyclohexanols and cycloheptanols, respectively). Complete formation of endo cycloadducts (cycloheptanols) was realized for the INAC reaction of hept-6-enoses containing a 3,4-trans-O-isopropylidene ring. Similarly, reaction of a hept-6-enose possessing a 4,5-trans-acetonide group surprisingly afforded exo cycloadducts (cyclohexanols) exclusively. The regio- and stereochemical outcomes of these reactions were rationalized on the basis of transition-state energies obtained by computation.

Synthesis of Highly Conjugated Arylpropenylidene-1,3-diazin-2-ones via Paterno–Büchi Reaction by Photoreaction of 5-Fluoro-1,3-dimethyluracil with 1-Methoxynaphthalenes

Abstract In contrast to photoreactions of 5-fluoro-1,3-dimethyluracil (5-FDMU) with various naphthalenes including 2-methoxynaphthalenes that proceeds in a manner to give ethenoquinazolines through 1,4-cycloaddition, UV-irradiation of a mixture of 5-FDMU and naphthalenes with a methoxy group at C-1 gave rise to the formation of novel cycloadducts, methyl 2-[(1E)-3-(5-fluoro-1,3-dimethyl-2-oxo-1,3-dihydropyrimidin-4-ylidene)prop-1-enyl]benzoates, derived from the novel aromatic Paterno–Büchi type cycloaddition, followed by a concomitant disruption of the initially formed oxetane moiety.

Hexafluorothioacetone‐Based Synthesis of Fluorinated Heterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Hexafluorothioacetone based synthesis of fluorinated heterocycles

Cycloadducts of hexafluorothioacetone (HFTA) were prepared in high yield by a CsF catalyzed reaction between readily available 2,2,4,4-tetrakis-(trifluoromethyl)-1,3-dithietane (as a source of HFTA) with conjugated electron-rich hydrocarbon dienes, such as cyclopentadiene, 2,3-dimethylbuta-1,3-diene, cyclohexa-1,3-diene or (1 Z,3 Z)-cyclohepta-1,3-diene. Cyclohexa-1,4- and (1 Z,5 Z)-cycloocta-1,5-dienes, also undergo the reaction with in situ generated HFTA, but form the products of insertion of HFTA into the C–H bond of the diene as a result of ene-reaction. The highly selective reaction of HFTA with (1 Z,3 Z,5 Z)-cyclohepta-1,3,5-triene and (1 Z,3 Z,5 Z,7 Z)-cycloocta-1,3,5,7-tetraene leads to the formation of cycloadducts derived from exclusive addition of thioacetone to the corresponding bicyclic isomers—bicyclo[4.1.0]hepta-2,4-diene or bicyclo[4.2.0]octa-2,4,7-triene, respectively. The corresponding cycloadducts of HFTA with 2,3-dimethylbutadiene-1,3-cyclohexa-1,3-cyclohexa-1,4-dienes and (1 Z,3 Z,5 Z)-cyclohepta-1,3,5-triene were also prepared by direct reaction of sulfur/hexafluoropropene/KF and the corresponding hydrocarbon substrate at 35–45 °C in DMF.

Positive Photocatalysis of a Diels−Alder Reaction by Quenching of Excited Naphthalene−Indole Charge-Transfer Complex with Cyclohexadiene

[reaction: see text] Naphthalene photo-catalyzes formation of cyclohexadiene-indole cycloadducts in a wavelength-dependent process. Steady-state irradiation and time-resolved fluorescence studies agree well with NP-InH ground-state charge transfer (CT) complexes as the key species responsible for the photo-catalyzed process.

Intramolecular Nitrilimine Cycloadditions to the Thiophene and the Furan Rings

The dipolarophilic behaviour of furan and thiophene rings have been exploited in the intramolecular cycloadditions of nitrilimines. These labile intermediates were generated from the corresponding hydrazonoyl chlorides by treatment with silver carbonate. The extent of formation of tricyclic cycloadducts was strongly dependent on the substitution pattern of the heteroaromatic ring, thus reflecting the HOMO-dipole controlled nature of the cycloaddition.

Synthesis and Diels-Alder Reactions of Dienophiles with Pentafluoro-λ6-sulfanyl (SF5) Moiety

This paper describes a convenient and efficient synthesis of new dienophiles containing a pentafluoro-λ 6 -sulfanyl moiety. These compounds react readily with both cyclic and aliphatic electron-releasing dienes, leading tothe formation of Diels-Alder cycloadducts.

Reaction of functionalized pyrone with N-benzylmaleimide: study of the relevant parameters for isolation of cycloadducts

New functionalized (ketone, ester or amide) pyrones derived from coumalic acid were synthesized either by a Friedel–Craft condensation of the diphenylether or by reactions with phenols and amines. The Diels–Alder (DA) cycloaddition of these pyrones with monofunctional maleimide the N-benzylmaleimide has been studied and two parameters, temperature and solvent effects, have been investigated to control the formation of cycloadduct containing CO2 bridge (CARAD) or decarboxylated cycloadducts (DECARAD). The pyrones and the cycloadducts were characterized by proton and carbon NMR, GC/MS and HPLC/MS. This work allowed the determination of the scope and limitation for the polyimide synthesis with bis-pyrones and bis-maleimides, which is under investigation.

Diels−Alder Reactions of 3-Substituted Coumarins in Water and under High-Pressure Condition. An Uncatalyzed Route to Tetrahydro-6H-benzo[c]chromen-6-ones

[reaction: see text] Diels-Alder reactions of 3-substituted coumarins 1a-g with methyl-1,3-butadienes 2a-c carried out in water alone and in CH2Cl2 under 9 kbar pressure are reported. In aqueous medium satisfactory results were obtained by operating at 150 degrees C, whereas under high pressure the cycloadditions were complete at 60-70 degrees C with excellent yields (85-95%). The reactions with isoprene (2b) always resulted in the exclusive formation of para cycloadducts, whereas with (E)-piperylene (2c) only ortho products were detected. The cycloaddition of 3-phenylsulfonylcoumarin (1a) with (E)-piperylene (2c) allowed the endo adduct to be obtained exclusively, whereas 3-carboxycoumarin (1b) reacted with 2c to give a mixture of the corresponding endo/exo adducts in a 58:42 ratio in water and in a 45:55 ratio under high-pressure condition.

Cover Picture: Cycloadditions and Methylene Transfer in Reactions of Substituted Thiocarbonyl S‐Methylides with Thiobenzophenone: A Computational Study (Eur. J. Org. Chem. 8/2005)

AbstractThe cover picture shows the potential energy diagram of methylene transfer from 4,4,5,5‐tetramethylcyclopentanethione S‐methylide to thiobenzophenone via a biradical intermediate which wins over a possible formation of regioisomeric cycloadducts. Methylene transfer reactions together with 1,3‐dipolar cycloadditions of other thiocarbonyl S‐methylides to thiones are described by R. Huisgen et al. on p. 1519 ff. DFT calculations on the mechanism of these reactions, concerted or stepwise, are reported by R. Sustmann et al. on p. 1505 ff.

Cycloaddition Reactions of Phosphorylated 1,2‐Diaza‐1,3‐butadienes with Olefins: Regioselective Synthesis of Pyridazine Derivatives

AbstractThe aza‐Diels–Alder reaction of 4‐phosphinyl‐ and 4‐phosphonyl‐1,2‐diaza‐1,3‐butadienes with styrene, cyclopentadiene, dihydrofuran and norbornadiene is reported. Monocyclic, bicyclic and polycyclic tetrahydropyridazines containing a phosphane oxide or a phosphonate substituent are obtained. The formation of cycloadducts can be explained by an endo transition state in the cycloaddition process of these heterodienes with styrene, cyclopentadiene, dihydrofuran, and by means of an exo transition state in the case of norbornadiene. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Absolute stereochemistry assignment of N‐phosphorylimine‐derived aza‐Diels‐Alder adducts with TDDFT CD calculations

N-phosphorylimines undergo Lewis acid-catalyzed Diels-Alder reactions with Danishefsky's diene. Application of the chiral catalyst zinc(II)-(S)-BINOL results in good-to-low asymmetric induction but poor chemical conversion. However, the absolute stereochemistry of novel aza-Diels-Alder cycloadducts, such as diethyl 4-oxo-2-phenyl-3,4-dihydropyridin-1(2H)-ylphosphonate, can be determined using circular dichroism (CD). Comparison between experimental and TDDFT-calculated CD spectrum shows that use of the (S)-catalyst results in predominant formation of the (6R) cycloadducts.

On the 1,3-dipolar cycloaddition reactions of indenone with N–N–C dipoles: density functional theory calculations

Density functional theory (DFT) calculations at the B3LYP/6-311G ∗ theoretical level have been performed to study the 1,3-dipolar cycloaddition (1,3-DC) reactions between indenone ( 1) and different 1,3-dipoles (diazomethane and N-methyl C-methoxy carbonyl nitrilimine, compounds 2 and 3, respectively). The geometrical and energetic properties were analysed for the different reactives, transition states and cycloadducts formed (compounds 4– 11). The reactions proceed in the gas-phase by an asynchronous concerted mechanism, yielding different regiochemistry dependent on the 1,3-dipole chosen, although with dipole 3 some degree of synchrony was found in the formation of cycloadduct 5. The 1,3-DC between 1 and 3 was regioselective, being the cycloadduct 11 favoured against 9. The NMR chemical shift parameters (GIAO method) were also calculated for the reactives and cycloadducts.

Preparation and cycloaddition reactions of enantiopure 2-(N-acylamino)-1,3-dienes for the synthesis of octahydroquinoline derivatives.

Stille, Suzuki-Miyaura, and Sonogashira cross-coupling reactions were carried out with a glutarimide-derived vinyl phosphate, bearing a chiral auxiliary on the N atom, to prepare enantiopure 2-(N-acylamino)-1,3-dienes as partners in Diels-Alder reactions. The cycloadditions were performed with various dienophiles under thermal conditions, with or without Lewis acids. With maleimides, the preferential formation of endo cycloadducts was observed, whereas with acrylamides the exo approach prevailed. Furthermore, in the latter case, 6-substitued octahydroquinolinones were obtained in accordance with the predicted regioselectivity. Since diastereopure compounds were in all cases obtained either by chromatography or by crystallization, and because of the easy access to a variety of boronic acids, to be used in the coupling step, this methodology is useful for the short synthesis of differently substituted, enantiopure octahydroquinolinones amenable to further transformation into decahydroquinolines possessing interesting biological activities.

Organocatalysts Promote Enantioselective 1,3‐Dipolar Cycloadditions of Nitrones with 1‐Cycloalkene‐1‐carboxaldehydes

AbstractIn the presence of enantiopure organocatalysts, 1‐cycloalkene‐1‐carboxaldehydes and various nitrones furnished fused isoxazolidines. Thus, some chiral pyrrolidinium salts catalyzed the formation of such cycloadducts in high diastereo‐ and enantioselectivity (up to 92% ee). The predominant diastereomer, the exo one, was mostly obtained in excellent diastereoselectivity (> 99:1 dr). Furthermore, after recrystallization of one of the cycloadducts, this was obtained enantiomerically pure (> 99% ee). The absolute configuration of one of the cycloadducts was determined. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Photo aldol reactions with 5-methoxyoxazoles: Highly regio- and diastereoselective synthesis of α-amino β-hydroxy carboxylic acid derivatives

A versatile route to derivatives of α-amino β-hydroxy carboxylic acids, either with tertiary (from a corresponding glycine equivalent) or a quaternary α-carbon center is described. The key reaction is the cycloaddition of electronically excited carbonyl compounds (aromatic and aliphatic aldehydes, respectively) to oxazoles. To make the products hydrolytically more labile, a methoxy substituent at position C-5 was introduced leading to the formation of cycloadducts with an orthoester substructure. The photocycloaddition, either with triplet excited (aromatic) carbonyls or with singlet excited (aliphatic) carbonyls, led to the formation of mixtures of endo- and exo-diastereoisomers with moderate to very high exo-selectivities. The 4-unsubstituted 5-methoxyoxazole 1 (glycine equivalent) gave the [2 + 2]-adducts 3a–3f with aldehydes 2a–2f in high yields and excellent diastereoselectivities. Hydrolysis of these compounds resulted in the α-amino β-hydroxy esters 4a–4f with preferred erythro (S*,S*) configuration. As an extension of this process, 4-alkylated 5-methoxyoxazoles 5a–5f were applied as alkene components and the corresponding cycloadducts with benzaldehyde 6a–6f were obtained. Again, the exo-diastereoisomers were formed as the major products in diastereoselectivities from 73:27 (exo:endo) up to >95:5. Hydrolysis of these adducts resulted in the formation of α-amino β-hydroxy esters 7a–7f with like (S*,S*) configuration of the major diastereoisomers.Key words: photo aldol reaction, oxazoles, oxetanes, photocycloaddition, amino acids, hydroxy acids.

2 + 3] Cycloaddition of C,C,N‐triphenylnitrone to trans‐substituted nitroethylenes in the light of an AM1 and AM1/COSMO computational study

AbstractAM1 calculations suggest that the [2 + 3] cycloaddition of triphenylnitrone 1 to nitroalkenes 2a–c in the gas phase takes place in a concerted manner. However, the azolidine ring bonds C3—C4 and O1—C5 are not formed fully synchronously. Kinetic factors favor the formation of cycloadducts with nitro group in position C‐4 of the azolidine ring (path A). Introduction of toluene, acetone or acetonitrile as a reaction medium increases the activation barriers for both regioisomeric paths. Simultaneously, the energy profiles for path A undergo qualitative change. In this case, two transition states and an intermediate with zwitterionic character were localized by means of the AM1/COSMO method. Copyright © 2003 John Wiley & Sons, Ltd.

Isolation of Methyl (RS)‐1‐tert‐Butoxycarbonyl‐3‐cyanomethyl‐1,2‐dihydro‐2‐oxo‐5H‐pyrrole‐5‐ carboxylate, the Key‐Intermediate in Base‐Catalyzed Formation of Racemic Products by 1,3‐Dipolar Cycloadditions to Methyl (S)‐1‐tert‐Butoxycarbonyl‐3‐ [(E)‐cyanomethylidene]‐2‐pyrrolidinone‐5‐carboxylate.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Isolation of methyl (RS)‐1‐tert‐butoxycarbonyl‐3‐cyanomethyl‐1,2‐dihydro‐2‐oxo‐5H‐pyrrole‐5‐carboxylate, the key‐intermediate in base‐catalyzed formation of racemic products by 1,3‐dipolar cycloadditions to methyl (S)‐1‐tert‐butoxycarbonyl‐3‐[(E)‐cyanomethylidene]‐2‐pyrrolidinone‐5‐carboxylate

AbstractCycloadditions of various 1,3‐dipoles to methyl (S)‐1‐tert‐butoxycarbonyl‐3‐[(E)‐cyanomethylidene]‐2‐pyrrolidinone‐5‐carboxylate (9) were studied. Reactions of 9 with diazomethane (10) and 2,4,6‐trimethoxy‐benzonitrile oxide (11), carried out under neutral conditions, gave the corresponding optically active spiro compounds 16‐18 with low diastereoselectivity (20‐30% diastereomeric excess). On the other hand, reactions of 9 with nitrile oxide 11 and nitrile imines 14, 15, carried out in the presence of a base, afforded racemic pyrazolo and isoxazolo fused 2‐pyrrolidinones 21‐23 in 82‐86% diastereomeric excess. Optically active dipolarophile 9 was isomerized in the presence of basic alumina to give methyl (RS)‐1‐tert‐butoxy‐carbonyl‐3‐cyanomethyl‐1,2‐dihydro‐2‐oxo‐5H‐pyrrole‐5‐carboxylate (19). Treatment of the racemic dipolarophile 19 with dipoles 11 and 14, afforded fused 2‐pyrrolidinones 23 and 21. These observations support compound 19 as the key‐intermediate in the formation of racemic cycloadducts 21‐23.