Ene Product Research Articles

Ene reactions of acyl nitroso intermediates with alkenes and their halocyclization

Highly reactive acyl nitroso intermediates were formed in situ by transition metals-catalyzed hydrogen peroxide oxidation of hydroxamic acids 1a– b and these transient species trapped with alkenes 2a– c to afford the corresponding ene products 3a– d and 4b up to 91% yield, and halocyclization of 3d gave substituted oxazolidinone 5a in 77% yield.

Ene reaction of allylbenzene and N-methylmaleimide in subcritical water and ethanol

Ene reaction of allylbenzene and N-methylmaleimide was studied in water and ethanol solvents at subcritical temperatures (220–310 °C). Subcritical water was inappropriate for this reaction, because it rapidly hydrolyzed N-methylmaleimide. Subcritical ethanol was found to be a very promising solvent. The highest ene product yield in ethanol reached 40% in 480 min, and the highest trans-selectivity was 92%. The yields in pure ethanol were comparable to those in 1,2,4-trichlorobenzene with 10% hydroquinone added as a polymerization inhibitor. Addition of hydroquinone had a negligible effect on the yield in ethanol, suggesting that the solvent ethanol itself acts as an inhibitor of the side reactions. It is also expected that the polar environment and the high vapor pressure of ethanol favored pericyclic association between the apolar starting compounds.

Efficient Synthesis of the Azaspirocyclic Core Structure of Halichlorine and Pinnaic Acid by Intramolecular Acylnitroso Ene Reaction.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient synthesis of the azaspirocyclic core structure of halichlorine and pinnaic acid by intramolecular acylnitroso ene reaction.

[reaction: see text] A new efficient strategy for the construction of the 6-azaspiro[4.5]decane ring system was developed using intramolecular ene reaction of the acylnitroso compound. The spirocyclic ene product obtained as a single diastereomer was subsequently subjected to highly stereoselective ethynylation, leading to the azaspirodecane core of halichlorine and the pinnaic acids.

Intrazeolite Photo‐oxygenation of (R)‐(‐)‐α‐Phellandrene.

AbstractFor Abstract see ChemInform Abstract in Full Text.

(2,5)-Ene cyclization catalyzed by mesoporous solid acids: isotope labeling study and ab initio calculation for continuum from concerted to stepwise ene mechanism.

(2,5)-Ene reactions catalyzed by mesoporous solid acids are reported from the mechanistic point of view. The continuum (2,5)-ene mechanism from the concerted to the cationic cyclization followed by 1,2-hydride shift is evaluated. The solid-acid-catalyzed cyclization of the oxonium ion intermediate 4 derived from cyclic allylic lactol ether 3 bearing allylic hydroxy group affords the (2,5)-ene product as the enol form, eventually tautomerizing to the corresponding aldehyde 6. The continuum from the concerted to stepwise mechanism is experimentally and theoretically verified in the present ene cyclization of the oxonium ion intermediate such as 4. The stepwise cyclization leading to aldehyde 6 is thus shown to associate with the concerted version as a result of the stabilization of the beta-hydroxycarbenium ion intermediate.

Electronic effects in the regioselectivity of the singlet oxygen and 4-methyl-1,2,4-triazoline-3,5-dione ene reactions with isobutenylarenes

The regioselectivity of the ene pathway in the photooxidation of several 1-aryl-2-methylpropenes, as probed by stereoselective deuterium-labeling, depends on the electronic nature of the para phenyl-substituents. The reaction of the same array of alkenylarenes with 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) gives ene products with an impressive >97% allylic hydrogen abstraction from the more substituted side of the alkene.

The ene reactions of nitroso compounds involve polarized diradical intermediates.

The ene reactions of nitroso compounds were studied with B3LYP/6-31G* geometry optimizations and energy calculations, along with single point energy evaluations using CASPT2/6-31G** and UCCSD(T)/6-311+G* methods. Reactions of HNO with propene and of MeNO and p-NO2C6H4NO with propene or substituted alkenes were also studied. The reaction mechanism is stepwise and involves a polarized diradical intermediate. The electronic structure of this intermediate is between that of a closed shell polar species and that of a pure diradical, and it is stabilized by polar solvents. A weak C-N bonding interaction combined with a CH-O hydrogen bond leads to heightened barriers to rotation about formally single bonds compared to conventional diradicals. Consequently, rotation is slower than hydrogen abstraction and cyclization to form an aziridine N-oxide. This aziridine N-oxide does not lead to ene products without subsequent ring opening but provides a mechanism for the RNO moiety to translate from one end of the alkene to the other. B3LYP calculations are also able to reproduce kinetic isotope effects and regioselectivity.

Ene reaction of singlet oxygen, triazolinedione, and nitrosoarene with chiral deuterium-labeled allylic alcohols: the interdependence of diastereoselectivity and regioselectivity discloses mechanistic insights into the hydroxy-group directivity.

The ene reaction of singlet oxygen ((1)O(2)), triazolinedione (TAD), and nitrosoarene, specifically 4-nitronitrosobenzene (ArNO), with the tetrasubstituted 1,3-allylically strained, chiral allylic alcohol 3,4-dimethylpent-3-en-2-ol (2) leads to the threo-configured ene products in high diastereoselectivity, a consequence of the hydroxy-group directivity. Hydrogen bonding favors formation of the threo-configured encounter complex threo-EC in the early stage of ene reaction. For the analogous twix deuterium-labeled allylic alcohol Z-2-d(3), a hitherto unrecognized dichotomy between (1)O(2) and the ArNO and TAD enophiles is disclosed in the regioselectivity of the tetrasubstituted alcohol: Whereas for ArNO and TAD, hydrogen bonding with the allylic hydroxy group dictates the regioselectivity (twix selectivity), for (1)O(2), the cis effect dominates (twin/trix selectivity). From the interdependence between the twix/twin regioselectivity and the threo/erythro diastereoselectivity, it has been recognized that the enophile also attacks the allylic alcohol from the erythro pi face without assistance by hydrogen bonding with the allylic hydroxy functionality.

Efficient pi-facial control in the ene reaction of nitrosoarene, triazolinedione, and singlet oxygen with tiglic amides of the bornane-derived sultam as chiral auxiliary: an economical synthesis of enantiomerically pure nitrogen- and oxygen-functionalized acrylic acid derivatives.

The ene reaction of 4-nitronitrosobenzene (ArNO), N-phenyl-1,2,4-triazoline-3,5-dione (PTAD), and singlet oxygen (1O2) with the optically active tiglic-acid derivatives of Oppolzer's bornane-derived sultam affords the respective ene products regioselectively in excellent diastereoselectivity (de up to 99%) and in good yield (55-90%). The enophiles ArNO and PTAD give with the methyl-substituted substrate exclusively the like-configured ene adduct, while 1O2 leads to an 83:17 diastereomeric mixture. With the sterically more demanding isopropyl-substituted derivative even the smallest enophile 1O2 forms exclusively the like diastereomer. The high diastereoselectivity is rationalized in terms of the proper conformational alignment of the substrate and a preferred enophilic attack from the C(beta)-re face of the double bond. This concept offers an efficient synthetic route to enantiomerically pure nitrogen- and oxygen-functionalized acrylic acid derivatives.

Practical Carbonyl‐Ene Reactions of α‐Methylstyrenes with Paraformaldehyde Promoted by a Combined System of Boron Trifluoride and Molecular Sieves 4A.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Intrazeolite photo-oxygenation of (R)-(-)-α-phellandrene

Thionin-sensitised intrazeolite photo-oxygenation of ( R)-(-)-α-phellandrene affords (1 S,5 R)-5-(1-methylethyl)-2-methylidene-3-cyclohexen-1-yl hydroperoxide as the major ene product. This can be easily reduced with triphenylphosphine to the natural product trans-yabunikkeol.

Practical carbonyl-ene reactions of alpha-methylstyrenes with paraformaldehyde promoted by a combined system of boron trifluoride and molecular sieves 4A.

[reaction: see text] A combined system of boron trifluoride and molecular sieves is an efficient promoter for the carbonyl-ene reaction of alpha-methylsyrenes with paraformaldehyde. The coexistence of BF3 x OEt2 and molecular sieves 4A is essential for obtaining high yields of ene products.

Disparate Roles of Chiral Ligands and Molecularly Imprinted Cavities in Asymmetric Catalysis and Chiral Poisoning

The activation of molecularly imprinted metal complexes generates Lewis acid catalysts for the ene reaction, each of which contains a chiral diphosphine ligand and a chiral BINOL-shaped cavity. Poisoning experiments with (R)- and (S)-BINAM indicate that while the chiral cavity can differentiate the chiral poisons, it is the chiral diphosphine ligand which controls the enantioselectivity of the ene product.

Example of a Thermodynamically Controlled Reaction on a Semiconductor Surface: Acetone on Ge(100)-2 × 1

The adsorption of acetone on the Ge(100)-2 × 1 surface has been investigated using multiple internal reflection infrared spectroscopy and density functional theory quantum chemistry calculations and was found to be under thermodynamic control at room temperature. Acetone undergoes attachment at the carbonyl oxygen with loss of an α hydrogen at room temperature on the Ge(100)-2 × 1 surface to form an enol-like adduct. This so-called ene reaction has not been seen on the Si(100) surface, on which the reaction of acetone is under kinetic control and instead a less thermodynamically favored [2 + 2] addition across the carbonyl bond is observed. At low temperature, acetone adsorbs via dative-bond formation with the surface, which we find to be too weak to remain at room temperature in contrast to the stronger dative bonds formed by amines on the Si(100) and Ge(100) surfaces. There is evidence that the acetone ene product may undergo oxygen migration and insertion into Ge−Ge bonds, especially at elevated surface temperatures. Whereas the reactions of organics on Si(100)-2 × 1 are typically under kinetic control, thermodynamic control on the Ge(100)-2 × 1 surface is made possible by the reversibility of weak surface adsorption. The strategic use of thermodynamically controlled reactions on the Ge(100)-2 × 1 surface represents a new and potentially powerful approach for the selective formation of organic-functionalized semiconductor surfaces.

Photoinduced Electron-Transfer Oxidation of Olefins with Molecular Oxygen Sensitized by Tetrasubstituted Dimethoxybenzenes: A Non-Singlet-Oxygen Mechanism

α-Methylstyrene (1) was photo-oxidized in the presence of a series of alkylated dimethoxybenzenes as sensitizers in an oxygen-saturated MeCN solution to afford the cleaved ketone 2, epoxide 3, as well as a small amount of the ene product 4 in ca. 1 : 1 : 0.04 ratio. The relative rate of conversion was well-correlated with the fluorescence quantum yield of sensitizers. Thus, a non-singlet-oxygen mechanism is proposed, in which an excited sensitizer is quenched by (ground-state) molecular oxygen to produce a sensitizer radical cation and a superoxide ion (O), the former of which oxidizes the substrate, while the latter reacts with the resulting olefin radical cation (1+.) to give the major oxidation products. Photodurability of such electron-donating sensitizers is dramatically improved by substituting four aromatic H-atoms in 1,4-dimethoxybenzene with Me or fused alkyl groups, which provides us with an environmentally friendly, clean method of photochemical functionalization with molecular oxygen, alternative to the ene reaction via singlet oxygenation.

Photoinduced electron transfer oxidation of α-methylstyrene with molecular oxygen sensitized by dimethoxybenzenes: a non-singlet-oxygen mechanism

α-Methylstyrene ( 1 ) was photooxidized with oxygen in the presence of a series of alkylated dimethoxybenzenes as a sensitizer in acetonitrile, affording the cleaved ketone ( 2 ), epoxide ( 3 ) as well as a small amount of the ene product ( 4 ) in ca. 1:1:0.04 ratio. A non-singlet-oxygen mechanism is proposed, in which an excited sensitizer is quenched by oxygen to produce a sensitizer radical cation and a superoxide ion (O 2 −), the former of which oxidizes 1 , while O 2 − reacts with the resulting 1 + to give the major oxidation products.

ChemInform Abstract: Steric and Conformational Control of the Regioselectivities in the Ene Reaction with Trisubstituted Cycloalkenes: Comparison of the Enophiles Singlet Oxygen, Triazolinedione, and Nitrosoarene.

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Adducts of sila-, germa-, and stannaethenes Me2E=C(SiMe3)2 (E = Si, Ge, Sn) with anthracene: syntheses, structures, thermolyses

The [4 + 2] cycloadducts of Me2E=C(SiMe3)2 (E = Si, Ge, Sn) and anthracene are prepared by reaction of an excess of anthracene in benzene with the [2 + 2] cycloadduct of Me2Si=C(SiMe3)2 and Ph2C=NSiMe3 at 130°C, with Me2Ge(OPh)-CLi(SiMe3)2 at 100°C, and with Me2SnBr-CNa(SiMe3)2 at 80°C, respectively. The mentioned adducts act as sources for the ethenes Me2E=C(SiMe3)2 above 100°C, the intermediate formation of which has been demonstrated by trapping experiments with 2,3-dimethylbutadiene (formation of a [4 + 2] and an ene reaction product). The half life time of the anthracene adducts with E = Si, Ge, and Sn in the presence of DMB (= 2,3-dimethylbutadiene) in benzene on thermolysis at 130°C (first order reactions) is found to be 141, 12, and 0.3 h, respectively. In the absence of DMB, thermolysis of the cycloadducts leads in benzene as reaction medium exclusively to the dimers of the Me2E=C(SiMe3)2 intermediates. In toluene as reaction medium ene products of Me2E=C(SiMe3)2 are observed in addition to the dimers. The ene products are not isolable as such, but only after migration of the Me2E-CH(SiMe3)2 substituents. The formed derivatives C6H5CH2EMe2CH(SiMe3)2 of toluene in part give a second ene reaction with another Me2E=C(SiMe3)2 molecule. X-ray structure analyses of the mentioned sources in fact prove the latter to be normal [4 + 2] cycloadducts of Me2E=C(SiMe3)2 and anthracene.Key words: silaethene, germaethene, stannaethene, [4 + 2] anthracene adducts, [4 + 2] cycloadditions and reversions, ene reactions, X-ray structure analyses.

Steric and conformational control of the regioselectivities in the ene reaction with trisubstituted cycloalkenes: comparison of the enophiles singlet oxygen, triazolinedione, and nitrosoarene

The nitrosoarene ene reaction with the cycloalkenes 1-3 and E-4 proceeds in high twix regioselectivity to afford the hydroxylamine ene products 1a-4a (twix) and 1b-4b (twin, except far E-4 twix). Steric interactions in the enophile attack are responsible for the skew trajectory of the nitrosoarene enophile. For Z-1-methylcyclooctene (Z-4), twin abstraction dominates, caused by conformational constraints (transannular interactions) in the hydrgogen-atom abstraction. The balance between these steric and conformational factors dictates the regioselectivity in the ene reaction