Sigmatropic Hydrogen Migrations Research Articles

Molecular Modeling of Photochemical and Thermal Sigmatropic Hydrogen Migration in the Formation of Tautomeric Forms of Some Biomolecules in DNA

Molecular Modeling of Photochemical and Thermal Sigmatropic Hydrogen Migration in the Formation of Tautomeric Forms of Some Biomolecules in DNA

ChemInform Abstract: An Unexpected Double Diels—Alder Reaction of (E)‐2‐Bromo‐4‐aryl‐1,3‐pentadiene Involving [1,5]‐Hydrogen Migration and HBr Elimination: Synthesis of Bicyclo[2.2.2]octene Derivatives.

An unexpected double Diels-Alder (DDA) reaction of (E)-2-bromo-4-aryl-1,3-pentadiene was developed and resulted in a series of butterfly-like bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for a metal catalyst. The proposed mechanism involves a [1,5]-sigmatropic hydrogen migration and HBr elimination. Through this decisive [1,5]-hydrogen shift step, the electronic properties and steric hindrance of the conjugated diene substrate are completely altered and the DDA reaction of this potential diene synthon is successfully achieved.

An unexpected double Diels-Alder reaction of (E)-2-bromo-4-aryl-1,3-pentadiene involving [1,5]-hydrogen migration and HBr elimination: synthesis of bicyclo[2.2.2]octene derivatives.

An unexpected double Diels-Alder (DDA) reaction of (E)-2-bromo-4-aryl-1,3-pentadiene was developed and resulted in a series of "butterfly-like" bicyclo[2.2.2]octene derivatives in moderate to good yields without the need for a metal catalyst. The proposed mechanism involves a [1,5]-sigmatropic hydrogen migration and HBr elimination. Through this decisive [1,5]-hydrogen shift step, the electronic properties and steric hindrance of the conjugated diene substrate are completely altered and the DDA reaction of this potential diene synthon is successfully achieved.

NHC-Stabilized 1-Hydro-1H-borole and Its Nondegenerate Sigmatropic Isomers

Electrophilic quenching of a carbene-stabilized π-boryl anion with the Brønsted acid Et(3)NHCl provides a convenient synthetic route to the parent NHC-stabilized 1-hydroborole, which isomerizes to the corresponding 3-hydroborole via two successive nondegenerate [1,5]-sigmatropic hydrogen migrations. Molecular structures of both isomers have been determined by X-ray crystallography.

A pericyclic cascade to the stereocontrolled synthesis of 9-cis-retinoids

A domino reaction that is pericyclic in nature is thought to be triggered upon treatment of alkenynol 10 with arylsulfenyl chlorides. The process comprises an ordered sequence of sigmatropic rearrangements: a reversible [2,3]-allyl sulfenate to allyl sulfoxide shift, followed by a [2,3]-propargyl sulfenate to allenyl sulfoxide rearrangement, and last a stereodifferentiating [1,5]-sigmatropic hydrogen migration leading to polyene 13. The occurrence of the C7 to C11 hydrogen migration has been demonstrated by labeling experiments. The double diastereoselection of the [1,5]-sigmatropic hydrogen shift to afford a single isomer of the final polyene 13 is thought to arise from a combination of the electronic effect of the sulfoxide at one terminus, and the steric effect imparted by the bulky trimethylcyclohexenyl substituent at the other terminus. The overall process thus constitutes a stereoselective synthesis of an E,Z,Z-triene fragment from an alkenynol and, in particular, a retinoid with the 7E,9Z,11Z,13E configuration on the conjugated polyenic side chain. Application of this method to the synthesis of retinoids, including labeled analogues, is straightforward.

Theoretical investigation of the [1,2]-sigmatropic hydrogen migration in the mechanism of oxidation of 2-aminobenzoyl-CoA by 2-aminobenzoyl-CoA monooxygenase/reductase.

The flavin hydroperoxide at the active site of the mixed-function oxidase 2-aminobenzoyl-CoA monooxygenase/reductase (Azoarcus evansii) transfers an oxygen to the 5-position of the 2-aminobenzoyl-CoA substrate to provide the alkoxide intermediate II(-). Hydrogen migration from C5 to C6 follows this monooxygenation. The nature of the monooxygenation intermediate and plausible competing reactions leading to hydrogen migration have been considered. Ab initio molecular orbital theory has been used to calculate structures and electron distributions in intermediate and transition state structures. Electrostatic potential surface calculations establish that the transition state and product, associated with the C5 to C6 hydrogen transfer, are stabilized by electron distribution to the benzoyl-CoA thioester carbonyl oxygen. This is not so for the transition state and product associated with hydrogen transfer from C5 to C4. The activation energy for the 5, 6-shift is 2.5 kcal/mol lower than that for the 5,4-shift. In addition, the product of the hydrogen 5,6-shift is more stable than is the product of the hydrogen 5,4-shift, by approximately 6 kcal/mol. These results explain why only the shift of hydrogen from C5 to C6 is observed experimentally. Oxygen transfer and hydrogen migration almost coincide in the gas phase (activation energy of approximately 0.6 kcal/mol, equivalent to a single bond vibration). Enzymatic formation of alkoxide II(-) requires its stabilization; thus, the rate constant for its breakdown would be slower than in the gas phase.

Studies of vitamin D (calciferol) and its analogs. 36. Hydroxyl-directing effects on [1,7]-sigmatropic hydrogen migrations

Etude stereomecanistique de la reaction du titre (reaction pericyclique a 8 electrons) pour des analogues du cis-isotachysterol portant un groupement hydroxyallylique en C 4 au lieu de C 1

Thermolysis of unsymmetrically substituted vinylcyclopropanes. Regarding the effect of oxygen substituents on the site-selectivity of homo-[1,5]-sigmatropic hydrogen migrations

Thermal rearrangement of compounds 1, 8–11, and 20 results, in each case, in the exclusive migration of the hydrogen (HΛ) not associated with the oxygen substituent. On the other hand, thermolysis of 19, 22, and 23 provides, in each case, a mixture of the two possible sigmatropic rearrangement products. Similar bond reorganization of the hydrocarbon 21 affords the dienes 27 and 28 (98:2, respectively). On the basis of these results, along with those reported earlier, it is proposed that in the transition states for these rearrangements (a) there is an accumulation of electron density at the carbon from which the hydrogen migrates, and (b) this carbon center has a planar or nearly planar geometry.

Thermolysis of unsymmetrically substituted vinylcyclopropanes. The effect of substituents on the site-selectivity of homo-[1,5]-sigmatropic hydrogen migrations

Thermolysis of the unsymmetrical vinylcyclopropanes 18–24 reveals a notable substituent effect on the site-selectivity of homo-[1,5]-sigmatropic hydrogen shifts. Rearrangement of 18–20 (OMe substituent) produces only products 25–27, respectively (HA migration). In sharp contrast, thermolysis of 24 (Me3Si substituent) provides exclusively substance 34 (HX migration). Thermolysis of substrates bearing methyl (21, 22) or phenyl (23) groups provide, in each case, mixtures of the two possible products.

Formation of di-iron hexacarbonyl complexes of 3H-1,2-diazepines and the effects of complexation on ring inversion and the rate of sigmatropic hydrogen migration

A number of 3H-1,2-diazepines [(9)/(10)(a–f)] have been synthesised by the reactions of 6,7-dihydro-1-tosyl-1,2-diazepines with base. These diazepines are in dynamic equilibrium at room temperature via[1,5] sigmatropic hydrogen migrations but in some cases could be separated by h.p.l.c. at 0 °C. The reactions of 1H-2,3-benzodiazepines, 3H-1,2-benzodiazepines and the monocylic 3H-1,2-diazepines (9)/(10) with di-iron nonacarbonyl gave the dinuclear iron hexacarbonyl complexes (12), (14), and (15)/(16), respectively, in moderate yield. The complexes were found to undergo ring inversion more easily than their precursors, and activation energies were determined. The complexation of the azo group also stopped the easy [1,5] sigmatropic hydrogen shift observed for (9)/(10) and this is discussed in terms of changes in electronic effect and in the structural geometry of the diazepine ring.

Seven-membered ring annulation and spiro-annulation processes via preparation and thermal rearrangement of β-(2-vinylcyclopropyl) α,β-unsaturated ketones

Treatment of the β-iodo enones 4 and 26–28 with lithium (phenylthio)(2-vinylcyclopropyl)cuprate (21, mixture of epimers), followed by thermolysis (180 °C, 30–45 min) of the initially formed β-(2-vinylcyclopropyl) enones, provided excellent yields of the seven-membered ring annulation products 25 and 30–32, respectively. In similar fashion, the (E)-2-(iodomethylene)cycloalkanones 8 and 29 were transformed efficiently into the spiro-annulation products 34 and 35 respectively. When compound 36 was treated with bromoform – sodium hydroxide in the presence of a phase-transfer catalyst, the dibromocyclopropane 37 was produced. The latter substance served as the starting material for a sequence of reactions (hydrolysis with hydrochloric acid in methanol, 37 → 38; oxidation with pyridinium chlorochromate, 38 → 39; Wittig reaction with methylenetriphenylphosphorane, 39 → 40; reduction with zinc in acetic acid, 40 → 41) culminating in the stereoselective formation of cis-1-bromo-2,2-dimethyl-3-vinylcyclopropane (41). On the other hand, treatment of compound 37 with n-butyllithium (ether, −90 °C), followed by protonation of the presumed intermediate 43 and hydrolysis of the resultant product 44, provided the bromo alcohol 45 in 70% yield. The latter substance was converted into trans-1-bromo-2,2-dimethyl-3-vinylcyclopropane (47). When the cuprate reagents 42 and 48 (prepared from the bromocyclopropanes 41 and 47, respectively) were allowed to react with the iodo enones 4 and 26, the β-(2-vinylcyclopropyl) α,β-unsaturated ketones 49, 52, 54, and 56 were produced in high yields. The enone 49, upon thermolysis in refluxing n-hexane, underwent facile Cope rearrangement to produce the annulation product 50 quantitatively. In contrast, the homolog 54 was notably resistant to [3,3]-sigmatropic rearrangement and, upon thermolysis in o-xylene, o-dichlorobenzene, or collidine at elevated temperatures produced, in varying ratios, the Cope rearrangement product 55 and the isomerization product 56. Thermal rearrangement (o-dichlorobenzene, 220 °C, sealed tube) of trans-3-(2,2-dimethyl-3-vinylcyclopropyl)-2-cyclohexen-1-one (52) provided the annulation product 51 (59% yield). In contrast, the corresponding homolog 56, under very similar conditions, produced only a minor amount of the annulation product 55. In this case, the major product (trienone 57) was that resulting from a [1,5]-sigmatropic hydrogen migration (ratio of 55/57 ≈ 1:4).

Cuprates derived from endo-(n + 3)-bromobicyclo[n.1.0]alkanes and related compounds and their reaction with .beta.-iodo enones. Facile homo-[1,5]-sigmatropic hydrogen migrations involving endo-(n + 3)-(3-keto-1-cycloalkenyl)bicyclo[n.1.0]alkanes

Cuprates derived from endo-(n + 3)-bromobicyclo[n.1.0]alkanes and related compounds and their reaction with .beta.-iodo enones. Facile homo-[1,5]-sigmatropic hydrogen migrations involving endo-(n + 3)-(3-keto-1-cycloalkenyl)bicyclo[n.1.0]alkanes

Sigmatropic hydrogen migration and electrocyclization processes in compounds in the vitamin A series. Photochemistry of polyenes. 10.

Sigmatropic hydrogen migration and electrocyclization processes in compounds in the vitamin A series. Photochemistry of polyenes. 10.

Processus concurrents de photoisomerisation d'hexatrienes polymethyles: effet de longueur d'one

The ground-state conformer composition is shown to play a determining role in the orientation of the photochemical reactions of two hexatrienes. A pronounced wavelength effect is observed for Z-2,6-dimethyl-1,3,5-heptatriene; photocycloaddition leads to a bicyclo[3.1.0]hexene and [1,5] sigmatropic hydrogen migration occurs from an s- cis-s- trans conformation preferentially excited by longer wavelength light, whereas the Z-E interconversion is predominantly observed as a result of excitation of the s- trans-s- trans conformation by shorter wavelength light.