Variable Markovnikov orientation and "cis effect" in ene reactions of nitrosocarbonyl intermediates

Nitrosocarbonyl intermediates, generated at room temperature by the mild oxidation of nitrile oxides, undergo clean ene reactions with trisubstituted olefins. Allylic hydrogens on the more congested side of the alkene are exclusively abstracted (the "cis effect"), thus resembling singlet oxygen behavior. Nitrosocarbonyl benzene follows a Markovnikov orientation and abstracts preferentially the twix hydrogens over the lone ones. With the more sterically demanding nitrosocarbonyl mesitylene, the Markovnikov directing effect is relieved, and comparable twix and lone abstraction are observed.     

Thionin-sensitized intrazeolite photooxygenation of trisubstituted alkenes: substituent effects on the regioselectivity as probed through isotopic labeling

The regioselectivity for the intrazeolite photooxygenation of several trisubstituted alkenes with geminal dimethyl groups was examined. The length of the alkyl chain at the lone position was varied, and as end groups, the phenyl or the cyclohexyl functionalities were chosen. The general trend for all alkenes is a significant increase of the reactivity at the twin position compared to the photooxygenation in solution. For the cyclohexyl-substituted alkenes, it was found that the regioselectivity is nearly independent of the alkyl chain length. However, for the phenyl-substituted alkenes, the ene reactivity of the allylic methylene hydrogen atoms at the lone position and the twix/twin regioselectivity depend significantly on the distance of the phenyl group from the double bond. These trends are discussed in terms of cation-pi interactions and conformational effects. Intramolecular and intermolecular isotope effects in the intrazeolite photooxygenation of deuterium-labeled alkenes suggest that a perepoxide-type intermediate is formed in the rate-determining step. Type I photooxygenation that involves reaction of the radical cations of the alkenes with superoxide ion are unlikely.     

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     

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.     

An experimental and computational study on the reactivity and regioselectivity for the nitrosoarene ene reaction: comparison with triazolinedione and singlet oxygen

The regioselectivities and the reactivities (relative rates) for the ene reaction of the enophile 4-nitronitrosobenzene (ArNO) with an extensive set of regiochemically defined acyclic and cyclic olefins have been determined. These experimental data establish that the ArNO enophile attacks the olefinic substrate along the novel skew trajectory, with preferred hydrogen abstraction at the corner (twix regioselectivity). This is in contrast to the isoelectronic species singlet oxygen ((1)O(2)), which abstracts at the higher substituted side of the double-bond (cis effect), and triazolindione (TAD), which undergoes the ene reaction at the more crowded end (gem effect). Ab initio computations (B3LYP/6-31+g) for the ene reaction of the ArNO with 2-methyl-2-butene reveal that the steric effects between the aryl group of the enophile and the substituents of the olefin dictate the skew trajectory. These computations identify the aziridine N-oxide (AI) as a bona fide intermediate in this ene reaction, whose formation is usually rate-determining and, thus, irreversible along the skew trajectory (twix selectivity). The reversible generation of the AI becomes feasible when conformational constraints outweigh steric effects, as manifested by enhanced twin regioselectivity.     

Rate Dependence on Inductive and Resonance Effects for the Organocatalyzed Enantioselective Conjugate Addition of Alkenyl and Alkynyl Boronic Acids to β-Indolyl Enones and β-Pyrrolyl Enones

Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.     

Propellanes—XXXVII : Further testing of thesis regarding control by secondary orbital overlap during certain diels-alder reactions

We show again that compounds containing CO groups which are capable of secondary orbital interactions with the dienophile, 4-phenyl-1,2,4-triazoline-3,5-dione cause reaction to occur from above. However, in substrates which do not have capability for overlap with the dienophile nitrogen lone pairs and, on the contrary, exert steric hindrance to topside reaction, reaction with the first equivalent of dienophile occurs from below. When a second equivalent can react it reacts from above, again for relative steric reasons.     

Ene hydroperoxidation of isobutenylarenes within dye-exchanged zeolite Na-Y: control of site selectivity by cation-arene interactions

The site selectivity in the singlet oxygen ene reaction of several deuterium-labeled isobutenylarenes depends on the position and the electronic nature of the aryl substitutents. For example, 1-(4-trifluoromethylphenyl)-2-methylpropene gives 82% twin selectivity whereas the isomeric 1-(2-trifluoromethylphenyl)-2-methylpropene gives 68% twix selectivity. If photooxygenation of these CF(3)-substituted compounds is carried out in solution, the opposite selectivity trends are found. On the basis of DFT calculations, these results are rationalized in terms of oxygen-cation and cation-arene interactions.     

Mild and selective hydrozirconation of amides to aldehydes using Cp2Zr(H)Cl: scope and mechanistic insight

An investigation of the use of Cp2Zr(H)Cl (Schwartz's reagent) to reduce a variety of amides to the corresponding aldehydes under very mild reaction conditions and in high yields is reported. A range of tertiary amides, including Weinreb's amides, can be converted directly to the corresponding aldehydes with remarkable chemoselectivity. Primary and secondary amides proved to be viable substrates for reduction as well, although the yields were somewhat diminished as compared to the corresponding tertiary amides. Results from NMR experiments suggested the presence of a stable, 18-electron zirconacycle intermediate that presumably affords the aldehyde upon water or silica gel workup. A series of competition experiments revealed a preference of the reagent for substrates in which the lone pair of the nitrogen is electron releasing and thus more delocalized across the amide bond by resonance. This trend accounts for the observed excellent selectivity for tertiary amides versus esters. Experiments regarding the solvent dependence of the reaction suggested a kinetic profile similar to that postulated for the hydrozirconation of alkenes and alkynes. Addition of p-anisidine to the reaction intermediate resulted in the formation of the corresponding imine mimicking the addition of water that forms the aldehyde.     

Autocatalysis and surface catalysis in the reduction of imines by SmI2

The reduction of the three imines, N-benzylidene aniline (BAI), N-benzylidenemethylamine (BMI), and benzophenone imine (BPI), with SmI(2) gives the reduced as well as coupled products. The reactions were found to be autocatalytic due to the formation of the trivalent samarium in the course of the reaction. When preprepared SmI(3) was added to the reaction mixture, the reaction rate increased significantly. However, the kinetics were found to be of zero order in SmI(2). This type of behavior is typical of surface catalysis with saturation of the catalytic sites. Although no solids are visible to the naked eye, the existence of microcrystals was proven by light microscopy as well as by dynamic light scattering analysis. Although HRTEM shows the existence of quantum dots in the solid, we were unable to make a direct connection between the existence of the quantum dots and the catalytic phenomenon. In the uncatalyzed reaction, the order of reactivity is BPI > BMI > BAI. This order does not conform to the electron affinity order of the substrates but rather to the nitrogen lone pair accessibility for complexation. This conclusion was further supported by using HMPA as a diagnostic probe for the existence of an inner sphere electron transfer reaction.     

Substituent effects on the reactivity of benzo-1,2-dithiolan-3-one 1-oxides and their possible application to the synthesis of DNA-targeting drugs

The efficiency of polysulfane product generation has been investigated for n-propyl thiol reactions with ortho- and para-substituted benzo-1,2-dithiolan-3-one 1-oxides in acetonitrile-water (7:3) mixtures. The reaction is facilitated by reducing the electron density at the para position or by placing substituents bearing lone pair electrons ortho to the dithiolanone-oxide (S1) reaction center. Through-space and through-bond effects both contribute to the conversion of polysulfane products.     

H3PO→H2POH异构化反应的LMO研究

The localized molecular orbital (LMO) theory is used to study the reaction mechanism of the isomerization reaction: H_3PO→H_2POH. The energy transition state (TS) of the reaction is also obtained by Powell's mehtod using 6-31G basis set. The resluts show that the lone pair electrons of oxygen atom play an forortant role in this reaction.     

The thermal isomerization of 1-(α-aroyloxybenzylideneamino)-4,5-di-methyl-1,2,3-triazoles (isoimides) to the corresponding imides

The title isoimides rearrange upon heating to the corresponding imides through a [1,3] O⇀N aroyl transfer. The reaction is slightly accelarated by electron withdrawing substituents in the migrating moiety and retarded by electron donating as it is suggested by the positive (+0.5) Hammett ϱ value. The mechanism operating is either a rate determining nucleophilic attack by the nitrogen lone pair on the carbonyl carbon or a sigmatropic [π2s + σ2a] process which does not involve the lone pair of electrons on nitrogen and π or-bitals of the carbonyl group.     

Reactions of Charged Substrates. 7. The Methoxymethyl Carbenium Ion Problem. 2. A Semiempirical Study of the Kinetic and Thermodynamic Stabilities of Linear and Cyclic Oxo- and Thiocarbenium Ions Generated from Aldehyde Hydrates, Hemiacetals, Acetals, and Methyl Ribosides and Glucosides

Factors affecting the cleavage of the carbon-oxygen bond in linear and cyclic aldehyde hydrates, heimacetals, acetals, and methyl ribosides and glucosides have been investigated using semiempirical calculations (AM1 and PM3). (For some systems, low- and high-level ab initio energies are available for comparison with the semiempirical results. With one exception, the results obtained by the two methods show excellent agreement in relative energies and trends in reactivity.) The effects on reactivity and stability caused by substituting a sulfur for the alpha oxygen in the oxocarbenium ion were also studied. In general, systems that can have an antiperiplanar alignment of lone pairs on the leaving group and potential oxocarbenium ion oxygens undergo spontanteous cleavage. An examination of various conformers of the leaving group relative to the potential oxocarbenium oxygen shows, however, that lone pair repulsion and steric factors for MeOH as the leaving group are more important than the antiperiplanar effect for bond cleavage. All compounds in which the alpha-oxygen in the potential carbenium ion is replaced by sulfur undergo spontaneous cleavage regardless of the leaving group or structure of the compound. Energy profiles, DeltaH(), and DeltaH(R) values show that linear and cyclic thiocarbenium ions are much more stable than the corresponding oxocarbenium ions. Comparison of results for methyl ribosides and glucosides with results for corresponding pyridinium substrates suggests that both should hydrolyze through an A-1 mechanism. General-acid catalysis with hydronium as the acid was studied. With solution results, the computations suggest that substrates with either a good leaving group or stable oxocarbenium ion react with rate-limiting proton transfer from the acid to the leaving group but that substrates with both a good leaving group and stable carbenium ion react with concerted proton transfer and bond cleavage.     

Thermal [3,3]-rearrangement of 1,1-disubstituted allyl carboxylates: lone pair participation and the geminal bond participation

The diastereoselectivity of the [3,3]-rearrangement of 1,1-disubsstituted allyl carboxylates was studied. In this heteroatom-containing system, the transition state has a boat-like transition structure (TS) because of the participation of the lone pairs and the secondary orbital interaction. Although the TS for the [1,3]-rearrangement has a far higher barrier, it does not proceed in the usual antarafacial manner due to the cyclic orbital interaction among two lone pairs of the carboxylate and the allylic lumo. In conjunction with the geminal bond participation, delocalization to the σ-bond at the Z-position shows a bonding character in the transition state of the [3,3]-rearrangement. Therefore, we predicted that a more electron-withdrawing σ-bond prefers the Z-position in the product. We designed the 1,1-disubstituted substrates with trimethylsilyl and pentyl groups, and found that the trimethylsilyl group prefers the Z-position despite its steric bulkiness. We confirmed our prediction by experimentation. This Z-selectivity was improved when a trimethylgermyl group was used.     

孤对键弱化效应研究

在H_2O_2、N_2H_4、F_2分子中,O—O、N—N、F—F键的键长分别是0.148、0.148、0.144nm,虽比C_2H_6分子中的C—C键(0.154nm)短,但其σ键键能分别是146、160、155kJ/mol,却比C—C键能(365 kJ/mol)小约2.5倍,通常称这类原子的单键键能的反常现象为“孤对键弱化效应”。传统观点认为,半径很小的N、O、F等在化合时必须相当接近才能键合,孤对电子的排斥作用阻止了其相互接近,削弱了键能,降低了键的稳定性。显然,将这种削弱效应考虑为原子间效应是不合理的。本文用键参数图解法对“孤对键弱化效应”提出了合理的解释。     

Lower main-group element complexes with a soft scorpionate ligand: the structural influence of stereochemically active lone pairs

The syntheses and structures of complexes of the fifth period elements indium and antimony, and the sixth period element bismuth with the soft scorpionate ligand, hydrotris(methimazolyl)borate (Tm(Me)) are reported. A considerable variety of structural motifs were obtained by reaction of the main-group element halide and NaTm(Me). The indium(III) complexes took the form [In(kappa(3)-Tm(Me))(2)](+). This motif could not, however, be isolated for antimony(III), the dominant product being [Sb(kappa(3)-Tm(Me))(kappa(1)-Tm(Me))X] (X = Br, I). An iodo-bridged species [Sb(kappa(3)-Tm(Me))I(mu(2)-I)](2), analogous to a previously reported bismuth complex, was also isolated. Reaction of antimony(III) acetate with NaTm(Me) results in a remarkable species in which three different ligand binding modes are observed. In each antimony complex the influence of the nonbonded electron pair is observed in the structure. Bismuth halides form complexes analogous to those of antimony, with directional lone pairs, but in addition, reaction of Bi(NO(3))(3) with NaTm(Me) results in a complex with a regular S(6) coordination sphere and a nonstereochemically active lone pair. Comparisons are drawn with known Tm(Me) complexes of As, Sn, and Bi in which the stereochemical influence of the lone pairs is negligible and with Tm(Me) complexes of Te and Bi in which the lone pairs are stereochemically active. This study highlights the ability of Tm(Me) to coordinate in a variety of modes as dictated by the metal centre with no adverse effects on the stability of the complexes formed.     

Studies on lysergic acid diethylamide and related compounds—VI: Steric requirements of von braun reaction

It has been shown that in the ergot alkaloid series the von Braun reaction is hindered if there is a substituent which is 1,3-diaxial with respect to the nitrogen lone pair in the prefered conformation.     

Difficult substrates in the R-hydroxynitrile lyase catalyzed hydrocyanation reaction: application of the mass transfer limitation principle in a two-phase system

The application of a number of new and/or difficult substrates in the catalyzed hydrocyanation reaction by R-hydroxynitrile lyase from almonds is described. By using an aqueous–organic two-phase system and increasing the rate of the enzymatic reaction relative to the mass transfer rate, the enantiomeric purity was improved. By fine tuning the reaction parameters (temperature, pH, and the amount of enzyme) the hydrocyanation reaction was optimized for all substrates. The general principles described here can also be applied to optimize the reaction conditions for other substrates.     

Direct o-glycosyl trichloroacetimidate formation,nucleophilicity of the anomeric oxygen atom

Tetra-O-benzylglucose 1 and trichloroacetonitrile afford in a base catalyzed, fast, and reversible reaction the β-O-glycosyl imidate 3-β, which is transformed slowly into the α-isomer 3-α. Both results, the reactivity differences of 2α,β and the stability differences of 3-α/β are due to lone pair repulsions implicated in the anomeric effect.