吡咯喹啉醌模型化合物与氨亲核加成的理论探讨

为了揭示辅酶PQQ结构与反应性的关系,在B3LYP/D95(d, p)水平上对一系列PQQ模型化合物及其类似物与氨的亲核加成进行了理论计算.结果表明:对单羰基体系,羰基碳的亲电性对反应能垒有重要的影响;对双羰基体系,过渡态中邻位羰基氧与亲核试剂氨上的H形成的氢键对反应的活化能起着关键的作用;稠合芳香环本身对反应的能垒影响不大,但当稠合杂环的1-位为可提供氢键受体的N原子时,由于N1与氨上H原子间可形成氢键而进一步降低反应的活化能.发现过渡态中被进攻羰基与氨上N原子之间形成的夹角(OCN)与活化能有良好的线性关系.     

Theoretical Study of the Regioselectivity of the Interaction of 3-Methyl-4-pyrimidone and 1-Methyl-2-pyrimidone with Lewis Acids

A density functional theory (DFT) study is performed to determine the stability of the complexes formed between either the N or O site of 3-methyl-4-pyrimidone and 1-methyl-2-pyrimidone molecules and different ligands. The studied ligands are boron and alkali Lewis acids, namely, B(CH(3))(3), HB(CH(3))(2), H(2)B(CH(3)), BH(3), H(2)BF, HBF(2), BF(3), Li(+), Na(+), and K(+). The acids are divided into two groups according to their hardness. The reactivity predictions, according to the molecular electrostatic potential (MEP) map and the natural bond orbital (NBO) analysis, are in agreement with the calculated relative stabilities. Our findings reveal a strong regioselectivity with borane and its derivatives preferring the nitrogen site in both pyrimidone isomers, while a preference for oxygen is observed for the alkali acids in the 3-methyl-4-pyrimidone molecule. The complexation of 1-methyl-2-pyrimidone with these hard alkali acids does not show any discrimination between the two sites due to the presence of a continuous delocalized density region between the nitrogen and the oxygen atoms. The preference of boron Lewis acids toward the N site is due to the stronger B-N bond as compared to the B-O bond. The influence of fluorine or methyl substitution on the boron atom is discussed through natural orbital analysis (NBO) concentrating on the overlap of the boron empty p-orbital with the F lone pairs and methyl hyperconjugation, respectively. The electrophilicity of the boron acids gives a good overall picture of the interaction capabilities with the Lewis base.     

Palladation of diimidazolium salts at the C4 position: access to remarkably electron-rich palladium(II) centers

Palladation of C2-protected diimidazolium salts with Pd(OAc)2 afforded complexes comprising C4-bound N-heterocyclic dicarbene ligands. The reactivity of these complexes towards Lewis acids (AgBF4, AgOAc) and Br?nsted acids (H2SO4, H3PO4, HOAc) revealed that abnormal C4 bonding of the carbenes markedly increases the nucleophilicity of the coordinated palladium center as compared to C2 bonding. Despite its formal +2 charge, the palladium center in these complexes is best described as a Lewis base. The abnormal carbene bonding mode induces new reaction patterns such as the formation of a Pd-Ag adduct. Based on metallation studies including the palladation of a dissymmetric diimidazolium salt, a rationale for the selective activation of the C4-H bond in the diimidazolium precursor salts is proposed.     

Influence of Solvent on the Reaction of Diphenyl Carbonyl Oxide with Benzaldehyde

Influence of the solvent on the relative rate constant for the reaction of benzophenone oxide with benzaldehyde has been studied. The solvent influence can be quantitatively described by the semi-empirical Koppel-Palm equation. It is shown that non-specific solvation due to electrostatic interactions lowers, while polarizability enhances the reactivity of diphenyl carbonyl oxide. The specific solvation affects the reaction mainly through the parameter of electrophilicity by decreasing the carbonyl oxide reactivity.     

Synthesis of Boron-containing Complexes of 1-(2-hydroxyphenyl)-3-phenyl-2-propen-1-one

Condensation of o-hydroxyacetophenone with benzaldehyde in alcohol in the presence of a triple excess of a sodium hydroxide solution leads to 2'-hydroxychalcone sodium salt. The latter was heated with boron trifluoride etherate in toluene to a 2'-hydroxychalcone boron fluoride complex in which the boron atom is coordinated to the carbonyl oxygen atom. The same complex was obtained by boiling of the o-hydroxyacetophenone boron fluoride complex with benzaldehyde in acetic anhydride.     

A Phosphinine-Derived 1-Phospha-7-Bora-Norbornadiene: Frustrated Lewis Pair Type Activation of Triple Bonds

Salt metathesis of 1-methyl-2,4,6-triphenylphosphacyclohexadienyl lithium and chlorobis(pentafluorophenyl)borane affords a 1-phospha-7-bora-norbornadiene derivative 2 . The C≡N triple bonds of nitriles insert into the P−B bond of 2 with concomitant C−B bond cleavage, whereas the C≡C bonds of phenylacetylenes react with 2 to form λ⁴-phosphabarrelenes. Even though 2 must formally be regarded as a classical Lewis adduct, the C≡N and C≡C activation processes observed (and the mild conditions under which they occur) are reminiscent of the reactivity of frustrated Lewis pairs. Indeed, NMR and computational studies give insight into the mechanism of the reactions and reveal the labile nature of the phosphorus–boron bond in 2 , which is also suggested by detailed NMR spectroscopic studies on this compound. Nitrile insertion is thus preceded by ring opening of the bicycle of 2 through P−B bond splitting with a low energy barrier. By contrast, the reaction with alkynes involves formation of a reactive zwitterionic methylphosphininium borate intermediate, which readily undergoes alkyne 1,4-addition.     

Scales of Nucleophilicity and Electrophilicity: A System for Ordering Polar Organic and Organometallic Reactions

Contrary to widely held opinion, for many reactions in organic and organometallic chemistry it is possible to define nucleophilicity and electrophilicity parameters that are independent of the reaction partners. This phenomenon, discovered by Ritchie during the early 1970s for reactions of highly stabilized carbenium and diazonium ions with n-nucleophiles, also occurs with reactions of carbenium ions with aliphatic and aromatic π-electron systems and in hydride transfer reactions. With the aid of the scales of nucleophilicity and electrophilicity set out here, which extend over eighteen orders of magnitude, forecasts can be made about the feasibility and rate of a given CC bond formation, ionic reduction, or diazo coupling. Linkage with the reactivity scales of Ritchie and Sweigart/Kane-Maguire enables a unified treatment of a large number of polar reactions.     

Hard-soft acid-base interactions of silylenes and germylenes

A detailed investigation of the electrophilic and nucleophilic character of singlet silylenes and germylenes, divalent compounds of silicon and germanium, respectively, substituted by first- and second-row elements is presented. In a first part, the Lewis acid properties of these compounds were studied through their complexation reaction with the Lewis bases NH3, PH3, and AsH3. The results indicate that this complexation is most favorable with the hardest base NH3, classifying these compounds as hard Lewis acids. This is confirmed by the linear correlation between the interaction energies and the value of the electrostatic potential, used as an approximation to the local hardness, near the empty p orbital of these compounds, indicating a charge-controlled interaction in the complex. Also the electrophilicity index, proposed by Parr et al., computed both at the global and the local level, correlates linearly with the complexation energies of the compounds with NH3. The Lewis base character of these silylenes has been investigated, through their interaction with the acids BH3 and AlH3. Also in this case, the electrostatic potential can be used to probe the reactivity of the compounds. It will finally be demonstrated that an increasing stability of the silylenes and germylenes is accompanied by an increase in their nucleophilicity and a decrease of the electrophilicity.     

On the mechanism of irreversible carbon dioxide binding with a frustrated lewis pair: solvent-assisted frustration and transition-state entropic encouragement

The mechanism of irreversible carbon dioxide binding with a Lewis pair Mes(3)P:AlCl(3) (Mes=2,4,6-C(6)H(2)Me(3)) is computationally investigated to reveal that the steric congestion is not the driving force for the activation of CO(2). Instead, we find that the specific solute-solvent interaction between the Lewis acid and a bromobenzene molecule lowers the effective binding energy of the Lewis pair. This solvation effect affects the reaction in a similar manner to the steric encumbering of conventional frustrated Lewis pairs. Additionally, the transition state toward the CO(2) binding becomes extraordinarily flexible upon solvation. This flexibility encourages the adduct formation entropically and thus lowers the free-energy barrier of the reaction. We conclude that this combination of energy-barrier lowering through solvent-assisted frustration and the entropic encouragement generates a feasible activation route for CO(2) under mild conditions.     

Investigation into the Regiochemistry of 1,3‐Dipolar Cycloaddition of C,N‐Diphenyl Nitrone with Some Vinyl Sulfoximines as Dipolarophile: Theoretical Studies

The regiochemistry of 1,3‐dipolar cycloaddition reactions of C,N‐diphenyl nitrone with some vinyl sulfox‐ imines as dipolarophile was investigated using density functional theory (DFT)‐based reactivity indexes and activation energy calculations at B3LYP/6‐31G(d) level of theory. Analysis of the geometries and bond orders (BOs) at the TS structures associated with the different reaction pathways shows that these 1,3‐dipolar cycloaddition reactions occur via an asynchronous concerted mechanism. Analysis of the local electrophilicity and nucleophilicity indexes permits an interpretation about the regioselectivity of these 1,3‐dipolar cycloaddition reactions. The theoretical results obtained in the work clearly predict the regiochemistry of the isolated cycloadducts and agree to experimental outcomes.     

Mechanism of Ketone Allylation with Allylboronates as Catalyzed by Zinc Compounds: A DFT Study

The mechanism of the allylation reaction between 4‐chloroacetophenone and pinacol allylboronates catalyzed by ZnEt₂ with alcohols was investigated using density functional theory (DFT) at the M05‐2X/6‐311++G(d,p) level. The calculations reveal that the reaction prefers to proceed through a double γ‐addition stepwise reaction mechanism rather than a Lewis acid‐catalyzed concerted one. The intermediate with a four‐coordinated boron center, which is formed through proton transfer from EtOH to the ethyl group of ZnEt₂ mediated by the boron center, is the active species and an entrance for the catalytic cycle. The latter is composed of three elementary steps: 1) boron to zinc transmetalation leading to the formation of allylzincate species, 2) electrophilic addition of ketone to allylzincate species, and 3) generation of the final product with recovery of the catalyst. The boron to zinc transmetalation step has the largest energy barrier of 61.0 kJ mol^?1 and is predicted to be the rate‐determining step. The calculations indicate that the additive EtOH plays important roles both in lowering the activation free energy for the formation of the four‐coordinated boron active intermediate and in transforming the low catalytic activity ZnEt₂ into high activity zinc alkoxide species. The alcohols with a less sterically encumbering R group might be the effective additives. The substituted groups on the allylboronates might primarily affect the boron to zinc transmetalation, and the allylboronates with substituents on the C_γ atom is poor in reactivity. The comparison of the catalytic effect between the zinc compounds investigated suggest that Zn(OEt)₂, Zn(OH)₂, and ZnF₂ exhibit higher catalytic efficiency for the boron to zinc transmetalation due to the activation of the B? C_α bond through orbital interactions between the p orbitals of the EtO, OH, F groups and the empty p orbital of the boron center.     

Direct conversion of carbonyl compounds into organic halides: indium(III) hydroxide-catalyzed deoxygenative halogenation using chlorodimethylsilane

The reaction of carbonyls and chlorodimethylsilane was effectively catalyzed by indium(III) hydroxide and afforded the corresponding deoxygenative chlorination products, in which the carbonyl carbon accepted two nucleophiles (H and Cl) with releasing oxygen. Only In(OH)3 catalyzed the reaction, and typical Lewis acids such as TiCl4, AlCl3, and BF3.OEt2 showed no catalytic activity. The reaction mechanism of this deoxygenative chlorination includes initial hydrosilylation followed by chlorination. Other nucleophiles such as allyl or iodine were available for this methodology. The moderate Lewis acidity of indium catalyst enabled chemoselective reaction, and therefore ester, nitro, cyano, or halogen groups were not affected during the reaction course.     

Impact of Lewis acids on Diels-Alder reaction reactivity: a conceptual density functional theory study

Density functional theory (DFT) and conceptual/chemical DFT studies are carried out in this work for the normal electron demand Diels-Alder reaction between isoprene and acrolein to compare chemical reactivity and regioselectivity of the reactants in the absence and presence of Lewis acid (LA) catalysts. A cyclic coplanar structure of acrolein-LA complex has been observed and the natural bond orbital analysis has been employed to interpret the interaction between acrolein and LAs. Reactivity indices from frontier molecular orbital energies are proved to be adequate and efficient to evaluate the catalytic property of LAs. Linear relationships have been discovered among the bond order, bond length, catalytic activation, and chemical reactivity for the systems concerned. The validity and applicability of maximum hardness principle, minimum polarizability principle, and minimum electrophilicity principle are examined and discussed in the prediction of the major regioselective isomer and the preferred reaction pathway for the reactions in the present study.     

Mechanistic Investigation of Chiral Phosphoric Acid Catalyzed Asymmetric Baeyer–Villiger Reaction of 3‐Substituted Cyclobutanones with H2O2 as the Oxidant

The mechanism of the chiral phosphoric acid catalyzed Baeyer–Villiger (B–V) reaction of cyclobutanones with hydrogen peroxide was investigated by using a combination of experimental and theoretical methods. Of the two pathways that have been proposed for the present reaction, the pathway involving a peroxyphosphate intermediate is not viable. The reaction progress kinetic analysis indicates that the reaction is partially inhibited by the γ‐lactone product. Initial rate measurements suggest that the reaction follows Michaelis–Menten‐type kinetics consistent with a bifunctional mechanism in which the catalyst is actively involved in both carbonyl addition and the subsequent rearrangement steps through hydrogen‐bonding interactions with the reactants or the intermediate. High‐level quantum chemical calculations strongly support a two‐step concerted mechanism in which the phosphoric acid activates the reactants or the intermediate in a synergistic manner through partial proton transfer. The catalyst simultaneously acts as a general acid, by increasing the electrophilicity of the carbonyl carbon, increases the nucleophilicity of hydrogen peroxide as a Lewis base in the addition step, and facilitates the dissociation of the OH group from the Criegee intermediate in the rearrangement step. The overall reaction is highly exothermic, and the rearrangement of the Criegee intermediate is the rate‐determining step. The observed reactivity of this catalytic B–V reaction also results, in part, from the ring strain in cyclobutanones. The sense of chiral induction is rationalized by the analysis of the relative energies of the competing diastereomeric transition states, in which the steric repulsion between the 3‐substituent of the cyclobutanone and the 3‐ and 3′‐substituents of the catalyst, as well as the entropy and solvent effects, are found to be critically important.     

Stereoselective Synthesis of Novel Diels–Alder Adducts of p-Substituted Methyl Thiocinnamates and Cyclopentadiene

This article describes the Diels–Alder reaction between methyl thiocinnamates, substituted at the para position by electron-donating and electron-withdrawing groups, with cyclopentadiene in the presence of catechol boron bromide (CBB) as a Lewis acid catalyst. The adduct configuration was confirmed by ¹H NMR coupling constants and single-crystal x-ray diffraction. Total endo stereoselectivity was observed in all reactions and was attributed to the effective secondary interaction between the boron atom and the incipient double bond in the norbonene resulting from the planar geometry of the catalyst. ¹³C NMR chemical shifts of the coordinated dienophile carbonyl carbons with CBB compared to those of the non coordinated thiocinammates suggest a strong complexation with the catalyst.     

N- versus P-coordination in bis(amino)cyclodiphosph(III)azane complexes of aluminum

The reaction of the bis(amino)cyclodiphosph(III)azane, cis-{(tBuNH)(2)(PNtBu)(2)}, with AlMe(3), AlClMe(2), AlCl(2)Me, and AlCl(3) is reported. The less Lewis acidic compound AlMe(3) forms the adduct cis-[(tBuNH)(2)(PNtBu){P.(AlMe(3))NtBu}] (1), in which the aluminum atom is exclusively coordinated to one phosphorus atom. At elevated temperatures AlMe(3) undergoes migratory exchange between the two phosphorus atoms, but no methane elimination is observed. By using the more Lewis acidic compound AlClMe(2) the P-coordinated compound cis-[(tBuNH)(2)(PNtBu){P(AlClMe(2))NtBu}] (2) can be obtained at low temperatures. Compound 2 rearranges irreversibly to a product in which the AlClMe(2) group is coordinated by one exo-cyclic nitrogen atom. A concomitant 1,2-H shift from this nitrogen atom onto the phosphorus atom is observed. The N-coordinated rearrangement product slowly decomposes via a P-N bond cleavage in solution. Reaction of the even more Lewis acidic compounds AlCl(2)Me and AlCl(3) finally led to stable adducts, cis-[(tBuNH)(PNtBu)(tBuNAlCl(2)Me){P(H)NtBu}] (3), and cis-[(tBuNH)(PNtBu)(tBuNAlCl(3)){P(H)NtBu}] (4), in which the aluminum atoms are N-coordinated by a tBuN=PH unit.     

Boron–Ligand Cooperation: The Concept and Applications

The term boron–ligand cooperation was introduced to describe a specific mode of action by which certain metal-free systems activate chemical bonds. The main characteristic of this mode of action is that one covalently bound substituent at the boron is actively involved in the bond activation process and changes to a datively bound ligand in the course of the bond activation. Within this review, how the term boron–ligand cooperation evolved is reflected on and examples of bond activation by boron–ligand cooperation are discussed. It is furthermore shown that systems that operate via boron–ligand cooperation can complement the reactivity of classic intramolecular frustrated Lewis pairs and applications of this new concept for metal-free catalysis are summarized.     

Synthesis and Catalytic Activity of Atrane-type Hard and Soft Lewis Superacids with a Silyl,Germyl, or Stannyl Cationic Center

The synthesis and isolation of atrane-type molecules 1 E⁺ (E=Si, Ge, or Sn) having a cationic group 14 elemental center are reported. The cations 1 E⁺ act as hard and soft Lewis superacids, which readily interact with various hard and soft Lewis basic substrates. The rigid atrane framework stabilizes the localized positive charge on the elemental center and assists the formation of the well-defined highly coordinated states of 1 E⁺. The cations were applied to the hydrodefluorination, Friedel-Crafts reaction, alkyne cyclization, and carbonyl reduction as Lewis acid catalysts. Most notably, [ 1 Si][ClO₄] exhibits unique chemoselectivity that depends on a solvent in the competitive reaction of silyl enol ether with a mixture of benzaldehyde dimethyl acetal and benzaldehyde. Our findings indicate the potential of hard and soft Lewis superacids in organic synthesis.     

Theoretical study of the asymmetric conjugate alkenylation of enones catalyzed by binaphthols

To rationalize the experimental results observed in the asymmetric conjugate addition of alkenylboronates to enones catalyzed by binaphthols and shed light into the factors controlling the rate, the selectivity, and the substituent effects of this process, a theoretical DFT study has been performed. The calculations suggest the catalytic cycle is finely balanced. Reversible exchange of methoxy ligands gives rise to the binaphthol-derived alkenylboronate, which is highly Lewis acidic and strongly coordinates to the enone carbonyl in a reversible fashion, lowering the energy barrier for the subsequent conjugate addition step. The key asymmetric step goes through a sofalike transition structure in which the boron atom is strongly bound to the carbonyl oxygen and lies in the plane of the enone moiety. A steric clash between one of the iodine atoms of the ligand and one face of the enone seems to be responsible for the facial discrimination. The alternative reaction channel in which only one methoxy ligand of the alkenylboronate is exchanged was investigated too and was computed to be disfavored. The [4 + 2] and the [4 + 3] pathways for the competitive hetero-Diels-Alder reaction were also found to be disfavored relative to the conjugate alkenylboration. In addition, the effects of substitution on the enone and the alkenylboronate have been evaluated. Calculations correctly reproduced the experimental reactivity trends and enantiomeric ratios.