Effect of Ring Size and Migratory Groups on [1,n] Suprafacial Shift Reactions. Confirmation of Aromatic and Antiaromatic Transition-State Character by Ring-Current Analysis.

Suprafacial sigmatropic shift reactions of 5-substituted cyclopentadienes, 3-substituted cyclopropenes, and 7-substituted cycloheptatrienes have been studied computationally at the MP2/6-31+G* level for structures and energetics and with the ipsocentric method at the CHF/6-31G** level to calculate current-density maps. The hydrogen shifts in cyclopentadienes have a diatropic ring current indicating aromatic, cyclopentadienide anion character. This result stands in contrast to the fluorine shift in 5-fluorocyclopentadiene which requires much more energy and has a paratropic ring current in the TS pointing to antiaromatic, cyclopentadienyl cation character. [1,3] hydrogen shifts in cyclopropenes are very difficult, passing through transition states that have an extended C-C bond. For 3-fluorocyclopropene, the [1,3] fluorine shift is much easier than the hydrogen shift. For 7-fluorocycloheptatriene, the [1,7] hydrogen shift is predicted but requires very high energy and has a paratropic ring current and antiaromatic character. The [1,7] suprafacial fluorine shift is relatively easy, having a TS with cycloheptatrienyl cation character. Patterns of currents, and the reversal for H and F migration, are rationalized by orbital analysis based on the ipsocentric method. Calculated charges and structural features for reactants and transition states support these conclusions.

Are copper(I) carbenes capable intermediates for cyclopropanations? The case for ylide intermediates.

A novel approach is used to synthesize a stable, ligated copper(I) carbene in the gas phase that is capable of typical metal carbenoid chemistry. However, it is shown that copper(I) carbenes generally undergo rapid unimolecular rearrangements including insertions into copper-ligand bonds and Wolff rearrangements. The results indicate that most copper(I) carbenes are inherently unstable and would not be viable intermediates in condensed-phase applications; an alternative intermediate that is less prone to rearrangements is required. Computational data suggest that ylides formed by the complexation of the carbene with solvent or other weak nucleophiles are viable intermediates in the reactions of copper(I) carbenes.

Effect of allylic groups on S(N)2 reactivity.

The activating effects of the benzyl and allyl groups on S(N)2 reactivity are well-known. 6-Chloromethyl-6-methylfulvene, also a primary, allylic halide, reacts 30 times faster with KI/acetone than does benzyl chloride at room temperature. The latter result, as well as new experimental observations, suggests that the fulvenyl group is a particularly activating allylic group in S(N)2 reactions. Computational work on identity S(N)2 reactions, e.g., chloride(-) displacing chloride(-) and ammonia displacing ammonia, shows that negatively charged S(N)2 transition states (tss) are activated by allylic groups according to the Galabov-Allen-Wu electrostatic model but with the fulvenyl group especially effective at helping to delocalize negative charge due to some cyclopentadienide character in the transition state (ts). In contrast, the triafulvenyl group is deactivating. However, the positively charged S(N)2 transition states of the ammonia reactions are dramatically stabilized by the triafulvenyl group, which directly conjugates with a reaction center having S(N)1 character in the ts. Experiments and calculations on the acidities of a variety of allylic alcohols and carboxylic acids support the special nature of the fulvenyl group in stabilizing nearby negative charge and highlight the ability of fulvene species to dramatically alter the energetics of processes even in the absence of direct conjugation.

Reactivity in the nucleophilic aromatic substitution reactions of pyridinium ions.

The "element effect" in nucleophilic aromatic substitution reactions (SNAr) is characterized by the leaving group order, L = F > NO2 > Cl ≈ Br > I, in activated aryl substrates. A different leaving group order is observed in the substitution reactions of ring-substituted N-methylpyridinium compounds with piperidine in methanol: 2-CN ≥ 4-CN > 2-F ∼ 2-Cl ∼ 2-Br ∼ 2-I. The reactions are second-order in [piperidine], the mechanism involving rate determining hydrogen-bond formation between piperidine and the substrate-piperidine addition intermediate followed by deprotonation of this intermediate. Computational results indicate that deprotonation of the H-bonded complex is probably barrier free, and is accompanied by simultaneous loss of the leaving group (E2) for L = Cl, Br, and I, but with subsequent, rapid loss of the leaving group (E1cB-like) for the poorer leaving groups, CN and F. The approximately 50-fold greater reactivity of the 2- and 4-cyano substrates is attributed to the influence of the electron withdrawing cyano group in the deprotonation step. The results provide another example of ß-elimination reactions poised near the E2-E1cB mechanistic borderline.

Stabilities of Uracil and Pyridone-Based Carbanions: A Systematic Study in the Gas Phase and Solution and Implications for the Mechanism of Orotidine-5'-Monophosphate Decarboxylase.

The stabilities of the C6-centered carbanions derived from 1,3-dimethyluracil, N-methyl-2-pyridone, and N-methyl-4-pyridone were systematically investigated in the gas phase and in DMSO and water solutions. The stabilities of the carbanions in the gas phase and DMSO were directly measured through their reactions with carbon acids with known proton affinity or pKa values. The stabilities of the carbanions in DMSO were also probed through their kinetic isotope effects of protonation over deuteriation using acids with different acidity. The stabilities of the carbanions in water were determined through the rates of hydrogen-deuterium exchange reactions of the corresponding conjugate acids. The carbanions derived from the two pyridones were found to have the same stability, whereas the carbanion derived from 1,3-dimethyluracil was more stable. The order of the stability of the carbanions showed no correlation with the decarboxylation rates of their corresponding carboxylic acids. The implications of the results for the mechanism of orotidine-5'-monophosphate decarboxylase (ODCase) are discussed.

Base-catalyzed dehydration of 3-substituted benzene cis-1,2-dihydrodiols: stabilization of a cyclohexadienide anion intermediate by negative aromatic hyperconjugation.

Evidence that a 1,2-dihydroxycyclohexadienide anion is stabilized by aromatic "negative hyperconjugation" is described. It complements an earlier inference of "positive" hyperconjugative aromaticity for the cyclohexadienyl cation. The anion is a reactive intermediate in the dehydration of benzene cis-1,2-dihydrodiol to phenol. Rate constants for 3-substituted benzene cis-dihydrodiols are correlated by σ(-) values with ρ = 3.2. Solvent isotope effects for the reactions are k(H(2)O)/k(D(2)O) = 1.2-1.8. These measurements are consistent with reaction via a carbanion intermediate or a concerted reaction with a "carbanion-like" transition state. These and other experimental results confirm that the reaction proceeds by a stepwise mechanism, with a change in rate-determining step from proton transfer to the loss of hydroxide ion from the intermediate. Hydrogen isotope exchange accompanying dehydration of the parent benzene cis-1,2-dihydrodiol was not found, and thus, the proton transfer step is subject to internal return. A rate constant of ~10(11) s(-1), corresponding to rotational relaxation of the aqueous solvent, is assigned to loss of hydroxide ion from the intermediate. The rate constant for internal return therefore falls in the range 10(11)-10(12) s(-1). From these limiting values and the measured rate constant for hydroxide-catalyzed dehydration, a pK(a) of 30.8 ± 0.5 was determined for formation of the anion. Although loss of hydroxide ion is hugely exothermic, a concerted reaction is not enforced by the instability of the intermediate. Stabilization by negative hyperconjugation is proposed for 1,2-dihydroxycyclohexadienide and similar anions, and this proposal is supported by additional experimental evidence and by computational results, including evidence for a diatropic ("aromatic") ring current in 3,3-difluorocyclohexadienyl anion.

The element effect revisited: factors determining leaving group ability in activated nucleophilic aromatic substitution reactions.

The "element effect" in nucleophilic aromatic substitution reactions (S(N)Ar) is characterized by the leaving group order, F > NO(2) > Cl ≈ Br > I, in activated aryl halides. Multiple causes for this result have been proposed. Experimental evidence shows that the element effect order in the reaction of piperidine with 2,4-dinitrophenyl halides in methanol is governed by the differences in enthalpies of activation. Computational studies of the reaction of piperidine and dimethylamine with the same aryl halides using the polarizable continuum model (PCM) for solvation indicate that polar, polarizability, solvation, and negative hyperconjugative effects are all of some importance in producing the element effect in methanol. In addition, a reversal of polarity of the C-X bond from reactant to transition state in the case of ArCl and ArBr compared to ArF also contributes to their differences in reactivity. The polarity reversal and hyperconjugative influences have received little or no attention in the past. Nor has differential solvation of the different transition states been strongly emphasized. An anionic nucleophile, thiolate, gives very early transition states and negative activation enthalpies with activated aryl halides. The element effect is not established for these reactions. We suggest that the leaving group order in the gas phase will be dependent on the exact combination of nucleophile, leaving group, and substrate framework. The geometry of the S(N)Ar transition state permits useful, qualitative conceptual distinctions to be made between this reaction and other modes of nucleophilic attack.

Stabilities of carbenes: independent measures for singlets and triplets.

Thermodynamic stabilities of 92 carbenes, singlets and triplets, have been evaluated on the basis of hydrogenation enthalpies calculated at the G3MP2 level. The carbenes include alkyl-, aryl-, and heteroatom-substituted structures as well as cyclic 1,3-diheteroatom carbenes. Over a wide energy range, a good correlation is seen between the singlet-triplet gaps and the hydrogenation enthalpies of the singlets, but there are some clear outliers, which represent cases where the triplet has unusual stability or instability. By use of hydrogenation enthalpies, separate carbene stabilization enthalpy scales (CSEs) have been developed for singlets and triplets, and these highlight structural features that affect the stability of each. The treatment also allows estimates of aromaticity in cyclic carbenes. In this way, imidazol-2-ylidene is estimated to have an aromatic stabilization energy of about 20 kcal/mol.

Hyperaromatic stabilization of arenium ions: cyclohexa- and cycloheptadienyl cations-experimental and calculated stabilities and ring currents.

Measurements of pK(R) show that the cycloheptadienyl cation is less stable than the cyclohexadienyl (benzenium) cation by 18 kcal mol(-1). This difference is ascribed here to "hyperaromaticity" of the latter. For the cycloheptadienyl cation a value of K(R) = [ROH][H(+)]/[R(+)] is assigned by combining a rate constant for reaction of the cation with water based on the azide clock with a rate constant for the acid-catalyzed formation of the cation accompanying equilibration of cycloheptadienol with its trifluoroethyl ether in TFE-water mixtures. Comparison of pK(R) = -16.1 with pK(R) = -2.6 for the cyclohexadienyl cation yields the difference in stabilities of the two ions. Interpretation of this difference in terms of hyperconjugative aromaticity is supported by the effect of benzannelation in reducing pK(R) for the benzenium ion: from -2.6 down to -3.5 for the 1H-naphthalenium and -6.0 for the 9H-anthracenium ions, respectively. MP2/6-311+G** and G3MP2 calculations of hydride ion affinities of benzenium ions show an order of stabilities for substituents at the methylene group consistent with their hyperconjugative abilities, i.e., (H(3)Si)(2) > cyclopropyl > H(2) > Me(2)> (HO)(2) > F(2). Calculations of ring currents show a similar ordering. No conventional ring current is seen for the cycloheptadienyl cation, whereas currents in the F(2)-substituted benzenium ion are consistent with antiaromaticity. Arenium ions where the methylene group is substituted with a single OH group show characteristic energy differences between conformations, with C-H or C-OH bonds respectively occupying or constrained to axial positions favorable to hyperconjugation. The differences were found to be 8.8, 6.3, 2.4, and 0.4 kcal mol(-1) for benzenium, naphthalenium, phenanthrenium, and cyclohexenyl cations, respectively.

Hyperaromatic stabilization of arenium ions.

Benzene-cis- and trans-1,2-dihydrodiols undergo acid-catalyzed dehydration at remarkably different rates: k(cis)/k(trans) = 4500. This is explained by formation of a ß-hydroxycarbocation intermediate in different initial conformations, one of which is stabilized by hyperconjugation amplified by an aromatic no-bond resonance structure (HOC(6)H(6)(+) ↔ HOC(6)H(5) H(+)). MP2 calculations and an unfavorable effect of benzoannelation on benzenium ion stability, implied by pK(R) measurements of -2.3, -8.0, and -11.9 for benzenium, 1-naphthalenium, and 9-phenanthrenium ions, respectively, support the explanation.

The protonation of allene and some heteroallenes, a computational study.

Protonation of allene and seven heteroallenes, X = Y = Z, at the terminal and central positions has been studied computationally at the MP2/6-311+G**, B3LYP/6-31+G**, and G3 levels. In all but one case protonation at a terminal position is preferred thermodynamically. The exception is allene, where protonation at C2 giving allyl cation prevails by about 10 kcal/mol over end-protonation, which gives the 2-propenyl cation. In the heteroallenes, protonation at a terminal carbon is strongly favored, activated by electron donation from the other terminal atom. Transition states for identity proton-transfer reactions were found for 10 of the "end-to-end" proton transfers. When the transfer termini are heteroatoms these processes are barrier free. We found no first-order saddle point structures for "center-to-center" proton transfers. An estimate of DeltaH++ for an identity center-to-center proton transfer could be made only for the reaction between the allyl cation and allene; it is approximately 22 kcal/mol higher than DeltaH++ for the end-to-end proton transfer between the 2-propenyl cation and allene. First-order saddle points for the proton transfer from H3S+ to both C1 and C2 of allene were found. The difference in activation enthalpies is 9.9 kcal/mol favoring protonation at C1 in spite of the thermodynamic disadvantage. We infer that protonation of X = Y = Z at central atoms passes through transition states much like primary carbenium (nitrenium, oxenium) cations, poorly conjugated with the attached vinylic or heterovinylic group. Several other processes following upon center protonation were studied and are discussed in the text, special attention being given to comparison of open and cyclic isomers.

Primary semiclassical kinetic hydrogen isotope effects in identity carbon-to-carbon proton- and hydride-transfer reactions, an ab initio and DFT computational study.

Enthalpies of activation, transition state (ts) geometries, and primary semiclassical (without tunneling) kinetic isotope effects (KIEs) have been calculated for eleven bimolecular identity proton-transfer reactions, four intramolecular proton transfers, four nonidentity proton-transfer reactions, eleven identity hydride transfers, and two 1,2-intramolecular hydride shifts at the HF/6-311+G, MP2/6-311+G, and B3LYP/6-311++G levels. We find the KIEs to be systematically smaller for hydride transfers than for proton transfers. This outcome is not the result of "bent" transition states, although extreme bending can lower the KIE. Rather, it is a consequence of generally greater total bonding in a hydride-transfer ts than in a proton-transfer ts, most prominently manifested as a reduced contribution from the zero-point vibrational energy difference between reactant and transition states (the DeltaZPVE factor) for hydride transfers relative to proton transfers. This and other differences between proton and hydride transfers are rationalized by modeling the central .C...H...C unit of a proton-transfer ts as a 4-electron, 3-center (4-e 3-c) system and the same unit of a hydride-transfer ts as a 2-e 3-c system. Inclusion of tunneling is most likely to magnify the observed differences between proton-transfer and hydride-transfer KIEs, leaving our qualitative conclusions unchanged.

Identity hydride-ion transfer from C-H donors to C acceptor sites. Enthalpies of hydride addition and enthalpies of activation. Comparison with C...H...C proton transfer. An ab initio study.

Enthalpies of addition of hydride ion to eleven carbonyl acceptors (X-CHO), two conjugate addition sites (X-CH=CH2; X = CHO, NO2), eight carbenium ion acceptors, fulvene, borane, and SiH3(+) were calculated at the MP2/6-311+G level. Correlation between calculated and experimental enthalpies of addition of hydride ion is excellent. Transition states (ts) for the identity hydride transfers between the acceptors and their corresponding hydride adducts (hydride donors) were also calculated. The carbonyl and fulvene reactions have transition states with one imaginary frequency: the hydrogen transfer coordinate. The carbenium ions, borane, and SiH3(+) gave not transition states but stable compounds upon addition of the hydride donor. Computational differences between these hydride transfers and previously reported proton transfers include shorter partial C...H bonds and a tendency toward bent C...H...C angles for the hydride transfer ts and addition compound structures, particularly when a bent geometry improves interactions elsewhere in the structure. These and other differences are explained by modeling the hydride transfer ts and addition compounds as two-electron, three-center systems involving the transfer termini and the shared hydrogen but the proton transfer ts structures as four-electron, three-center systems. Charge and geometry measures suggest transition states in which these features change synchronously, again in contrast to many proton transfer reactions. For the X-CHO set, polar effects dominate enthalpies of hydride addition, with resonance effects also important for resonance donors; these preferentially stabilize the acceptor, reducing its hydride ion affinity. Activation enthalpies are dominated by resonance stabilization of the acceptors, greatly attenuated in the transition states.

Dye-sensitized photooxygenation of the C=N bond. 5. substituent effects on the cleavage of the C=N bond of C-aryl-N-aryl-N-methylhydrazones.

The title compounds are cleaved cleanly at the C=N bond by singlet oxygen ((1)O(2), (1)Delta(g)) yielding arylaldehydes and N-aryl-N-methylnitrosamines. These reactions take place more rapidly at -78 degrees C than at room temperature. The effects of substituent variation at both the C-aryl and N-aryl groups were studied using a competitive method. Good correlations of the resulting rate ratios with substituent constants (sigma(-) or sigma(+)) were obtained yielding small to very small rho values indicative of small to very small changes in charge distribution between the reactant and the rate determining transition state. Electron withdrawing groups on the C-aryl moiety retard reaction somewhat by preferential stabilization of the hydrazone. Electron donors on the other hand slightly stabilize the rate determining transition state. Substituents on the N-aryl group have almost no effect. Inhibition by 3,5-di-tert-butylphenol was not observed showing that free (uncaged) radical intermediates are not involved in the mechanism. We postulate a mechanism in which the initial event is exothermic electron transfer from the hydrazone to (1)O(2) leading to an ion-radical caged pair. Subsequent covalent bond formation between the hydrazone carbon and an oxygen atom is rate controlling. The transition state for this step also has a lower enthalpy than the starting reactants, but the free energy of activation is dominated by a large negative TDeltaS++term leading to the negative temperature dependence. Direct formation of a C-O bond in the initial step is not unambiguously ruled out. Subsequent steps lead to C-N cleavage.

Identity proton-transfer reactions from C-H, N-H, and O-H acids. An ab initio, DFT, and CPCM-B3LYP aqueous solvent model study.

Identity proton-transfer reactions between 21 acids, Y-X-H, and their conjugate bases, (-)X-Y, were studied according to the reaction scheme, Y-X-H + (-)X-Y --> (Y-X-H...(-)X-Y)(cx) --> [Y-X...H...X-Y](ts) --> (Y-X..H-X-Y)(cx) --> Y-X(-) + H-X-Y, where cx indicates an ion-molecule complex and ts indicates the proton-transfer transition state. All species were optimized at the MP2/6-311+G level, and these geometries were used for single-point calculations by other methods: coupled-cluster, DFT (gas phase), and a polarizable continuum aqueous solvent model (COSMO). All methods gave enthalpies of deprotonation which correlate well with experimental measurements of deltaH(ACID) (gas) or pK(a) (aq). Calculated gas-phase enthalpies of deprotonation (deltaH(ACID)) and enthalpies of activation (deltaH(#)) are poorly correlated except for small, carefully selected sets. This result stands in contrast to the many aqueous phase Brönsted correlations of kinetic and equilibrium acid strength. On the other hand, gas-phase enthalpies of complexation and deltaH(#) are well correlated, indicating that factors which stabilize the transition state are at work in the bimolecular ion-molecule complex although to a smaller degree. We infer that intermoiety electrostatic and other interactions, similar within the complex and the transition state, but absent in the separated reactants (products), cause the lack of correlation between deltaH(ACID) and the other two quantities. Such differences are strongly attenuated in water because reactants and products do interact with polar/polarizable matter (the solvent) if not with each other. Charge distributions (NPA) were computed, allowing calculation of Bernasconi's "transition state imbalance parameter". Such measures provide intuitively satisfactory trends, but only if the reaction termini, X, are kept the same. As X is made more electronegative, the magnitude of the apparent imbalance increases, a result of greater negative charge on X in the transition state. This result gives additional support for the importance of the ion-triplet structure, [YX(-)...H(+)...(-)XY], to the stability of the transition state. Additional qualitative support for this conclusion is provided by the inverse relationship between the activation barrier and the charge on the in-flight hydrogen in the transition state, and by the dominance of polar over resonance substituent effects on the stability of the transition state. Calculations also show that the "nitroalkane anomaly", well established in solution, does not exist in the gas phase. The COSMO model partly reproduces this anomaly and performs adequately except when strong, specific intermolecular forces such as hydrogen bonding between solvent and anions are important.