A variational transition state theory description of periselectivity effects on cycloadditions of ketenes with cyclopentadiene

The reaction of cycloaddition of ketene and cyclopentadiene presents experimentally a competing mechanism where the branching ratio between the Woodward?CHoffmann allowed [4+2] and forbidden [2+2] cycloaddition product is 4.56?at ?20?°C, but because the minimum energy path misses the [2+2] product altogether, it has been claimed to lie beyond the scope of transition state theory. In this paper, a variational transition state theory study on this reaction is presented. It is found that the minimum energy path affording the [4+2] product travels through a potential energy plateau very close to the minimum energy path that describes the interconversion between both cycloaddition products, allowing the transfer between both and the direct formation of the forbidden [2+2] product, in this way acting as a means to circumvent the Woodward?CHooffmann rules. Within the domain of the competitive canonical unified statistical theory, a value for the branching ratio in very good agreement with experiment is computed.     

Stereoselectivity, periselectivity, and regioselectivity in the cycloadditions of 8-(p-chlorophenyl)-8-azaheptafulvene with cyclopentadiene and fulvenes

The stereoselectivity, periselectivity, and regioselectivity in the cycloaddition reactions of 8-(p-chlorophenyl)-8-azaheptafulvene with cyclopentadiene and symmetrical/unsymmetrical fulvenes is described.     

Studies on stereoselective [2+2] cycloadditions between N,N-dialkylhydrazones and ketenes

Staudinger-like cycloadditions between chiral, non-racemic N,N-dialkylhydrazones 1 and functionalized ketenes constitute an efficient methodology for the stereoselective construction of the beta-lactam ring. The potential for fine tuning of the dialkylamino auxiliary structure, the availability of a high-yielding deprotection method for the release of the free azetidinones, and the high thermal and chemical stability of hydrazones as N-dialkylamino imines are highlighted as the key elements for the success of the strategy. This last aspect is of particular importance concerning generality: even hydrazones from easily enolizable aldehydes or from formaldehyde reacted to afford the corresponding cycloadducts with high chemical and stereochemical yields. The syntheses of the beta-amino-alpha-hydroxyacids (2R,3S)-phenylisoserine (42) and (2R,3S)-norstatin (45) were accomplished as illustrative examples of the synthetic utility of this procedure. A model system for the cycloaddition of g series auxiliaries was studied by ab initio computational methods. The collected results support a two-step mechanism through zwitterionic intermediates, and explain the observed absolute and relative stereochemistry in terms of the preferred outward cycloaddition to the Re face of the hydrazone.     

Acid-catalyzed aza-Diels-Alder versus 1,3-dipolar cycloadditions of methyl glyoxylate oxime with cyclopentadiene

The acid-catalyzed 1,4- and 1,3-cycloadditions between methyl glyoxylate oxime (1) and cyclopentadiene were investigated using various Lewis and/or Bronsted acids at different temperatures in dichloromethane as solvent. Besides the expected new adducts, (±)-methyl [(3-exo)-2-hydroxy-2-azabicyclo[2.2.1]hept-5-ene]-3-carboxylate (2) and (±)-methyl [(3-endo)-2-hydroxy-2-azabicyclo[2.2.1]hept-5-ene]-3-carboxylate (3), a third adduct, (±)-methyl (1R,4R,5R)-(2-oxa-3-azabicyclo[3.3.0]oct-7-ene)-4-carboxylate (4), whose formation can be explained by a 1,3-dipolar cycloaddition, was obtained. Yields and product ratios were found to be more dependent on the catalyst than on the temperature; these results and the stereochemistry of the adducts, confirmed by spectroscopic data (¹H and ¹³C NMR) and by X-ray crystallography, were used to analyze and propose a mechanistic explanation for both cycloadditions.     

Intramolecular [2 + 2]cycloadditions of dialkylketenes with alkenes. Regiochemistry of intramolecular [2+2]cycloadditions of ketenes with alkenes

Unsaturated dialkylketenes 7a, 7b and 7c undergo intramolecular [2 + 2]cycloadditions to give 8a (45%), 9b (23%) and 9c (45%). Intramolecular cycloadditions of dialkylketenes give higher yields than intramolecular cycloadditions of monoalkylketenes, even though dialkylketenes are less reactive than monoalkylketenes. An intramolecular competition experiment with ketene 17 establishes that trans-alkenes are approximately 33 times more reactive than cis-alkenes in intramolecular cycloadditions. Ketene 36 furnishes 22% of the expected bicyclo[3.2.0]heptanone 37 and 28% of bicyclo[3.1.1]heptanone 38.     

Catalyst and ring size effects on periselectivity of oxonium ylide rearrangements

Diazoketones were subjected to carbene-transfer with Rh(II) or Cu(II) catalysts to probe the selectivity for rearrangement via five- or six-membered oxonium ylides. 4,5-Bis(benzyloxy) and 4-allyloxy-5-benzyloxy substrates 3a,b showed a large preference for rearrangement via the five-membered ylide under all conditions. However, a sharp divergence was seen with 5-allyloxy-4-benzyloxy substrate 3c, which underwent predominantly a [2,3]-shift to pyran 5c via the six-membered ylide with Cu(II) catalysis and a [1,2]-shift to furan 4c via the five-membered ylide with Rh(II) catalysis.     

Substituent effects on the reversibility of furan-maleimide cycloadditions

The effects of furan and maleimide substitution on the dynamic reversibility of their Diels-Alder reactivity have been investigated computationally and by (1)H NMR spectroscopy. Furan and furan derivatives bearing methoxy, methyl, or formyl groups at their 2- or 3-positions were investigated with maleimide and maleimide derivatives bearing N-methyl, N-allyl, and N-phenyl substituents. Computational predictions indicate that electronic and regiochemical effects of furan substitution significantly influence their Diels-Alder reactivity with maleimide, with reaction free energies of exo adduct formation ranging from ΔG = -9.4 to 0.9 kcal/mol and transition state barriers to exo adduct formation ranging from ΔG(?) = 18.9 to 25.6 kcal/mol. Much less variation was observed for the reactivity of N-substituted maleimide derivatives and furan, with reaction and transition state free energies each falling within a range of 1.1 kcal/mol. Dynamic exchange experiments monitored by (1)H NMR spectroscopy support computational predictions. The results indicate the reactivity and reversibility of furan-maleimide cycloadditions can be tuned significantly through the addition of appropriate substituents and have implications in the use of furan and maleimide derivatives in the construction of thermally responsive organic materials.     

NHC-catalyzed enantioselective [2 + 2] and [2 + 2 + 2] cycloadditions of ketenes with isothiocyanates

The enantioselective N-heterocyclic carbene-catalyzed formal [2 + 2] and [2 + 2 + 2] cycloaddition of ketenes and isothiocyanates were developed. Reaction with N-aryl isothiocyanates at room temperature favors the [2 + 2] cycloaddition, while reaction with N-benzoyl isothiocyanates at -40 °C favors the [2 + 2 + 2] cycloaddition.     

Theoretical rate constants and kinetic isotope effects in the reaction of methane with H, D, T, and Mu atoms

The rate constants and kinetic isotope effects of the reaction of methane with four isotopes of hydrogen, protium (H), deuterium (D), tritium (T), and muonium (Mu), were studied using variational transition state theory with multidimensional tunneling on an analytical potential energy surface, PES-2002, previously constructed by our group. For the four isotopes, our kinetics results agree reasonably with available experimental measurements, improving previous theoretical results that used different potential energy surfaces and/or theoretical approaches. In the comparison of the reactivity between protium and muonium, which is the most severe test of the surface and theoretical method due to the large mass difference between the two isotopes, some sources of discrepancy between theory and experiment were analyzed. These were the zero-point energy, tunneling effect, and the role of the reactivity from methane excited vibrational states.     

Quantitative 2H NMR spectroscopy. 1. Thermodynamic H/D isotope effects in N,N-dimethylformamide and cyclopentadiene molecules

A new method for quantification of the relative distribution of deuterium in molecules is proposed. The technique is based on the lineshape analysis in the ²H NMR spectra obtained at the natural abundance level of deuterium with allowance for inhomogeneity of the magnetic field. The equilibrium thermodynamic H/D isotope effects for hindered rotation about the C—N bond in the N,N-dimethylformamide molecule and for prototropic exchange in the cyclopentadiene molecule were determined. The results obtained agree with those of DFT calculations of the vibrational energies.     

Hydrogen isotope effects and mechanism of aqueous ozone and peroxone decompositions

Hydrogen peroxide exalts the reactivity of aqueous ozone by reasons that remain obscure. Should H2O2 enhance free radical production, as it is generally believed, a chain mechanism propagated by (.OH/.O2-) species would account for O3 decomposition rates in neat H2O, HR-O3, and in peroxone (O3 + H2O2) solutions, HPR-O3. We found, however, that: (1) the radical mechanism correctly predicts HR-O3 but vastly overestimates HPR-O3, (2) solvent deuteration experiments preclude radical products from the (O3 + HO2-) reaction. The modest kinetic isotope effect (KIE) we measure in H2O/D2O: HR-O3/DR-O3 = 1.5 +/- 0.3, is compatible with a chain process driven by electron- and/or O-atom transfer processes. But the large KIE found in peroxone: HPR-O3/DPR-O3 = 19.6 +/- 4.0, is due to an elementary (O3 + HO2-) reaction involving H-O2- bond cleavage. Since the KIE for the hypothetical H-atom transfer: O3 + HO2- HO3. +.O2-, would emerge as a KIE1/2 factor in the rates of the ensuing radical chain, the magnitude of the observed KIE must be associated with the hydride transfer reaction that yields a diamagnetic species: O3 + HO2- HO3- + O2. HO3-/H2O3 may be the bactericidal trioxide recently identified in the antibody-catalyzed addition of O2(1Deltag) to H2O.     

A mechanism of addition of a new aromatic electrophile,nitrobenzofuroxan, to cyclopentadiene

The reaction mechanisms of cycloaddition of nitrobenzofuroxan to cyclopentadiene are studied using DFT calculations at the B3LYP/6-31G* level in the gas phase and with account of the solvation effects. The reaction follows a three-step mechanism and includes the formation of a prereaction donor-acceptor complex, endo [4+2] cycloaddition with inverse electron demands (IED), and [3,3]-sigmatropic rearrangement to the final endo [2+4] adduct. No formation of stable bipolar σ-complexes on the minimum-energy reaction pathways occurs.     

Theoretical study of the mechanism of the 1,3-dipolar cycloadditions

By means of the MINDO/3 method the potential energy hypersurfaces for the 1,3-dipolar cycloadditions of carbonyl and azomethine ylides to ethylene have been studied. In the first place, the synchronous formation of the two new sigma bonds has been considered. In the second place, the asynchronous region of the surface has been explored. The asynchronous mechanism appears to be more favourable, there being two transition states and an intermediate. Finally, the physical meaning of the results obtained is discussed.     

Electrophilic fluorination of aromatic compounds with NF type reagents: kinetic isotope effects and mechanism

H/D Isotope effects in fluorination of aromatic compounds with NF type reagents have been studied to reveal the reaction mechanism. The results obtained are consistent with a polar S_EAr mechanism. Small deuterium isotope effects (k_H/k_D = 0.86-0.99) show that decomposition of a Wheland-type intermediate is not rate determining. The first example of a 1,2-hydrogen shift accompanying electrophilic fluorination of arenes has been observed in the fluorination of 1,3,5-trideuterobenzene.