DFT study on [4+2] and [2+2] cycloadditions to [60] fullerene

The functionalisation of C₆₀ fullerene with 2,3-dimethylene-1,4-dioxane (I) and 2,5-dioxabicyclo [4.2.0]octa-1(8),6-diene (II) was investigated by the use of density functional theory calculations in terms of its energetic, structural, field emission, and electronic properties. The functionalisation of C₆₀ with I was previously reported experimentally. The I and II molecules are preferentially attached to a C—C bond shared and located between two hexagons of C₆₀ via [4+2] and [2+2] cycloadditions bearing reaction energies of ?15.9 kcal mol^?1 and ?72.4 kcal mol^?1, respectively. The HOMO-LUMO energy gap and work function of C₆₀ are significantly reduced following completion of the reactions. The field electron emission current of the C₆₀ surface will increase after functionalisation of either the I or II molecule.     

[2+2]-cycloadditions of cyclopentyne

Cyclopentyne, as generated from dibromomethylenecyclobutane, a formerly unknown cyclopentyne source, undergoes [2+2]-cycloadditions with various substituted olefins yielding bicyclo[3.2.0]hept-1(5)-ene derivatives.     

Thermal behavior of [2.1.1]propellane: a DFT/ab initio study

Density functional and ab initio molecular orbital calculations have been used to search for the low energy path of the thermal isomerization of [2.1.1]propellane 1. Three reaction modes were considered: ring opening of the bicyclo[1.1.0]butane unit in 1 to give 1,2-dimethylenecyclobutane 21, opening of the four-membered ring of 1 to afford 1,3-dimethylenecyclobutane 20, and breaking of the [2.1.1]propellane central bond and one of the bicyclo[1.1.0]butane side bonds to form carbene 17. At the CAS(12,12)PT2N/6-31G(d) level of theory, the activation barrier of the latter route was lowest in energy. Further investigation of this process at the QCISD(T)/6-311G(d,p)//QCISD/6-31G(d) and B3PW91/6-311G(d,p)// B3PW91/6-311G(d,p) level of theory indicated that the barrier of isomerization of 1 --> 17 amounts to 29 kcal/mol and that 17 is stabilized by hydrogen migration to give dienes 18 and 19.     

Stereochemistry of the [2+4] cycloaddition of cyclopentyne

The [2+4] cycloaddition of cyclopentyne with a pair of diastereomeric 1,3-dienes is found to occur with high stereoselectivity. The results support the applicability of the principles of orbital symmetry even in the case of this exceedingly reactive dienophile.     

DFT and ab initio study on the reaction mechanism of CH2SH + O2

The mechanism for the CH₂SH + O₂ reaction was investigated by DFT and ab initio chemistry methods. The geometries of all possible stationary points were optimized at the B3LYP/6-311+G(d,p) level, and the single point energy was calculated at the CCSD(T)/cc-pVXZ(X = D and T), G3MP2 and BMC-CCSD levels. The results indicate that the oxidation of CH₂SH by O₂ to form HSCH₂OO is a barrierless process. The most favorable channel is the rearrangement of the initial adduct HSCH₂OO (IM1) to form another intermediate H₂C(S)OOH (IM3) via a five-center transition state, and then the C–O bond fission in IM3 leads to a complex CH₂S. . .HO₂ (MC1), which finally gives out to the major product CH₂S + HO₂. Due to high barriers, other products including cis- and trans-HC(O)SH + HO could be negligible. The direct abstraction channel was also determined to yield CH₂S + HO₂, with the barrier height of 22.3, 18.1 and 15.0 kcal/mol at G3MP2, CCSD(T)/cc-pVTZ and BMC-CCSD levels, respectively, it is not competitive with the addition channel, in which all stationary points are lower than reactant energetically. The other channels to produce cis- and trans-CHSH + HO₂ are also of no importance.     

An ab initio study on the allene-isocyanic acid and ketene-vinylimine [2 + 2] cycloaddition reaction paths

The reaction paths of [2 + 2] cycloadditions of allene (H2C=C=CH2) to isocyanic acid (HN=C=O) and ketene (H2C=C=O) to vinylimine (H2C=C=NH), leading to all the possible 14 four-membered ring molecules, were investigated by the MP2/aug-cc-pVDZ method. In the two considered reactions, the 2-azetidinone (beta-lactam) ring compounds were predicted to be the most stable thermodynamically in the absence of an environment. Although 4-methylene-2-azetidinone is the most stable product of the ketene-vinylimine cycloaddition, its activation barrier is higher than that for 4-methylene-2-iminooxetane by ca. 6 kcal/mol. Therefore, the latter product can be obtained owing to kinetic control. The activation barriers in the allene-isocyanic acid reactions are quite high, 50-70 kcal/mol, whereas in the course of the ketene-vinylimine cycloaddition they are equal to ca. 30-55 kcal/mol. All the reactions studied were found to be concerted and mostly asynchronous. Simulation of the solvent environment (toluene, tetrahydrofuran, acetonitrile, and water) by using Tomasi's polarized continuum model with the integral equation formalism (IEF-PCM) method showed the allene-isocyanic reactions remained concerted, yet the activation barriers were somewhat higher than those in the gas phase, whereas the ketene-vinylimine reactions became stepwise. The larger the solvent dielectric constant, the lower the activation barriers found. The lowest-energy pathways in the gas phase and in solvent were confirmed by intrinsic reaction coordinate (IRC) calculations. The atoms in molecules (AIM) analysis of the electron density distribution in the transition-state (TS) structures allowed us to distinguish pericyclic from pseudopericyclic from nonplanar-pseudopericyclic types of reactions.     

Intramolecular ketenimine-ketenimine [2 + 2] and [4 + 2] cycloadditions

Bis(ketenimines), in which the two heterocumulenic functions are placed in close proximity on a carbon skeleton to allow their mutual interaction, show a rich and not easily predictable chemistry. Intramolecular [2 + 2] or [4 + 2] cycloadditions are, respectively, observed when both ketenimine functions are supported on either ortho-benzylic or 2,2'-biphenylenic scaffolds. In addition, nitrogen-to-carbon [1,3] and [1,5] shifts of arylmethyl groups in N-arylmethyl-C,C-diphenyl ketenimines are also disclosed.     

CpRuCl- and CpCo-catalyzed or mediated cyclotrimerizations of alkynes and [2+2+2] cycloadditions of alkynes to alkenes: A comparative DFT study

Computational methods have been used to better understand both the CpRuCl- and CpCo-catalyzed and mediated cyclotrimerization of alkynes and the [2+2+2] cycloaddition of alkynes to alkenes. These studies have allowed more accurate mechanisms to be proposed for each of these transformations and for some previously proposed intermediates to be discarded. The mechanistic rationale of these processes depends on the nature of the metal, ligands and substrate partners.     

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.     

Proton as the simplest of all catalysts for [2 + 2] cycloadditions: DFT study of acid-catalyzed imine metathesis

The mechanism of imine metathesis was studied as a prototype reaction for the impact that heteroatom substitution has on thermally forbidden [2 + 2] addition reactions using high-level density functional theory in combination with a continuum solvation model. The intuitively expected high activation barriers were confirmed for N-alkyl- and N-aryl-substituted imine reactants with transition state free energies of 78.8 and 68.5 kcal/mol, respectively, in benzene. The computed reaction energy profiles were analyzed to discover possible strategies for lowering the transition state energy. Protonation of the imine nitrogen was proposed as a possible catalytic route and was explicitly modeled. The computed reaction energy profile shows that protonation of one of the imine reactants has an enormous effect on the overall rate of metathesis and lowers the activation barrier by as much as 37.3 and 30.6 kcal/mol for the N-alkyl and N-aryl reactants, respectively. These results suggest that acid-catalyzed imine metathesis should be amenable at elevated temperatures. Furthermore, the protonation of both reactants of the metathesis reaction is predicted to be not productive owing to electrostatic repulsion of the reactants, thus suggesting that there should be an optimum pH for the catalytic turnover. A detailed analysis of the catalytic mechanism is presented, and the primary driving force for the catalysis is identified. Upon protonation of the imine nitrogen, the key [2 + 2]-addition step becomes asynchronous and one of the two intermolecular N-C bonds is formed before traversing the transition state, resulting in a substantial net decrease of the overall energy requirement. The general applicability of this intuitively understandable mechanism for designing structural features for lowering the energy of transition state structures is explored.     

Ruthenium-catalyzed [2 + 2] cycloadditions of ynamides

Ruthenium-catalyzed [2 + 2] cycloadditions between norbornene and ynamides were investigated. The ynamide moiety was found to be compatible with the ruthenium-catalyzed cycloaddition conditions, giving the corresponding cyclobutene cycloadducts in moderate to good yields (up to 97%). [reaction: see text]     

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.     

Regioselectivity in iron-catalyzed [2+2+1] cycloadditions: a DFT investigation of substituent effects in 1,4-diazabutadienes

The transition-metal-catalyzed [2+2+1] cycloaddition reaction of 1,4-diazabutadienes, in which the imine-carbon atoms are part of an oxazine ring system, with ethylene and carbon monoxide leads to the regioselective formation of pyrrolidinone derivatives. To explain this regioselectivity, the transition states and intermediates of the rate-determining step of the catalysis are determined by high-level DFT calculations. The experimentally observed regioselectivity is consistent with the lower activation energy of the addition of ethylene towards the carbon atom next to the oxazine oxygen atom. Furthermore, the activation barrier of a conceivable back reaction is higher for the intermediates with the experimentally observed regioselectivity. These thermodynamic and kinetic arguments at first sight appear to be confirmed by the calculated NPA charges in the transition states, which reveal that the differences in these charges are greatest for those transition states that lead to the formation of the energetically favored transition structures. Nevertheless, calculations of analogous transition structures and reaction products starting from 1,4-diazabutadienes with a 2-fluoro, 2-hydroxo or 2-amino substituent revealed that the regioselectivity is not determined by the electronegativity of the heteroatom and thus by the differences in the NPA charges or the resulting Coulombic interactions in the transition structures. The main reason for the observed regioselectivities is the pi-donor ability of the substituent to contribute to a delocalized pi system incorporating the adjacent imine moiety. The increasing pi-donor capability results in decreased reactivity of this moiety and increases the (relative) reactivity of the second imine group. This effect can even overcompensate for strong intramolecular Coulombic attractions in the transition structures.     

Rhodium catalysed [2+2+2] cycloadditions of acetylenes

Wilkinson's catalyst RhCl(PPh₃)₃ is an effective catalyst (0.5 – 2 mole %) for the rapid intermolecular trimerisation of 1,6-heptadiynes with monoacetylenes under mild conditions.     

Silver-catalyzed [2 + 2] cycloadditions of siloxy alkynes

We have described the first [2 + 2] cycloadditions of siloxy alkynes with a range of unsaturated carbonyl compounds. The reactions are efficiently promoted by substoichiometric amount of silver trifluoromethanesulfonimide and display excellent regio- and diastereoselectivity combined with a broad substrate scope. Our studies have established unambiguously the stepwise mechanism of this process and provided evidence for a novel role of silver in the catalytic cycle of the reaction, which involves silver-based complexation and activation of siloxy alkyne toward the subsequent 1,4-addition.     

Frontier-orbital analyses of ketene [2+2] cycloadditions

Twelve kinds of ketene [2+2] cycloadditions have been investigated by ab initio calculations. They are composed of four ketenes (Y–HC=C=O, Y=H, NH₂, Cl, and CN) and three isoelectronic ketenophiles (ethylene, methylenimine, and formaldehyde). All the transition state geometries obtained here are not different significantly, but the extent of formation of two covalent bonds differs appreciably. The difference is attributable to the degree of the charge transfer interactions. One is the interaction from the π orbital and/or the lone pair orbital of a ketenophile to the LUMO of a ketene (dominant charge transfer, CT1). The other is that from the HOMO of the ketene to the π* orbital of the ketenophile (second dominant charge transfer, ct1). CT1 contributes to the formation of only one covalent bond, and ct1 does to the formation of the other. This independent function is characteristic of ketene [2+2] cycloadditions. They are not concerned with the orbital phase. We also have examined Fukui's postulate that the deformation of particular frontier orbitals causes the reaction progress. The role has been verified both by configuration analyses along the intrinsic reaction coordinate of the ketene-ethylene reaction and by the examination of distortions of frontier-orbital shapes along the low-frequency vibrational modes. Received: 25 June 1998 / Accepted: 28 August 1998 / Published online: 11 November 1998     

Synthesis of macrocycles via cobalt-mediated [2 + 2 + 2] cycloadditions

We investigated the formation of macrocycles from alpha,omega-diynes in cobalt-mediated co-cyclotrimerization reactions. Long-chain alpha,omega-diynes underwent metal-mediated [2 + 2 + 2] cycloadditions with nitriles, cyanamides, or isocyanates in the presence of CpCo(CO)2 (Cp = cyclopentadienide) to yield pyridine-containing macrocycles, i.e., meta- and para-pyridinophanes, such as 5m/5p, 35m/35p, and 41m/41p. The regioselectivity of these reactions was affected by the length and type of linker unit between the alkyne groups, as well as by certain stereoelectronic factors. An analogous alpha,omega-cyano-alkyne, 28, combined with an alkyne to yield two isomeric meta-pyridinophanes, such as 5m and 29m, and an ortho cycloadduct (benzannulation product), such as 29o. We developed a reaction protocol for these cobalt-based [2 + 2 + 2] cycloadditions that involves markedly improved conditions such that this process offers a convenient, flexible synthetic approach to macrocyclic pyridine-containing compounds. For example, diyne 6 reacted with p-tolunitrile in 1,4-dioxane to give 7p and 7m (7:1 ratio) in 87% yield at a moderate temperature of ca. 100 degrees C in 24 h without photoirradiation or syringe-pump addition. Isocyanates were also effective reactants, as exemplified by the formation of 44p almost exclusively (44p:44m > 50:1) in 64% yield from diyne 8 and 2-phenylethylisocyanate. By using this improved protocol we were able to co-cyclotrimerize long-chain alpha,omega-diynes with alkynes in certain cases to demonstrate a successful macrocyclic variant of the Vollhardt reaction. For instance, diyne 6 reacted with dipropylacetylene to give paracyclophane 57p and benzannulene 57o (2:1 ratio) in 29% yield.     

Ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes

The studies of remote substituent effects in controlling regio- and stereoselectivities in chemical reactions provide important information in understanding long-range stereoelectronic effects. The effect of remote substituents on ruthenium-catalyzed [2 + 2] cycloadditions of 2-substituted norbornenes has been investigated. The cycloadditions occurred at room temperature in excellent yields, and regioselectivities of 1.2:1 to 7.5:1 were observed with various 2-substituted norbornenes.