Palladium-catalyzed addition of alkynes to cyclopropenes

The palladium catalyzed coupling of alkynes and cyclopropenes provides a powerful method for the synthesis of alkynylcyclopropanes, proceeding under mild conditions in the presence of many functional groups (such as esters, carboxylic acids, aldehydes, and alcohols).     

Palladium-catalyzed addition of alkynes to cyclopropenes: an entry to stereodefined alkynylcyclopropanes

The Herrmann-Beller (H-B) phosphapalladacycle catalyzed the addition of terminal alkynes to unsymmetrical gem-disubstituted cyclopropenes to give alkynylcyclopropanes as single diastereomers in good to excellent yields. The stereofacial discrimination at the approach of the bulky alkynylpalladium species is believed responsible for the diastereoselectivity control of the addition reaction.     

Mechanism of the palladium-catalyzed addition of arylboronic acids to enones: a computational study

The palladium(II)-catalyzed addition of arylboronic acids to β,β-disubstituted enones has been investigated with the BP86 density functional. The results show that the mechanism requires three steps: transmetalation, alkene insertion, and protonation. The alkene insertion is the rate-determining step. For unactivated alkenes, the Heck-type β-hydride elimination is more favored than protonation.     

Acyl radical addition to benzene and related systems—a computational study

The addition of the acetyl radical to benzene, aniline, trifluoromethylbenzene and naphthalene has been investigated using DFT calculations. Addition to benzene is calculated to have an energy barrier of 63.6 kJ mol⁻¹ at the BHandHLYP/6-311G(d,p)+ZPE level of theory. This reaction is associated with simultaneous SOMO→π^∗ and π→SOMO interactions with the latter interaction dominating, suggesting that acetyl reacts predominantly as an electrophilic radical in its interaction with benzene. Addition to the ortho and para positions of aniline is calculated to be slightly less favourable, while attack at the meta position is predicted to be unaffected in relation to the chemistry involving benzene. Inclusion of the electron-withdrawing substituent, trifluoromethyl, is predicted to accelerate reactions slightly at the ortho and para positions, while attack at the C1 position of naphthalene is calculated to involve a barrier of 50.3 kJ mol⁻¹ (BHandHLYP/6-311G(d,p)+ZPE).     

Concerted and stepwise reaction mechanisms for the addition of ozone to acetylene: a computational study

The mechanism of the reaction between acetylene and ozone to form a primary ozonide (POZ) in the gas phase has been studied theoretically. The concerted pathway, HCCH + O3 --> POZ, proceeds via a biradicaloid transition state TS0. The stepwise pathway is a three-step reaction, HCCH + O3 --> M1 --> M2 --> POZ, involving two biradical TSs and two biradical intermediates M1 and M2. The segment of the global potential energy surface (PES) for the concerted pathway is characterized as a R-PES, which is obtained from the restricted (R) density functional theory and Hartree-Fock-based methods. The RDFT and RHF solutions of TS0 and O3 are unstable toward spin-symmetry breaking. The wave function instability for TS0 and O3 results in a discontinuity between the R-PES and the region of the global PES encompassing the biradical TSs and the intermediates of the stepwise pathway, which are characterized with unrestricted (U) methods. The global PES is characterized separately as an U(R)-PES using a combination of the R and U methods. Several different values of barriers for the concerted pathway and the energy of concert (Ec) can be estimated due to complications arising from the discontinuity between the R- and the U(R)-PES and the existence of two different RDFT and UDFT O3 equilibrium geometries. RCCSD(T)//RDFT predicts a barrier of 8.2 kcal/mol. U(R)CCSD(T)/U(R)DFT predicts a barrier of 13.8 kcal/mol for the concerted and 15.3 kcal/mol for the stepwise pathway. Comparison between the R-PES barrier to the concerted pathway and the U(R)-PES barrier to the stepwise pathway suggests the former to be the only significant mechanism. Consideration of the energy difference between TS1, the TS for the first step of the stepwise mechanism, and TS0 within the global PES leads to a significantly smaller Ec. Geometry optimization with CASSCF and energy point calculations with MRMP2 are employed to characterize TS0 and TS1. MRMP2//CASSCF predicts the energy level of TS1 to be higher than that of TS0 by 2 kcal/mol. Analysis of experimental and computational data based on the low estimate of Ec shows that the possibility of the stepwise pathway being a secondary channel at elevated temperatures cannot be ruled out.     

Dichlorocarbene Addition to

In contrast to the terminal phosphinidene complex PhPW(CO)(5) (2), which adds to [5]metacyclophane (1) in a 1,4-fashion, dichlorocarbene preferentially adds in a 1,2-fashion to the formal "anti-Bredt" type double bond of the aromatic ring of 1 to afford the norcaradiene 11b, which immediately rearranges to the bridged cycloheptatriene 12b and further by a [1,5] sigmatropic chlorine migration to the isomeric 13b as the first observable product. More slowly, the latter isomerizes via a dissociative mechanism to give 15b. A computational study supports the notion that the [1,5] chlorine migration in the rearrangement 12b --> 13b, for which an activation barrier of 70.2 kJ mol(-)(1) was calculated, is essentially concerted with minor charge separation. In contrast, the analogous [1,5] chlorine migration in the flat model compound 7,7-dichlorocycloheptatriene (12a) displays features of a dissociative pathway.     

A computational study on addition of Grignard reagents to carbonyl compounds

The mechanism of stereoselective addition of Grignard reagents to carbonyl compounds has been investigated using B3LYP density functional theory calculations. The study of the reaction of methylmagnesium chloride and formaldehyde in dimethyl ether revealed a new reaction path involving carbonyl compound coordination to magnesium atoms in a dimeric Grignard reagent. The structure of the transition state for the addition step shows that an interaction between a vicinal-magnesium bonding alkyl group and C=O causes the C-C bond formation. The simplified mechanism shown by this model is in accord with the aggregation nature of Grignard reagents and their high reactivities toward carbonyl compounds. Concerted and four-centered formation of strong O-Mg and C-C bonds was suggested as a polar mechanism. When the alkyl group is bulky, C-C bond formation is blocked and the Mg-O bond formation takes precedence. A diradical is formed with the odd spins localized on the alkyl group and carbonyl moiety. Diradical formation and its recombination were suggested to be a single electron transfer (SET) process. The criteria for the concerted polar and stepwise SET processes were discussed in terms of precursor geometries and relative energies.     

A copper-catalyzed method for the facially selective addition of grignard reagents to cyclopropenes

A Cu-catalyzed method for the addition of Grignard reagents to 1-alkyl-3-hydroxymethylcyclopropenes and their MOM ethers is described. The face of addition is syn relative to the hydroxymethyl and alkoxymethyl groups. Excellent diastereoselectivity is observed for a range of alkyl, alkenyl, and alkynylmagnesium halides. The addition reactions create chiral all-carbon quaternary centers, and the cyclopropylmetals that are generated can be reacted with electrophiles to produce highly functionalized cyclopropanes.     

Radicals masquerading as electrophiles: a computational study of the intramolecular addition reactions of acyl radicals to imines

Ab initio calculations using 6-311G**, cc-pVDZ, and aug-cc-pVDZ, with (MP2, QCISD, CCSD(T)) and without (UHF) electron correlation, and density functional methods (BHandHLYP and B3LYP) predict that cyclization of the 5-aza-5-hexenoyl and (E)-6-aza-5-hexenoyl radicals proceed to afford the 5-exo products. At the CCSD(T)/cc-pVDZ//BHandHLYP/cc-pVDZ level of theory, energy barriers (deltaE(double dagger)) of 36.1 and 47.0 kJ mol(-1) were calculated for the 5-exo and 6-endo pathways for the cyclization of the 5-aza-5-hexenoyl radical. On the other hand, at the same level of theory, deltaE(double dagger) of 38.9 and 45.4 kJ mol(-1) were obtained for the 5-exo and 6-endo cyclization modes of (E)-6-aza-5-hexenoyl radical, with exothermicities of about 27 and 110 kJ mol(-1) calculated for the exo and endo modes, respectively. Under suitable experimental conditions, the 6-endo cyclization product is likely to dominate. Analysis of the molecular orbitals involved in these ring-closure reactions indicate that both reactions at nitrogen are assisted by dual orbital interactions involving simultaneous SOMO-pi* and LP-pi* overlap in the transitions states. Interestingly, the (Z)-6-aza-5-hexenoyl radical, that cannot benefit from these dual orbital effects is predicted to ring-close exclusively in the 5-exo fashion.     

Gold(I)-catalyzed addition of thiols and thioacids to 3,3-disubstituted cyclopropenes

Gold(I)-catalyzed reactions of thiols, thiophenols, and thioacids with 3,3-disubstituted cyclopropenes occur in a regioselective and chemoselective manner to produce either vinyl thioethers or primary allylic thioesters in good yields. A survey of commonly used gold(I) catalysts shows Echavarren's cationic gold(I) catalyst to be most tolerant of deactivation by sulfur. A novel digold with bridging thiolate complex is characterized by X-ray crystallography, shedding light on a possible deactivation pathway.     

Origins of stereoselectivity in the Diels-Alder addition of chiral hydroxyalkyl vinyl ketones to cyclopentadiene: a quantitative computational study

Modest basis set level MP2/6-31G(d,p) calculations on the Diels-Alder addition of S-1-alkyl-1-hydroxy-but-3-en-2-ones (1-hydroxy-1-alkyl methyl vinyl ketones) to cyclopentadiene correctly reproduce the trends in known experimental endo/exo and diastereoface selectivity. B3LYP theoretical results at the same or significantly higher basis set level, on the other hand, do not satisfactorily model observed endo/exo selectivities and are thus unsuitable for quantitative studies. The same is valid also with regard to subtle effects originating from, for example, conformational distributions of reactants. The latter shortcomings are not alleviated by the fact that observed diastereoface selectivities are well-reproduced by DFT calculations. Quantitative computational studies of large cycloaddition systems would require higher basis sets and better account for electron correlation than MP2, such as, for example, CCSD. Presently, however, with 30 or more non-hydrogen atoms, these computations are hardly feasible. We present quantitatively correct stereochemical predictions using a hybrid layered ONIOM computational approach, including the chiral carbon atom and the intramolecular hydrogen bond into a higher level, MP2/6-311G(d,p) or CCSD/6-311G(d,p), layer. Significant computational economy is achieved by taking account of surrounding bulky (alkyl) residues at 6-31G(d) in a low HF theoretical level layer. We conclude that theoretical calculations based on explicit correlated MO treatment of the reaction site are sufficiently reliable for the prediction of both endo/exo and diastereoface selectivity of Diels-Alder addition reactions. This is in line with the understanding of endo/exo selectivity originating from dynamic electron correlation effects of interacting pi fragments and diastereofacial selectivity originating from steric interactions of fragments outside of the Diels-Alder reaction site.     

Vibrational corrections to magneto-optical rotation: a computational study

Vibrational corrections to the Verdet constants of nine molecules (H2, N2, CO, H2O, CH4, benzene, toluene, p-xylene, and o-xylene) were calculated with pure density functional theory (DFT), hybrid DFT, and an approximate coupled-cluster theory. Comparisons are made for the accuracy of the vibrational averages among different methods and with respect to experimental data where available. It is found that vibrational corrections to magneto-optical rotation can be as large as 10% of the equilibrium value. Hybrid DFT with the B3LYP hybrid functional offers reasonable accuracy at a relatively inexpensive computational cost for accurate calculations of vibrationally averaged Verdet constants.     

Au-catalyzed isomerization of cyclopropenes: a novel approach to indene derivatives

AuPPh₃Cl/AgOTf-catalyzed reaction of cyclopropenes is found to be highly efficient, giving indene derivatives in high yields. The reaction is suggested to proceed through gold vinyl carbenoid intermediate.     

Trapping acrylamide by a Michael addition: A computational study of the reaction between acrylamide and niacin

Neurotoxic and carcinogenic acrylamide (ACR) is present in many food products. This finding spurred numerous studies for ACR scavengers. Niacin is putatively one of them because it reacts via Michael addition with ACR to form 1‐propanamide‐3‐carboxy pyridinium. Here, we study the mechanism and energetics of this reaction in aqueous solution by density functional theory. The CAM‐B3LYP and M06‐2X functionals with the 6‐31+G(d,p) basis set and implicit solvent were used. Single point calculations at the MP2 level with the same basis set were performed on optimized structures obtained at the M06‐2X level. Solvent effects comprehended both polarizable continuum model and solvation model density solvation models. The calculated NMR chemical shifts of 1‐propanamide‐3‐carboxy pyridinium are in agreement with experimental results. The theoretical study favors thermodynamically the formation of the adduct while the calculated activation energies turn out not to be too dissimilar from the ones measured for the alkylation reaction between ACR and 4(p‐nitrobenzyl)pyridine. © 2014 Wiley Periodicals, Inc.     

Monosilicon-substituted cyanoacetylene: a computational study

A detailed theoretical investigation of the [H,Si,C(2),N] potential energy surfaces including 28 minimum isomers and 65 interconversion transition states is reported at the Gaussian-3//B3LYP/6-31G(d) level. Generally, the triplet species lie energetically higher than the singlet ones. The former three low-lying isomers are linear HCCNSi 1 (0.00 kcal/mol), branched SiC(H)CN 12 (7.09 kcal/mol), and bent HNCCSi 7 (14.22 kcal/mol), which are separated by rather high barriers from each other and are kinetically very stable with the least conversion barriers of 32.6-70.5 kcal/mol. Two energetically high-lying isomers HCNCSi 3 (42.99 kcal/mol) and SiC(H)NC 13 (36.05 kcal/mol) are also kinetically stable with a barrier of 49.19 and 21.42 kcal/mol, respectively. Additionally, five high-lying isomers, that is, three chainlike isomers, HCCSiN 2 (55.17), HCSiNC 6 (47.80), HSiNCC 11 (78.83), and one three-membered ring isomer HN-cSiCC 19 (51.21), and one four-membered ring isomer cSiCN(H)C 27 (50.6 kcal/mol), are predicted to each have lower conversion barriers of 12-18 kcal/mol and can be considered as meta-stable species. All of the predicted 10 isomers could exist as stable or meta-stable intermediates under suitable conditions. Finally, the structural and bonding analysis indicate that the [H,Si,C(2),N] molecule contains various properties that are of chemical interest (e.g., silylene, SiC triple bonding, and conjugate SiN triple bonding and CC triple bonding, charge-transfer specie, planar aromatic specie, cumulate double bonding). This is the first detailed theoretical study on the potential energy surfaces of the series of hydrogenated Si,C,C,N-containing molecules. The knowledge of the present monohydrogenated SiC(2)N isomerism could provide useful information for more highly hydrogenated or larger Si,C(2),N-containing species.     

Coordination of methanol clusters to benzene: a computational study

Benzene-methanol cluster structures were investigated with theoretical chemistry methods to describe the microsolvation of benzene and the benzene-methanol azeotrope. Benzene-methanol (MeOH) clusters containing up to six methanol molecules have been calculated by ab initio [MP2/6-311++G(d,p)//MP2/6-31+G(d,p) + BSSE correction] method. The BSSE was found quite large with this basis set, hence, different extrapolation schemes in combination with the aug-cc-pVxZ basis sets have been used to estimate the complete basis set limit of the MP2 interaction energy [ΔE(MP2/CBS)]. For smaller clusters, n ≤ 3, DFT procedures (DFTB+, MPWB1K, M06-2X) have also been applied. Geometries obtained for these clusters by M06-2X and MP2 calculations are quite similar. Based on the MP2/CBS results, the most stable C(6)H(6)(MeOH)(3) cluster is characterized by a hydrogen bonded MeOH trimer chain interacting with benzene via π···H-O and O···H-C(benzene) hydrogen bonds. Larger benzene-MeOH clusters with n ≥ 4 consist of cyclic (MeOH)(n) subclusters interacting with benzene by dispersive forces, to be denoted by C(6)H(6) + (MeOH)(n). Interaction energies and cooperativity effects are discussed in comparison with methanol clusters. Besides MP2/CBS calculations, for selected larger clusters the M06-2X/6-311++G(d,p)//M06-2X/6-31+G(d,p) procedure including the BSSE correction was also used. Interaction energies obtained thereby are usually close to the MP2/CBS limit. To model the benzene-MeOH azeotrope, several structures for (C(6)H(6))(2)(MeOH)(3) clusters have been calculated. The most stable structures contain a tilted T-shaped benzene dimer interacting by π···H-O and O···H-C (benzene) hydrogen bonds with a (MeOH)(3) chain. A slightly less negative interaction energy results for a parallel displaced benzene sandwich dimer with a (MeOH)(3) chain atop of one of the benzene molecules.     

A computational study of the addition reaction of cyclopropenylidene with methyleneimine

The reaction mechanism between cyclopropenylidene and methyleneimine has been systematically investigated at the MP2/6–31+G* level of theory, including geometry optimization, vibrational analysis, and energy property for the involved stationary points on the potential energy surface. The energies of the different species are calculated by the single point energy calculations of CCSD(T)/6-31+G*//MP2/6-31+G* level. It was found that an important initial intermediate (INTA) characterized by spiro-compound structure has been located along the three pathways (1), (2R), and (2L) firstly. After that, another common intermediate (INTB) has been formed via TSB. At last, three different products possessing three- and four-membered ring characters have been obtained through corresponding reaction pathways. In the first reaction pathway (1), a three-membered ring alkyne compound has been obtained. As for the other two reaction pathways (2R) and (2L), the four-membered ring conjugated diene compound has been produced. As a result, the energy barrier of the rate-determining step of the pathway (1) is lower than that of the pathway (2R) and (2L), and the ultima product of pathway (2R) and (2L) is more stable than that of the pathway (1).     

The SAMP alkylation: a computational study

In a computational study of a stereoselective C-C bond formation, the SAMP alkylation, a previously proposed S(E)2'-front mechanism is evaluated taking into account all current experimental evidence. Using semiempirical, density functional and perturbation theoretical methods, the structure of the key intermediate is revealed and the metalloretentive nature of the mechanism is explained. The experimental ee values of a range of reactions with different electrophiles and carbonyl sources can be correlated with calculated differences in activation energies. Furthermore, it can be concluded that the selectivity derives from the internal stabilization of the transition state 3_syn (corresponding to an electrophilic attack from above the lithiohydrazone plane) by electrophile-lithium interactions. The fast computational approach can be used best as a screening method which excludes less promising candidates to guide this synthetic method.