Theoretical study on the isomerization behavior between alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals

[reaction: see text] Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ, and a (valence) double-zeta pseudopotential (DZP) basis set, with (QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional methods (BHandHLYP, B3LYP) predict that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals exist as isomers. At the CCSD(T)/cc-pVDZ//BHandHLY/cc-pVDZ level of theory, energy barriers of 15.1 and 17.7-21.7 kJ mol(-)(1) are calculated for the isomerization of s-trans-propenoyl and s-trans-crotonoyl radical to ketenylmethyl and 1-ketenylethyl radical, respectively. Similar results are obtained for the reactions of s-trans isomers involving silyl, germyl, and stannyl groups with energy barriers (DeltaE++) of 12.2-12.4, 13.1-13.9, and 12.9-18.2 kJ mol(-)(1) at the CCSD(T)/DZP//BHandHLYP/DZP calculation, respectively. These results suggest that alpha,beta-unsaturated acyl radicals and alpha-ketenyl radicals are not canonical forms but are isomeric species that can rapidly interconvert.     

An ab-initio study of some homolytic substitution reactions of acyl radicals at silicon, germanium and tint

Ab initio calculations using the 6-311G**, cc-pVDZ, and (valence) double-zeta pseudopotential (DZP) basis sets, with (MP2, QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional (BHandHLYP, B3LYP) calculations predict that homolytic substitution reactions of acetyl radicals at the silicon atoms in disilane can proceed via both backside and frontside attack mechanisms. At the highest level of theory (CCSD(T)/cc-pVDZ//MP2/cc-pVDZ), energy barriers (deltaE double dagger) of 77.2 and 81.9 kJ mol(-1) are calculated for the backside and frontside reactions respectively. Similar results are obtained for reactions involving germanium and tin with energy barriers (deltaE double dagger) of 53.7-84.2, and 55.0-89.7 kJ mol(-1) for the backside and frontside mechanisms, respectively. These data suggest that both homolytic substitution mechanisms are feasible for homolytic substitution reactions of acetyl radicals at silicon, germanium, and tin. BHandHLYP calculations provide geometries and energy barriers for backside and frontside transition states in good agreement with those obtained by traditional ab initio techniques.     

Multiorbital interactions during Acyl radical addition reactions involving imines and electron-rich olefins

Ab initio and DFT calculations reveal that acyl radicals add to imines and electron-rich olefins through simultaneous SOMO --> pi*, pi --> SOMO, and HOMO --> pi*C=O interactions between the radical and the radicalophile. At the CCSD(T)/aug-cc-pVDZ//QCISD/cc-pVDZ level, energy barriers of 15.6 and 17.9 kJ mol(-1) are calculated for the attack of the acetyl radical at the carbon and nitrogen ends of methanimine, respectively. These barriers are 17.1 and 20.4 kJ mol(-1) at BHandHLYP/cc-pVDZ. In comparison, barriers of 34.0 and 23.4 kJ mol(-1) are calculated at BHandHLYP/cc-pVDZ for reaction of the acetyl radical at the 1- and 2-positions in aminoethylene, repectively. Natural bond orbital (NBO) analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO --> pi*imine, pi imine--> SOMO, and LPN --> pi*C=O interactions are worth 90, 278, and 138 kJ mol-1, respectively, in the transition state (2) for reaction of acetyl radical at the nitrogen end of methanimine; similar interactions are observed for the chemistry involving aminoethylene. These multiorbital interactions are responsible for the unusual motion vectors associated with the transition states involved in these reactions. NBO analyses for the remaining systems in this study support the hypothesis that the acetyl radical is ambiphilic in nature.     

Multi-component orbital interactions during oxyacyl radical addition reactions involving imines and electron-rich olefins

Ab initio and DFT calculations reveal that oxyacyl radicals add to imines and electron-rich olefins through simultaneous SOMO-pi*, SOMO-pi and pi*-HOMO interactions between the radical and the radicalophile. At the BHandHLYP/aug-cc-pVDZ level, energy barriers of 20.3 and 22.0 kJ mol(-1) are calculated for the attack of methoxycarbonyl radical at the carbon and nitrogen ends of methanimine, respectively. In comparison, barriers of 22.0 and 8.6 kJ mol(-1) are calculated at BHandHLYP/aug-cc-pVDZ for reaction of methoxycarbonyl radical at the 1- and 2-positions in aminoethylene, respectively. Natural bond orbital (NBO) analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO-pi*, SOMO-pi and pi*-LP interactions are worth 111, 394 and 55 kJ mol(-1) respectively in the transition state (8) for reaction of oxyacyl radical at the nitrogen end of methanimine; similar interactions are observed for the chemistry involving aminoethylene. These multi-component interactions are responsible for the unusual motion vectors associated with the transition states involved in these reactions.     

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.     

Intramolecular homolytic substitution of sulfinates and sulfinamides--a computational study

Ab initio and density functional theory (DFT) calculations predict that intramolecular homolytic substitution by alkyl radicals at the sulfur atom in sulfinates proceeds through a smooth transition state in which the attacking and leaving radicals adopt a near collinear arrangement. When forming a five-membered ring and the leaving radical is methyl, G3(MP2)-RAD//ROBHandHLYP/6-311++G(d,p) calculations predict that this reaction proceeds with an activation energy (ΔE(1)(?)) of 43.2 kJ mol(-1). ROBHandHLYP/6-311++G(d,p) calculations suggest that the formation of five-membered rings through intramolecular homolytic substitution by aryl radicals at the sulfur atom in sulfinates and sulfinamides, with expulsion of phenyl radicals, proceeds with the involvement of hypervalent intermediates. These intermediates further dissociate to the observed products, with overall energy barriers of 45-68 kJ mol(-1), depending on the system of interest. In each case, homolytic addition to the phenyl group competes with substitution, with calculated barriers of 51-78 kJ mol(-1). This computational study complements and provides insight into previous experimental observations.     

Methyl radical also reacts by the frontside mechanism: an ab initio study of some homolytic substitution reactions of methyl radical at silicon,germanium and tin

Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ, and a (valence) double-zeta pseudopotential (DZP) basis sets, with (MP2, QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional (B3LYO) calculations predict that homolytic substitution reactions of the methyl radical at the silicon atom in disilane can proceed via both backside and frontside attack mechanisms. At the highest level of theory (CCSD(T)/aug-cc-pVDZ//MP2/aug-cc-pVDZ), energy barriers (delta E) of 47.4 and 48.6 kJ mol-1 are calculated for the backside and frontside reactions respectively. Similar results are obtained for reactions involving germanium and tin with energy barriers (delta E) of between 46.5 and 67.3, and 41.0 and 73.3 kJ mol-1 for the backside and frontside mechanisms, respectively. These data suggest that homolytic substitution reactions of methyl radical at silicon, germanium, and tin can proceed via either homolytic substitution mechanism.     

Cu‐Catalyzed Hydroxymethylation of Unactivated Alkyl Iodides with CO To Provide One‐Carbon‐Extended Alcohols

We have developed a reductive carbonylation method by which unactivated alkyl iodides can be hydroxymethylated to provide one‐carbon‐extended alcohol products under Cu‐catalyzed conditions. The method is tolerant of alkyl β‐hydrogen atoms, is robust towards a wide variety of functional groups, and was applied to primary, secondary, and tertiary alkyl iodide substrates. Mechanistic experiments indicate that the transformation proceeds by atom‐transfer carbonylation (ATC) of the alkyl iodide followed in tandem by two CuH‐mediated reductions in rapid succession. This radical mechanism renders the Cu‐catalyzed system complementary to precious‐metal‐catalyzed reductive carbonylation reactions.     

Intramolecular carbozincation of unactivated alkenes occurs through a zinc radical transfer mechanism

The cyclizations of a number of terminally unsaturated alkenyl zinc iodides to cyclopentylmethylzinc iodides, formerly believed to be nonradical in nature, have been revealed as radical chain cyclizations initiated by adventitious oxygen. Five cases are presented in which the published carbozincation cis/trans selectivities are essentially the same as those found for the cyclizations of the unsaturated alkyl iodide precursors of the alkylzinc iodides by the iodine atom transfer method at approximately the same temperatures. In addition, it has been found that one of the organozinc cyclizations does not occur in a system in which oxygen has been rigorously excluded. The combined findings strongly suggest that these organozinc cyclizations occur by a zinc radical transfer mechanism rather than by a conventional carbometallation that is thought to occur with the analogous organolithium and organomagnesium cyclizations.     

An ab initio and DFT study of radical addition reactions of imidoyl and thioyl radicals to methanimine

Ab initio and DFT calculations reveal that both imidoyl and thioyl radicals add to the nitrogen end of methanimine through simultaneous SOMO-π*(imine), SOMO-π(imine), SOMO-LP(N) and π*(radical)-LP(N) interactions between the radical and the imine. At the CCSD(T)/cc-pVDZ//BHandHLYP/cc-pVTZ level of theory, barriers of 13.8 and 26.1 kJ mol(-1) are calculated for the attack of the methylimidoyl radical at the carbon- and nitrogen- end of methanimine, respectively, indicating that the imidoyl radial has a preference for addition to the nitrogen end of imine. On the other hand, barriers of 25.1 and 13.4 kJ mol(-1) are calculated at the same level of theory for the addition reaction of the methanethioyl radical at the carbon- and nitrogen- end of methanimine, respectively. Natural bond orbital (NBO) analysis at the BHandHLYP/6-311G** level of theory reveals that SOMO-π*(imine), SOMO-π(imine), SOMO-LP(N) and π*(radical)-LP(N) interactions are worth 111, 89, 115 and 17 kJ mol(-1), respectively, in the transition state (4) for the reaction of methylimidoyl radical at the nitrogen end of methanimine; similar interactions are observed for the chemistry involving all the radicals studied here. These multi-component interactions are responsible for the unusual motion vectors associated with the transition states involved in these reactions.     

Intramolecular hydrogen bonding and hydrogen atom abstraction in gas-phase aliphatic amine radical cations

The intramolecular hydrogen atom abstraction by the nitrogen atom in isolated aliphatic amine radical cations is examined experimentally and with composite high-level ab initio methods of the G3 family. The magnitude of the enthalpy barriers toward H-atom transfer varies with the shape and size of the cyclic transition state and with the degree of substitution at the nitrogen and carbon atoms involved. The lower barriers are found for 1,5- and 1,6-abstraction, for chairlike transition states, for abstraction reactions in ionized primary amines, and for abstraction of H from tertiary carbon atoms. In most cases, the internal energy required for 1,4-, 1,5-, and 1,6-hydrogen atom abstraction to occur is less than that required for gas-phase fragmentation by simple cleavage of C-C bonds, which explains why H-atom transfer can be reversible and result in extensive H/D exchange prior to the fragmentation of many low-energy deuterium labeled ionized amines. The H-atom transfer to nitrogen is exothermic for primary amine radical cations and endothermic for tertiary amines. It gives rise to a variety of distonic radical cations, and these may undergo further isomerization. The heat of formation of the gauche conformers of the gamma-, delta-, and epsilon-distonic isomers is up to 25 kJ mol(-1) lower than that of the corresponding trans forms, which is taken to reflect C-H-N hydrogen bonding between the protonated amino group and the alkyl radical site.     

Abstraction of iodine from aromatic iodides by alkyl radicals: steric and electronic effects

Abstraction of the iodine atom from aryl iodides by alkyl radicals takes place in some cases very efficiently despite the unfavorable difference in bond dissociation energies of C-I bonds in alkyl and aryl iodides. The abstraction is most efficient in iodobenzenes, ortho-substituted with bulky groups. The ease of abstraction can be explained by the release of steric strain during the elimination of the iodine atom. The rate of abstraction correlates fairly well with the strain energy, calculated by density functional theory (DFT) and Hartree-Fock (HF) methods as a difference in the total energy of ortho and para isomers. However, besides the steric bulk, the presence of some other functional groups in an ortho substituent also influences the rate. The stabilization of the transition state, resembling a 9-I-2 iodanyl radical, by electron-withdrawing groups seems to explain a positive sign of the Hammett rho value in the radical abstraction of halogen atoms.     

Aryl Radical‐Mediated Alkenylation of Alkyl Halides

The free‐radical alkenylation of a range of alkyl iodides with a vinyldisulfones has been carried out, leading to the desired vinylsulfones in moderate to good yields under mild conditions. The process is initiated by an aryl radical which abstracts the iodine atom from the alkyl iodide to form a C‐centered radical intermediate, the addition of which onto the vinyldisulfone providing the final vinylsulfone. The aryl radical is generated in situ through a single‐electron transfer from an electron donor‐acceptor complex (EDA) formed between a diaryliodonium salt (Ph₂I⁺ PF₆^?) and triethylamine.     

Palladium-catalyzed cycloisomerizations of (Z)-1-iodo-1,6-dienes: iodine atom transfer and mechanistic insight to alkyl iodide reductive elimination

A palladium-catalyzed iodine atom transfer cycloisomerization of (Z)-1-iodo-1,6-diene has been developed, which provides a facile method to construct six-memebered heterocycles bearing an alkyl iodide group. The ligand screening shows that both the type and the quantity of ligand impose significant influences on this transformation, and the combination of 30 mol % 1,1'-bis(diphenylphosphino)ferrocene (DPPF) and 10 mol % Pd(OAc)(2) is the optimal choice. The catalytic cycle, consisting of oxidative addition of Pd(0) to vinyl iodide, intramolecular alkene insertion, and alkyl iodide reductive elimination, has been proposed and eventually supported by convincing evidence from a series of control experiments. More importantly, these control experiments disclose some features of the event of alkyl iodide reductive elimination: (1) this reductive elimination is proved to be a stereospecific process; and (2) both alkyl iodide oxidative addition and reductive elimination are not effected by a TEMPO additive. Besides its ability to undergo oxidative addition, the catalyst (palladium + DPPF) could also promote a radical transfer process. The findings described in this paper will be helpful for further development of the metal-catalyzed formation of a carbon-halide bond.     

Density functional theory studies of negishi alkyl-alkyl cross-coupling reactions catalyzed by a methylterpyridyl-Ni(I) complex

Density functional theory calculations were done to examine the potential energy surfaces of Ni(I)-catalyzed Negishi alkyl-alkyl cross-coupling reactions by using propyl iodide and isopropyl iodide as model alkyl electrophiles and CH 3ZnI as a model alkyl nucleophile. A four-step catalytic cycle involving iodine transfer, radical addition, reductive elimination, and transmetalation steps were characterized structurally and energetically. The reaction mechanism for this catalytic cycle appears feasible based on the calculated free energy profiles for the reactions. The iodine transfer step is the rate-determining step for the Ni(tpy)-CH 3 (tpy = 2,2'6',2'-terpyridine) reactions with alkyl iodides. For secondary alkyl electrophiles, the oxidative addition intermediate, Ni(III), prefers to undergo decomposition over reductive elimination, whereas for the primary alkyl electrophiles, Ni(III) prefers to undergo reductive elimination over decomposition based on comparison of the relative reaction rates for these two types of steps. In addition, thermodynamic data were employed to help explain why the yield of the coupled product is very low from the Ni(II)-alkyl halide reactions with organozinc reagents.     

Intramolecular homolytic translocation chemistry: an ab initio study of 1,n-silyl, germyl, and stannyl group transfer and related ring-closure reactions

Ab initio calculations using 6-311G**, cc-pVDZ, aug-cc-pVDZ, and a (valence) double-zeta pseudopotential (DZP) basis set, with (MP2, QCISD, CCSD(T)) and without (UHF) the inclusion of electron correlation, and density functional methods (B3LYP) predict that 1,n-homolytic transfers (n = 1-5) of silyl, germyl, and stannyl groups from group IV heteroatoms to carbon radicals can proceed via a frontside attack mechanism. At the B3LYP/DZP level of theory, energy barriers (DeltaE++) of 101.2, 98.8, 58.9, and 63.4 kJ/mol are calculated for the 1,2-, 1,3-, 1,4-, and 1,5-translocation reactions, respectively, of SiH3 between silicon atoms. Similar results are obtained for reactions involving germanium and tin with energy barriers (DeltaE++) of 85.9-113.1, 84.4-109.0, 41.7-73.3, and 48.5-78.2 kJ/mol for the 1,2-, 1,3-, 1,4-, and 1,5-translocation reactions, respectively. This study also predicts that four- and five-membered ring-closure reactions can be competitive with the 1,4- and 1,5-translocation reactions. These results suggest that while 1,2- and 1,3-translocation four-membered ring-formation reactions are unlikely to be synthetically viable, 1,4- and 1,5-transfers and five-membered ring-formation have synthetic possibilities.     

A quantum chemical study of the protonation of phenylphosphine and its halogenated derivatives

The protonation and methylation of phenylphosphine (C(6)H(5)PH(2)) and its mono-halogenated derivatives have been studied using ab initio quantum chemical calculations. Density functional theory (B3LYP) calculations using the 6-311++G(d,p) basis set consistently confirm that protonation of phenylphosphines takes place at the phosphorus atom; the C(4)-protonated phenylphosphine lying about 66 kJ mol(-1) above the P-protonated isomer. Similarly, methylation of phosphines consistently occurs at phosphorus. The proton and methyl cation affinities are estimated as follows: PA(phenylphosphine) = 863 +/- 10 kJ mol(-1) and MCA(phenylphosphine) = 515 -/+ 12 kJ mol(-1). Mono-halogen substitution appears to reduce the proton affinites by up to 20 kJ mol(-1). In this context, following P-protonation of either ameta- or a para-X-C(6)H(4)-PH(2), an elimination of the halogen X-atom under collisional activation (CA) conditions is expected to lead to a distonic radical cation, a low-energy isomer being 50 kJ mol(-1) above ionized phenylphosphine.     

S-to-αC Radical Migration in the Radical Cations of Gly-Cys and Cys-Gly

The radical cations of Cys-Gly and Gly-Cys were studied using ion-molecule reactions (IMR), infrared multiple-photon dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations. Homolytic cleavage of the S–NO bond of nitrosylated precursors generated radical cations with the radical site initially located on the sulfur atom. Time-resolved ion-molecule reactions showed that radical site migration via hydrogen atom transfer (HAT) occurred much more quickly in Gly-Cys^•+ than in Cys-Gly^•+. IRMPD and DFT calculations indicated that for Gly-Cys, the radical migrated from the sulfur atom to the α-carbon of glycine, which is lower in energy than the sulfur radical (–53.5 kJ/mol). This migration does not occur for Cys-Gly because the glycine α-carbon is higher in energy than the sulfur radical (10.3 kJ/mol). DFT calculations showed that the highest energy barriers for rearrangement are 68.2 kJ/mol for Gly-Cys and 133.8 kJ/mol for Cys-Gly, which is in agreement with both the IMR and IRMPD data and explains the HAT in Gly-Cys.     

N-nitrosation of amines by NO2 and NO: a theoretical study

Gas-phase nitrosation of amines implies a nonionic pathway different from the nitrosonium nitrosation via acidification of nitrite. Electronic structure calculations discussed in this work suggest a free radical mechanism, in which NO2 abstracts a hydrogen atom from the nitrogen in primary and secondary amines to form an intermediate complex of an aminyl radical and nitrous acid. The aminyl radical intermediate is then quenched by nitric oxide, leading to the formation of nitrosamine. High-level calculations (CBS-QB3) show that alkyl substitutions on amines can activate the H-abstraction reaction. Thus, while H-abstraction from NH3 was found to exhibit a reaction barrier (DeltaH) of 106 kJ/mol, similar calculations indicate that the corresponding barriers decrease to 72 and 45 kJ/mol for methylamine and dimethylamine, respectively. Heterocyclic secondary amines have also been investigated in a similar manner. The five-membered-ring (5-m-r) amine appears to be the most reactive: pyrrolidine (DeltaH=30 kJ/mol), azetidine (DeltaH=44 kJ/mol), piperidine (DeltaH=44 kJ/mol), and aziridine (DeltaH=74 kJ/mol). The reaction barrier for 1H-pyrrole, an aromatic 5-m-r secondary amine, was found to be 59 kJ/mol. The origin of the high activity for the 5-m-r alkylamine stems from a hydrogen-bond-like interaction between the aminyl radical and the nascent nitrous acid molecule. This theoretical study suggests that, in the presence of nitrogen oxides, the gas-phase nitrosation of secondary amines is feasible.     

Acyl iodides in organic synthesis: IX. Cleavage of the Si-O-C and Si-O-Si moieties

Reactions of acyl iodides RCOI (R = Me, Ph) with organosilicon compounds involve cleavage of the Si-O-C and Si-O-Si fragments. Acetyl iodide reacts with alkyl(alkoxy)silanes with evolution of heat, and cleavage of the Si-O bond results in the formation of oligo-or polysiloxanes, alkyl iodides, and alkyl acetates. 1,3-Diacetoxytetramethyldisiloxane is formed in the reaction of acetyl iodide with dimethoxy(dimethyl)silane. Acyl iodides readily react with 1-ethoxysilatrane to give 1-acyloxysilatranes as a result of cleavage of the C-O bond. The reaction of acetyl iodide with hexaethyldisiloxane yields triethylsilyl acetate and triethyliodosilane, while in the reaction with octamethyltrisiloxane iodo(trimethyl)silane and dimethyl(trimethylsiloxy)silyl acetate are obtained.