Abstract: The kinetics of the reactions of benzhydryl cations with eight diazo compounds 1 a-g were investigated photometrically in dichloromethane. The nucleophilicity parameters N and slope parameters s of these diazo compounds were derived from the equation log k (20 degrees C)=s (E+N) and compared with the nucleophilicities of other pi systems (alkenes, arenes, silyl enol ethers, silyl ketene acetals). It is shown that the nucleophilic reactivities of diazo compounds cover more than ten orders of magnitude, being comparable to that of styrene on the low reactivity end and to that of enamines on the high reactivity end. The rate-determining step of these reactions is the electrophilic attack at the diazo-carbon atom to yield diazonium ions, which rapidly lose nitrogen.

Abstract: Molecular dynamics simulations with a combined quantum mechanical and molecular mechanical (QM/MM) potential have been carried out to investigate the squalene-to-hopene carbocation cyclization mechanism in squalene-hopene cyclase (SHC). The present study is based on free energy simulations by constructing the free energy surface for the cyclization steps along the reaction pathway. The picture that emerges for the carbocation cyclization cascade is a delicate balance of thermodynamic and kinetic control that ultimately favors the formation of the final hopanoids carbon skeleton. A key finding is that the five- to six-membered ring expansion process is not a viable reaction pathway for either C- or D-ring formation in the cyclization reaction. The only significant intermediate is the A/B-bicyclic cyclohexyl cation (III), from which two asynchronous concerted reaction pathways lead to, respectively, the 6,6,6,5-tetracyclic carbon skeleton and the 6,6,6,6,5-pentacyclic hopanoids. Experimentally, these two products are observed to have 1% and 99% yields, respectively, in the wild-type enzyme. We conclude that the product distribution in the wild-type enzyme is dictated by kinetic control of these two reaction pathways.

Abstract: A heterofullerene isoelectronic to C60 is reported. The azafullerenium cation C59N+ can be isolated in good yield as a carborane salt via the two-electron oxidation of the C−C bond of (C59N)2 dimer. [C59N][Ag(CB11H6Cl6)2] has been characterized by electronic, IR, Raman, and 13C NMR spectroscopies, MALDI spectrometry, DFT calculations, and X-ray crystallography.

Abstract: The Lewis acid treatment of 2,3-epoxysulfonates with 2,3-dialkyl substituents or 2-alkyl-3-aryl substituents produced the rearrangement products via C3-cleavage of the oxirane ring in high yields. On the other hand, 2-aryl-3-alkyl-2,3-epoxysulfonates produced the products via C2-cleavage of the oxirane ring. The sulfonyloxy groups of the α-sulfonyloxy ketones, having a chiral benzylic quaternary carbon center obtained by the rearrangement of 2-alkyl-3-aryl-2,3-epoxysulfonates, were reductively eliminated to give the ketones with a chiral benzylic quaternary carbon center. The method was applied to the formal synthesis of (−)-aphanorphine and total syntheses of (−)-α-herbertenol and (−)-herbertenediol.

Abstract: Stable chemical analogues of enzymatic transition states are imperfect mimics since they lack the partial bond character of the transition state. We synthesized structural variants of the Immucillins as transition state analogues for purine nucleoside phosphorylase and characterized them with the enzyme from Mycobacterium tuberculosis (MtPNP). PNPs form transition states with ribooxacarbenium ion character and catalyze nucleophilic displacement reactions by migration of the cationic ribooxacarbenium carbon between the enzymatically immobilized purine and phosphate nucleophiles. As bond-breaking progresses, carbocation character builds on the ribosyl group, the distance between the purine and the carbocation increases, and the distance between carbocation and phosphate anion decreases. Transition state analogues were produced with carbocation character and increased distance between the ribooxacarbenium ion and the purine mimics by incorporating a methylene bridge between these groups. Immucillin-H (ImmH), DADMe-ImmH, and DADMe-ImmG mimic the transition state of MtPNP and are slow-onset, tight-binding inhibitors of MtPNP with equilibrium dissociation constants of 650, 42, and 24 pM. Crystal structures of MtPNP complexes with ImmH and DADMe-ImmH reveal an ion-pair between the inhibitor cation and the nucleophilic phosphoryl anion. The stronger ion-pair (2.7 A) is found with DADMe-ImmH. The position of bound ImmH resembles the substrate side of the transition state barrier, and DADMe-ImmH more closely resembles the product side of the barrier. The ability to probe both substrate and product sides of the transition state barrier provides expanded opportunities to explore transition state analogue design in N-ribosyltransferases. This approach has resulted in the highest affinity transition state analogues known for MtPNP.

Abstract: The interaction of benzo(a)pyrene (BP) and its metabolites with the G–C base pair has been studied using the self-consistent-charge, density functional tight-binding(SCC-DFTB-D) method, augmented by the empirical London dispersion energy term. Structures of the complexes corresponding to a minimum interaction energy obtained using a constrained rigid body search were fully optimized. It is found that the benzylic ring of BP and its anti-conformers is located below the NH2 group of guanine while the syn-conformers exhibit a different binding pattern. The BP triol carbocation (BPTC) in the anti-conformation is stabilized by an additional hydrogen bond between the hydrogen atom of the OH group of BPTC and the N3 atom of guanine of the G–C base pair. The benzylic ring of BPTC directed toward the minor groove side whereas the pyrenyl ring stacks below the cytosine covering the hydrogen bond region. Guanine bends toward the benzylic ring, making an angle of ∼11–15° with the pyrene ring. The calculated equilibrium structures are in good agreement with the available experimental and other theoretical results. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 95: 44–59, 2003

Abstract: We have synthesized all three possible isomers of C-hydroxycarborane from the corresponding amines via diazotization. The O-protonated C-hydroxycarboranes were characterized using the NMR spectrum measurements. Attempts at generating of carboranyl carbocations were carried out by the solvolyses of C-tosylates and C-triflates, as well as by treatment with superacids. Anchimeric assistance of both homoconjugative and hyperconjugative substituents was also investigated, as demonstrated by a successful strategy devised for the solvolytic generation of a phenyl cation. However, we have not been able to chemically provide any evidence of carboranyl carbocations, although the carboranyl carbocation may be an intermediate in the decomposition of the C-carboranediazonium ion.

Abstract: A heterofullerene isoelectronic to C60 is reported. The azafullerenium cation C59N+ can be isolated in good yield as a carborane salt via the two-electron oxidation of the C−C bond of (C59N)2 dimer. [C59N][Ag(CB11H6Cl6)2] has been characterized by electronic, IR, Raman, and 13C NMR spectroscopies, MALDI spectrometry, DFT calculations, and X-ray crystallography.

Abstract: Protonation of parent azulene (1), homoazulene (8), representative isomeric benzazulenes (9, 9A, and 9B), and benzohomoazulenes (10, 10A, and 10B) as well as the mono- and diprotonation of isomeric azulenoazulenes (11–16) were studied by DFT at the B3LYP/6-31G(d) level. The most likely carbocations were identified based on relative protonation energies. For comparison, complete experimental 13C NMR data were obtained for parent azulenium ion 1H+++++ and guaiazulenium ion 2H++++ in TFA. The oxidation dications derived from benzazulenes (9, 9A, and 9B), benzohomoazulenes (10, 10A, and 10B) and azulenoazulenes (11–16) were also investigated. For azulenoazulene dications the singlet and triplet states are both minima, but except for 112+2+2+ and 132+, the triplet states are higher in energy. Structural/geometrical changes in the carbocations were examined. GIAO-NMR, NPA charges (and changes in charges), and NICS (and ΔNICS) were employed to compute the NMR chemical shifts (Δδ13C values) in order to derive charge delocalization maps and to gauge relative aromaticity/antiaromaticity in the energetically most favored carbocations and oxidation dications. The emerging trends are discussed and compared. Creation of tropylium or homotropylium entities in the carbocations (monoprotonated) and carbodications (diprotonated) is identified as an important driving force governing the protonation outcomes. Consideration of the AM1-derived ΔΔHf values (and the DFT-derived ΔΔG values) suggests that the two-electron oxidation of azulenoazulenes should be experimentally feasible. Given their antiaromatic (paratropic) character, azulenoazulene dications represent interesting targets for NMR study. GIAO-derived charge delocalization mapping allows the most likely sites for nucleophilic attack on the dications to be identified.

Abstract: N-tert-Butylimidozirconocene (Cp2ZrNt-Bu) and its analogue (ebthi)ZrNAr (ebthi = ethylenebis(tetrahydroindenyl), Ar = 2,6-dimethylphenyl) undergo overall cycloaddition reactions at ambient temperature with epoxides that lack accessible β-hydrogens. The process results in addition of the ZrN bond to an epoxide CO bond, leading to azazirconacyclopentanes. The regio- and stereochemistry of the products implicate a stepwise mechanism, with the intermediacy of zwitterions having substantial carbocation character at the substituted carbon of the ring-opened epoxide-derived fragment. The azametallacycles undergo facile cleavage to β-amino alcohols upon addition of mild acid.

Abstract: Mesylate derivatives of 3-aryl-3-hydroxy-β-lactams and thiolactams react in DMSO-d6 by first-order processes to give alcohol products. Substituent effect studies implicate carbocation intermediates (ion-pairs) that are captured by DMSO-d6 to give transient oxosulfonium ions. Rapid reaction of the oxosulfonium ions with trace amounts of water leads to the alcohol product and regenerates DMSO-d6. H217O labeling studies show that 17O is incorporated into the DMSO. The mesylate derivatives of endo- and exo-2-hydroxy-2-phenylbicyclo[2.2.1]heptan-3-one also react in DMSO-d6 to give the alcohol products. Ion-pair intermediates that capture DMSO giving unstable oxosulfonium ions are again proposed. Exo-2-phenyl-endo-bicyclo[2.2.1]heptyl trifluoroacetate readily eliminates trifluoroacetic acid in DMSO-d6 via a cationic mechanism involving loss of the endo-trifluoroacetate leaving group as well as an exo-hydrogen. The O-methyl oxime derivative of α-chloro-α,α-diphenylacetophenone reacts in DMSO-d6 to give 1-methoxy...

Abstract: Herein we describe our search for a carbocation with a delocalized 5-center 4-electron C- - -H- - -C- - -H- - -C bonding array. Various helical and polycyclic molecular architectures were explored using B3LYP calculations, ultimately leading to cation 8, a remarkable species that possesses two trigonal pyramidal carbons flanking a five-coordinate trigonal bipyramidal carbon.

Abstract: The influence of nonbonded interactions in the kinetics of formation of chalcogenol (thiol and selenol) esters from chalcogenoacetylenes was studied by molecular modeling. Using semiempirical and density functional theory methods it was possible to explain the differences between the reaction rates for the analogous sulfur and selenium chalcogenoacetylenes as well as evaluate the structural and electronic effects (nonbonded interactions) on the formation of the esters. The differences in the reaction rates can be explained in terms of the carbocation stabilization by the chalcogen atom. It is proposed that these differences are due to the differences in the intensity of the dominant interaction π/nY between the nonbonding orbitals of sulfur and selenium with the vacant orbital of carbon in the cationic transition state. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 95: 267–273, 2003

Abstract: The irradiation of N,N-dimethyl-4-chloroaniline in the presence of open-chain dienes in acetonitrile leads to addition of the aminophenyl and chloro groups across one of the double bonds; transannular cyclization takes place with cyclic dienes, leading to an arylnortricyclene from norbornadiene and to 1-arylbicyclo[3.3.0]octanes from 1,5-cyclooctadiene. The reaction proceeds by photoheterolysis of the chloroaniline to yield the 4-aminophenyl cation and addition to a C=C double bond. The chemistry of the adduct cation depends on structure and medium, involving ion pairs in MeCN and solvated ions in CF 3 CH 2 OH. In the latter solvent, formation of ethers from open-chain alkenes is accompanied by Wagner-Meerwein hydride shift. In acetonitrile, the cation from cyclooctadiene partitions between deprotonation and Ritter addition, while the one from norbornadiene is reduced; both cations undergo nucleophilic addition in trifluoroethanol. The relevance of these cationic reactions under unusually mild conditions is discussed.

Abstract: Nickel carbene complex 2 [Ni(triphos)C(H)N(H)xylyl]2+(BF4-)2 reacts with alkenes quantitatively and regiospecifically to give the anti-Markovnikov hydrocarbation products. X-ray crystallography shows significant iminium alkyl character of the hydrocarbation products, similar to that observed in parent carbene 2. Mechanistic studies suggest the importance of a "hydride" pathway over "alkene" (metallocycle formation or carbocation) pathways.

Abstract: Rate constant ratios for addition of the three nucleophilic sites of phenol to the 1-(4-methoxyphenyl)ethyl carbocation (1 + ) in 50/50 (v/v) trifluoroethanol/water were determined from the relative yields of the three phenol adducts, and absolute rate constants were determined from product rate constant ratios for addition of phenol and azide ion to 1 + using k az = 5 × 10 9 M -1 s -1 for the diffusion-limited reaction of azide ion. A selectivity of 230:20:1 was determined for alkylation of phenol at oxygen, C-4 and C-2 to form 1-OPh and biphenyls 1-(4-C 6 H 4 OH) and 1-(2-C 6 H 4 OH), respectively, and of 2:2:1 for alkylation of the corresponding nucleophilic sites of phenoxide ion in diffusion-limited reactions. The Mayr nucleophilicity parameter for C-4 of phenol is N= 2.0. Encounter-limited addition of phenoxide ion to 1 + to form 1-OPh is faster than encounter-limited addition of oxygen anions that are either more or less basic than phenoxide ion. Only the products of solvolysis are observed from acid-catalyzed cleavage of 1-OPh in 50/50 (v/v) trifluoroethanol/water, but a 50% yield of biphenyls 1-(4-C 6 H 4 OH) and 1-(2-C 6 H 4 OH) are observed from spontaneous cleavage of 1-OPh, where the leaving group is phenoxide ion, because of the very low kinetic barriers to collapse of the ion pair intermediate 1 + PhO - . The 230-fold larger rate constant for O-compared to C-2-alkylation of phenol is due primarily to the larger thermodynamic driving force for oxygen addition. There are similar Marcus intrinsic barriers for these two reactions.

Abstract: We examined the effect ofp-substituents inp-substituted cinnamyl methyl ethers and 1-(p-substituted phenyl)allyl methyl ethers with CSI, and confirmed that the CSI reaction of allyl ethers (p-substituted ethers) is a competitive reaction of SN j and SN1 mechanism according to the stability of the carbocation. And, the only terminal allylic amine was obtained through the migration reaction in thermodynamic reaction condition.

Abstract: A stable ion study of a series of BaP derivatives is reported. 7,8-Dihydro-BaP 1 gives a persistent bay-region benzylic-like carbocation which shows extensive charge delocalization into the pyrene moiety. In contrast, a “benzylic” carbocation can not be generated from 9,10-dihydro-BaP 2. Introduction of bulky substituents at peri C-6 of 9,10-dihydro-BaP (as in 4 and 5) prevents side reactions (dimerization) to the extent that the initially formed carbocation undergoes rearrangement to generate the corresponding bay-region “benzylic” carbocation as a persistent species. Introduction of methoxy substituents into the 1- or 3- positions of 9,10-dihydro-BaP-7(8H)-one (6,7) increases its electrophilic reactivity to the extent that stable carboxonium–arenium dications are produced in FSO3H–SO2ClF. A detailed NMR study (at 500 MHz) of the resulting mono- and dications is reported, and charge delocalization mode (as well as conformational aspects) are addressed. Other oxidized derivatives of BaP such as the 7,8-dihydrodiol 9 and the 7,8-dihydrodibenzoate 8 are not suitable models for stable ion study because of competing O-protonation (and elimination). Energies for various possible arenium ions and regioisomeric “benzylic” cations were computed by the DFT method at the B3LYP/6-31G(d)//B3LYP/6-31G(d) level or by AM1 for comparison with the experimental results. These findings provide further evidence in support of the stability sequence: 1-pyrenyl > 4-pyrenyl > 2-pyrenyl in α-pyrene-substituted carbocations as models for the intermediates arising from BaP-epoxide ring opening. In an effort to provide a parallel, a series of α-pyrenylcarbinols were subjected to a DNA binding study using human MCF-7 cells. The results/trends are discussed and compared with the stable ion data.

Abstract: Three plausible routes for the five-membered ring expansion in the equilibrating 2-cyclopentyl-2-propyl and 1-(2-propyl)cyclopentyl cations 1A/1B were located on the PES, all calculated at the MP4/6-31G(d)//MP2/6-31G(d) level of theory. In pathway I, the six-membered transition structure (TS-I) connects the less stable cyclopentyl cation 1A and the 1, 2-dimethylcyclohexyl carbocation (2) via a barrier of 16.4 kcal/mol. In pathway 11, which has a barrier of 16.3 kcal/mol, the methyl migration occurs first in the more stable 113 via transition structure TS-II. Pathway III involves the uphill hydride shift and formation of the secondary cation 3, which undergoes Wagner-Meerwein 1, 2-isopropyl shift via a transition structure TS-III and the protonated carbocation intermediate 4. The barrier pathway III is for 17.0 kcal/mol. Experimental secondary deuterium isotope effects of the rearrangement were measured for the hexadeuterated 1A-d(6)/1B-d(6) (k(H)/k(D) = 2.40) and tetradeuterated 1A-d(4)/1B-d(4) (k(H)/k(D) = 0.18) cations by means of H-1 NMR. Comparison of the experimental data with the theoretical values (k(H)/k(D) = 2.40 for 1B-d(6) and k(H)/k(D) = 0.24 for 1B-d(4), respectively) obtained with QUIVER revealed that pathway II is a major reaction route.

Abstract: We prepared thin molecular films of ethanol and 2-methylpropan-2-ol on Ru(001) substrates at temperature of 100-150 K and examined their reactivity toward HBr. The reaction intermediates and products formed at the surfaces were unambiguously identified by the techniques of Cs(+) reactive ion scattering (RIS) and low-energy sputtering. The reaction on the ethanol surface produced protonated ethanol, which is stabilized on the surface and does not proceed to further reactions. On the 2-methylpropan-2-ol surface, protonated alcohol [(CH(3))(3)COH(2) (+)] and carbocation [(CH(3))(3)C(+)] were formed with the respective yield of 20 and 78 %. Alkyl bromides, which are the final products of the corresponding reactions in liquid solvents, have extremely small yields on these surfaces (< 0.3 % for ethyl bromide and 2 % for tert-butyl bromide). The results indicate that the reactions on frozen films are characterized by kinetic control, stabilization of ionic intermediates (protonated alcohols and tert-butyl cation), and effective blocking of the charge recombination steps in S(N)1 and S(N)2 paths. The implication of these findings for the molecular evolution process in interstellar medium is also discussed.