Initial Addition Step Research Articles

Accessing the Cloke-Wilson Rearrangement via Conjugate Addition of Phosphoranes to Michael Acceptors: A Route to Cyclopropanes and 5-Membered Ring Heterocycles Investigated by Density Functional and Ab Initio Theory.

Conjugate addition of unstabilized Wittig-type phosphonium ylides to 1,1-diacceptor- and 1-acceptor-substituted alkenes is investigated by density functional theory and high-level ab initio (DLPNO-CCSD(T)) calculations. The results indicate that the initial conjugate addition step should be facile with barriers predicted to be between 0 and 21 kcal mol-1. Potential intramolecular follow-up reactions include the formation of acceptor-substituted cyclopropanes as well as the formation of dihydrofuran derivatives via intramolecular SN2-type transition state structures. The barriers calculated for these potentially valuable cyclization reactions are substantial with Gibbs free energies of activation between 19 and 40 kcal mol-1. Competing reaction channels include Wittig olefination (for ketones and aldehydes), as well as Claisen condensation reactions. The reaction offers an alternative entry point to the nucleophile-catalyzed Cloke-Wilson rearrangement.

Selective Synthesis of Functionalized 3(2H)‐Furanones via Tandem Michael Addition/Rearrangement/Cyclization Reaction of Aliphatic Alkynones: A Combined Experimental and Theoretical Study

AbstractA novel catalyst‐ and solvent‐controlled dimerization of aliphatic alkynones through tandem Michael addition/rearrangement/cyclization sequence has been developed. The elaborated protocol provides a convenient chemo‐, regio‐ and stereoselective access to rare 3(2H)‐furanones decorated with 2‐exo‐methylene and 4‐ethenyl functionalities. A comprehensive density functional theory (DFT) study of possible reaction mechanism including ab initio molecular dynamics (AIMD) simulations and quantum theory of atoms in molecules (QTAIM) analysis of various substrate/catalyst/solvent complexes has revealed the Janus‐like behavior of the employed sodium tert‐butoxide/toluene system that is responsible both for the chemoselectivity of the initial addition step and the inhibition of the final cyclization step.

Theoretical Investigation on the Mechanistic Pathways of Cp*Cobalt(III)- Catalyzed Transformation of N-Substituted Carbamoyl Indoles to Pyrroloindolone Derivatives

Aim: A theoretical study on the Cp*cobalt(III) catalyzed C-H functionalization transformation of N-substituted carbamoyl indoles with alkyne derivatives to pyrroloindolone derivatives has been performed using DFT method. Background: Indole skeleton is an important part for developing regioselective C-H bond functionalisation reactions. Pyrrolo[1,2-a]indole bearing a 6-5-5 tricyclic skeleton (Scheme-1) is an important structural component found in many biologically active natural products and pharmaceuticals, (such as antitumor mitomycin C, antimalarial flinderole B etc.).Thus C−H activation process has great demand methods for efficiently synthesizing a pyrrolo[1,2-a]indole unit from readily available starting materials. One such attractive report was published by Matsunaga & Kanai et.al., Which shows pyrroloindolone derivatives can be synthesized (Scheme-2) through Cp*Co(III) catalysed C-H alkenylation and annulations from N-substituted carbamoyl indoles. Objective: Our current project deals with the determination of the rate determining step of the reaction, to determine the energetically favourable pathway. Investigation of the actual reason behind the regioselectivity of the products whether it is steric or electronic effects of the substituents. Method: The geometry optimization and energy calculations of all the systems were carried out with the Gaussian 09 software. Construction of trial geometries, monitoring the progress of calculations and visualization of the final output were done by several graphical user interface softwares like Gauss View, Molden etc. Geometry optimization of all species is performed using M06-2X functional in DFT method as a method for performing optimization of structures. 6-31G (d, p) basis set was employed for all non-metal atoms and the LANL2DZ basis set was employed for cobalt. To find out the geometries of several transition structures on the potential energy surface (PES) of the reaction pathway, relaxed scan method was used. Result: DFT study on a reaction of carbamoyl indoles with alkyne derivatives by activate Co(III)Cp* catalytic condition is done here. The target scheme followed the energetics of two possible pathways. The initial step of the reaction is the alkyne insertion step which needs 21.27 kcal mol-1 amount of energy. In the first case the final annulated product has been generated through a carbon-carbon bond formation, proton transfer and demetallation processes in path-a. The global activation barrier has been found to be quite high (30.17 kcal mol-1). However the study of the second pathway, which generated the simple alkenylated product through the proto-demetalation process in path-b, reveals a more reliable activation barrier (21.27 kcal mol-1). Conclusion: Comparison of the energy requirement clearly reveals that the formation of the final product should go through favourable simple alkenylation process that is path-b for dimethyl amine. Due to lower energy barrier the simple alkenylation pathway (i.e Path-b) is more favourable one. Initial alkyne addition step is the rate determining step. The regioselectivity of the alkyne addition is purely governed by the steric crowding around the substrate. Thus the favourable mode of alkyne addition has lower energy barrier due to lesser steric interactions. This theoretical investigation may guide the future researchers for developing some other economical route for generating similar derivatives.

Factors Controlling the Aluminum(I)-meta-Selective C-H Activation in Arenes.

The so far poorly understood factors controlling the complete meta‐selectivity observed in the C−H activation reactions of alkylarenes promoted by aluminyl anions have been explored in detail by means of Density Functional Theory calculations. To this end, a combination of state‐of‐the‐art computational methods, namely the activation strain model of reactivity and energy decomposition analysis, has been applied to quantitatively unveil the origin of the selectivity of the transformation as well as the influence of the associated potassium cation. It is found that the selectivity takes place during the initial nucleophilic addition step where the key LP(Al)→π*(C=C) molecular orbital interaction is more stabilizing for the meta‐pathway, which results in a stronger interaction between the reactants along the entire transformation.

Multireference Study of the H2COO (Criegee Intermediate) + O3 Addition: A Reaction of Possible Tropospheric Interest.

The addition of carbonyl oxides to ozone could have an effect on the tropospheric HO• nocturnal formation. Its mechanistic description has provided so far conflicting results. CASPT2 (and CASSCF) geometry optimizations, focused on the initial addition step, show that the most likely pathway is not a concerted cycloaddition to give directly a c-H2CO5 intermediate, as had been proposed. Concerted cycloaddition is in fact related to a second-order saddle point that puts in turn into relation, obliquely, two distinct diradicaloid transition structures. While O-O addition goes through an energy demanding pathway, C-O addition, potentially producing the open-chain •OOCH2-OOO• diradical intermediate, corresponds to a more viable pathway. CASPT2 and MRCI optimizations, though predicting an addition diradicaloid pathway, describe •OOCH2-OOO• as an unstable structure, because fragmentation to •OOCH2-O• + O2 takes place past the addition TS without any energy barrier: ring closure to c-H2CO5 is thus prevented. The addition E barrier drops as the methods become more demanding, with CASPT3//PT2 at 12.8 kcal mol-1, MRCI at 9.1 kcal mol-1, and MRCC at 4.8 kcal mol-1 (possibly suggesting a significant role of dynamical correlation). Recent experimental data by Chang et al. qualify this addition as a fairly fast reaction.

Selective Formation of Indene through the Reaction of Benzyl Radicals with Acetylene.

The combustion of fossil fuels forms polycyclic aromatic hydrocarbons (PAHs) composed of five- and six- membered aromatic rings, such as indene (C9 H8 ), which are carcinogenic, mutagenic, and deleterious to the environment. Indene, the simplest PAH with single five- and six-membered rings, has been predicted theoretically to be formed through the reaction of benzyl radicals with acetylene. Benzyl radicals are found in significant concentrations in combustion flames, owing to their highly stable aromatic and resonantly stabilized free-radical character. We provide compelling experimental evidence that indene is synthesized through the reaction of the benzyl radical (C7 H7 ) with acetylene (C2 H2 ) under combustion-like conditions at 600 K. The mechanism involves an initial addition step followed by cyclization and aromatization through atomic hydrogen loss. This reaction was found to form the indene isomer exclusively, which, in conjunction with the high concentrations of benzyl and acetylene in combustion environments, indicates that this pathway is the predominant route to synthesize the prototypical five- and six-membered PAH.

Rate coefficients and product branching ratios for the oxidation of phenyl and naphthyl radicals: A theoretical RRKM-ME study

Theoretical VRC-TST/RRKM-ME calculations were performed to evaluate total rate coefficients and product branching ratios for the oxidation of phenyl and 1- and 2-naphthyl radicals with O2 at temperatures relevant to combustion (1500, 2000, and 2500K) and pressures of 0.01, 0.1, 1.0, and 10atm. The results give the rate coefficients in the range of 3.0–5.5×10−11cm3 molecule−1s−1 with slightly positive temperature dependence, activation energies varying within 2.3–3.3kcal/mol, and pre-exponential factors of 7–10×10−11cm3 molecule−1s−1. The dominant reaction channel in all three cases is elimination of the oxygen atom from peroxy complexes formed at the initial O2 addition step and leading to the phenoxy and naphthoxy radical products. The contribution of this channel increases with temperature. Chemically-activated phenoxy and naphthoxy radicals either decompose to the cyclopentadienyl+CO and indenyl+CO products, respectively, or undergo thermal equilibration. The relative yields of the decomposition/equilibration products strongly depend on temperature and pressure in the way that a temperature growth favors decomposition, whereas an increase in pressure favors equilibration. At the lowest temperature considered, 1500K, the reactions also yield significant amounts of pyranyl+CO (phenyl+O2) or 1-benzopyranyl+CO (1-naphthyl+O2). A comparison of the phenyl+O2 and naphthyl+O2 reactions reveals that although the general trends in the oxidation kinetics of phenyl and naphthyl radicals are similar, the size and especially the position of the radical site in the aromatic moiety may affect the details of the mechanism and relative product yields.

Nucleophilic Substitution Reactions of 2‐Methoxy‐3‐X‐5‐nitrothiophenes: Effect of Substituents and Structure–Reactivity Correlations

ABSTRACTA kinetic study is reported for reactions of 2‐methoxy‐3‐X‐5‐nitrothiophenes 1a–d (X = SO2CH3, CO2CH3, CONH2, H) with piperidine in different solvents at 20°C. It is shown that the reactions take place through a SNAr mechanism with the initial nucleophilic addition step being rate limiting. The satisfactory Hammett correlations (log k1 vs. σ) obtained in the present system confirms that a 3‐X substituent exerts an effect on the 2‐position of the same type as that exerted from the 5‐position. The second‐order rate constants associated with these reactions are employed to determine the electrophilicity parameters E of the thiophenes 1a–d according to the relationship log k (20°C) = s(E + N) (Angew. Chem., Int. Ed. Engl. 1994, 33, 938–957). The E values of 1a–d are found to cover a range from −21.33 to −17.18, going from 1d, the least reactive, to 1a, the most reactive thiophene. Interestingly, a linear correlation (r2 = 0.9910) between the electrophilicity parameters E determined in this work and the Hammett's σ constants values has been observed and discussed. On the other hand, we have found that the reported rate constants of some thiophenes 1 complexation by the methoxide ion in methanol are 3.5–73.5 times higher than predicted by Mayr's approach.

How is acetylcholinesterase phosphonylated by soman? An ab initio QM/MM molecular dynamics study.

Acetylcholinesterase (AChE) is a crucial enzyme in the cholinergic nerve system that hydrolyzes acetylcholine (ACh) and terminates synaptic signals by reducing the effective concentration of ACh in the synaptic clefts. Organophosphate compounds irreversibly inhibit AChEs, leading to irreparable damage to nerve cells. By employing Born–Oppenheimer ab initio QM/MM molecular dynamics simulations with umbrella sampling, a state-of-the-art approach to simulate enzyme reactions, we have characterized the covalent inhibition mechanism between AChE and the nerve toxin soman and determined its free energy profile for the first time. Our results indicate that phosphonylation of the catalytic serine by soman employs an addition–elimination mechanism, which is highly associative and stepwise: in the initial addition step, which is also rate-limiting, His440 acts as a general base to facilitate the nucleophilic attack of Ser200 on the soman’s phosphorus atom to form a trigonal bipyrimidal pentacovalent intermediate; in the subsequent elimination step, Try121 of the catalytic gorge stabilizes the leaving fluorine atom prior to its dissociation from the active site. Together with our previous characterization of the aging mechanism of soman inhibited AChE, our simulations have revealed detailed molecular mechanistic insights into the damaging function of the nerve agent soman.

Pd‐Catalyzed Ring Assembly by Vinylation and Intramolecular Heck Coupling: A Versatile Strategy Towards Functionalized Azadibenzocyclooctynes

A new modular approach based on Pd-catalyzed C-C bond formation is presented for the assembly of a benzannulated azocine scaffold, the key intermediate in the synthesis of functionalized azadibenzocyclooctynes (aza-DIBOs). The intramolecular ring-closing Heck coupling was investigated by variation of the C-X bond. The reaction rate is limited by the initial oxidative addition step and the regiochemistry strongly depends on the auxiliary phosphine. Under optimized conditions, the 8-endo regioisomer was obtained in 71% yield over two steps (with no protecting group chemistry) or in one pot, inclusive of C-N bond formation. The practical generation of the octyne triple bond of a prototypical N-benzoyl aza-DIBO, without the need for chromatographic purification, is also described. The structural features, including those of the ring-strained cyclic octyne, were elucidated by NMR spectroscopy and X-ray crystallographic analysis. The high reactivity of the N-benzoyl aza-DIBO synthesized is demonstrated in a strain-promoted azide-alkyne cycloaddition reaction with an alkyl azide (k=0.38 M(-1) s(-1)).

Mechanism and Kinetics of the Reaction NO3+ C2H4

The reaction of NO(3) radical with C(2)H(4) was characterized using the B3LYP, MP2, B97-1, CCSD(T), and CBS-QB3 methods in combination with various basis sets, followed by statistical kinetic analyses and direct dynamics trajectory calculations to predict product distributions and thermal rate constants. The results show that the first step of the reaction is electrophilic addition of an O atom from NO(3) to an olefinic C atom from C(2)H(4) to form an open-chain adduct. A concerted addition reaction mechanism forming a five-membered ring intermediate was investigated, but is not supported by the highly accurate CCSD(T) level of theory. Master-equation calculations for tropospheric conditions predict that the collisionally stabilized NO(3)-C(2)H(4) free-radical adduct constitutes 80-90% of the reaction yield and the remaining products consist mostly of NO(2) and oxirane; the other products are produced in very minor yields. By empirically reducing the barrier height for the initial addition step by 1 kcal mol(-1) from that predicted at the CBS-QB3 level of theory and treating the torsional modes explicitly as one-dimensional hindered internal rotations (instead of harmonic oscillators), the computed thermal rate constants (including quantum tunneling) can be brought into very good agreement with the experimental data for the overall reaction rate constant.

Interrogating the catalytic mechanism of nanoparticle mediated Stille coupling reactions employing bio-inspired Pd nanocatalysts

To address issues concerning the global environmental and energy state, new catalytic technologies must be developed that translate ambient and efficient conditions to heavily used reactions. To achieve this, the structure/function relationship between model catalysts and individual reactions must be critically discerned to identify structural motifs responsible for the reactivity. This is especially true for nanoparticle-based systems where this level of information remains limited. Here we present evidence indicating that peptide-capped Pd nanoparticles drive Stille C-C coupling reactions via Pd atom leaching. Through a series of reaction studies, the materials are shown to be optimized for reactivity under ambient conditions where increases in temperature or catalyst concentration deactivate reactivity due to the leaching process. A quartz crystal microbalance analysis demonstrates that Pd leaching occurs during the initial oxidative addition step at the nanoparticle surface by aryl halides. Together, this suggests that peptide-based materials may be optimally suited for use as model systems to isolate structural motifs responsible for the generation of catalytically reactive materials under ambient synthetic conditions.

Chemo-, regio-, and diastereoselectivity preferences in the reaction of a sulfur ylide with a dienal and an enone

Mechanistic insights into an interesting class of reaction between sulfur ylides with (i) a dienal, and (ii) an enone, obtained by using density functional theory, is reported. The kinetic and thermodynamic factors responsible for chemo-, regio-, and diastereoselectivities are established by identifying all key transition states and intermediates along the reaction pathway for 1,2-, 1,4-, and 1,6- modes of attack of dimethylsulfonium benzylide to 5-phenylpenta-2,4-dienal. The reaction profiles for 1,2- and 1,4- modes of addition are also evaluated for the reaction between dimethylsulfonium benzylide and pent-3-en-2-one. Our results show that the final outcome of the reaction with both these substrates would be decided by the interplay between kinetic and thermodynamic factors. It is found that the addition of a semi-stabilized ylide to conjugated carbonyl compounds prefers to proceed through a 1,4- (conjugate) pathway under thermodynamic conditions, which is in accordance with the available experimental reports. However, the formation of epoxides via a 1,2- (direct) addition pathway is computed to be equally competitive, which could be the favored pathway under kinetic conditions. Even though the lower barrier for the initial addition step is kinetically advantageous for the direct (or 1,2-) addition pathway, the higher energy of the betaine intermediates--as well as the reversibility of the accompanying elementary step--may disfavor product formation in this route. Thus, high diastereoselectivity in favor of 2,3-trans cyclopropanecarbaldehyde is predicted in the case of the dienal, using the most favored conjugate addition (1,4-addition) pathway. Along similar lines, ylide addition to the enone is identified to exhibit a preference toward conjugate addition over direct (1,2-) addition. The importance of transition state analysis in delineating the controlling factors towards product distribution and diastereoselectivity is established.

ChemInform Abstract: Stereoselective Synthesis of 3(2H)-Dihydrofuranones by Addition of Lithiated Methoxyallene to Chiral Aldehydes.

Lithiated methoxyallene 2 adds to chiral aldehydes such as 2-phenylpropanal and N,N-dibenzylated α-amino aldehydes 4-8 to give products 9-14 in good yields and with excellent anti-selectivity. The stereochemical outcome of these reactions can be explained by the Felkin-Anh model in a straightforward manner. The crude reaction products can either be transformed to enones by hydrolysis with acid or be converted into 2,5-dihydro-3-methoxyfuran derivatives 19-24 by treatment with potassium tert-butoxide in DMSO. The latter can be hydrolyzed to give 3(2H)-dihydrofuranones 25-29. The diastereoselectivity of the initial addition step is transferred to the dihydrofuran derivative without a major change in the isomer ratio. Compounds derived from α-amino aldehydes 5, 6, and 8 are assumed to be enantiomerically pure. Sodium borohydride reductions of and Grignard additions to 3(2H)-dihydrofuranones 27a and 28a demonstrate that these chiral ketones react in a highly diastereoselective manner. In summary, this paper shows that lithiated methoxyallene 2 can serve as a vrey useful equivalent for α,β-unsaturated acyl anions and 1,3-dipolar synthons in asymmetric synthesis

Palladium‐Catalyzed Oligocyclizations of 2‐Bromoalka‐1,(n+m+1)‐dien‐(n+1)‐ynes – Influence of Tether Lengths and Substituents on the Outcome of the Reaction (Part II)

AbstractThe cascade reaction modes and hence the outcomes of the palladium‐catalyzed oligocyclizations of various 2‐bromoalka‐1,(n+m+1)‐diene‐(n+1)‐yne substrates were found to be highly dependent on the tether lengths between the multiple bond fragments, and on the nature of the substituent at the non‐brominated vinylic terminus. Just like 2‐bromododeca‐1,11‐dien‐6‐ynes with their two three‐atom tethers, 2‐bromotrideca‐1,12‐dien‐7‐ynes 8 and 2‐bromotetradeca‐1,13‐dien‐8‐ynes 17, with combinations of four‐ and three‐ as well as five‐ and three‐atom tethers, under Heck‐type reaction conditions undergo, after the initial oxidative addition step, two consecutive n‐exo‐dig and m‐exo‐trig carbopalladations followed by β‐hydride elimination and ensuing 6π‐electrocyclization to furnish tricyclic bisannelated cyclohexadiene derivatives, such as 37 and 40, in moderate yields (30 and 29 %). On the other hand, when 2‐bromoalka‐1,(n+m+1)‐dienynes with a four‐, five‐ or even a six‐atom tether between the bromoene and the yne moiety, and a four‐atom tether between the yne and the terminal ene unit, such as 34, 35 and 36, are subjected to Heck‐type reaction conditions, they undergo a cascade oligocyclization involving a 5‐exo‐trig‐ and ensuing 3‐exo‐trig‐carbopalladation as the fourth and fifth steps before the terminating β‐hydride elimination, eventually leading to tetracyclic skeletons such as 43, 44 and 45 with a bridging three‐membered ring in yields of 74, 76 and 32 %, respectively.

Carbon Nucleophilicities of Indoles in SNAr Substitutions of Superelectrophilic 7-Chloro-4,6-dinitrobenzofuroxan and -benzofurazan

Superelectrophilic 7-chloro-4,6-dinitrobenzofuroxan (DNBF-Cl) and 7-chloro-4,6-dinitrobenzofurazan (DNBZ-Cl) are shown to undergo facile carbon-carbon couplings with a series of weak carbon nucleophiles consisting of a number of differently substituted indoles, 1,2,5-trimethylpyrrole and azulene, in acetonitrile. Despite the fact that steric effects preclude a coplanarity of the donor and acceptor moieties, the resulting substitution products are subject to an intense intramolecular charge transfer. A kinetic study of the various substitutions has been carried out. The absence of a significant dependence of the rates of coupling on the hydrogen or deuterium labeling at the reactive center of the nucleophiles indicates that the reactions take place through an SEAr-SNAr mechanism with the initial nucleophilic addition step being rate-limiting. A vicarious-type substitution is shown to be unreasonable. Referring to Mayr nucleophilicity parameters (N), which have become recently available for a large set of indoles, the electrophilicity of DNBF-Cl and DNBZ-Cl, could be ranked on the general electrophilicity scale E developed by this author (Acc. Chem. Res. 2003, 36, 66). With essentially similar E values of -6.1, these two compounds have an electrophilicity which approaches that of cationic stuctures such as 4-nitrobenzenediazonium cation or tropylium cations. Most important in the context of SNAr substitutions, DNBF-Cl and DNBZ-Cl are 7 orders of magnitude more electrophilic than picryl chloride, the conventional reference electrophile in this field. It is this so far unique behavior which allows the facile coupling of DNBF-Cl and DNBZ-Cl with such weak carbon nucleophiles as indoles. Based on a nice Brönsted-type correlation for 5-X-substituted indoles, the unknown pKaCH values measuring the Brönsted C-basicity of several N-benzylindoles could be readily estimated. The influence of some steric effects in 2-methylindole systems is pointed out.

Enantio- and Diastereoselectivities in Chiral Sulfur Ylide Promoted Asymmetric Aziridination Reactions

Density functional theory investigation on the factors controlling enantio- and diastereoselection in asymmetric aziridination reaction by the addition of chiral bicyclic sulfur ylides to substituted aldimines is presented. High levels of enantioselection are predicted toward the formation of (2S,3S)-cis and (2R,3S)-trans aziridines by the addition of stabilized ylide (R = COMe) respectively to SO2Me and CO2Me protected aldimines. Similarly, high %ee is predicted for the formation of (2S,3R)-cis aziridines from semistabilized (R = Ph) ylide. Moderate to high levels of diastereoselectivity is noticed as well. The present study highlights that a correct prediction on extent of enantioselection requires the knowledge of the activation barriers for elementary steps beyond the initial addition step. In the case of stabilized ylides the ring-closure (or elimination of sulfur compound) is found to be crucial in controlling enantio- and diastereoselection. A cumulative effect of electronic as well as other weak interactions is identified as factors contributing to the relative energies of transition states leading to enantio- and diastereomeric products for the stabilized ylide addition to aldimines. On the contrary, steric control appears quite dominant with semistabilized ylide addition. With the smallest substituent on ylide (R = Me), high enantioselectivity is predicted for the formation of (2R,3R)-trans aziridines although the %de in this case is found to be very low.

Mechanism and Diastereoselectivity of Aziridine Formation from Sulfur Ylides and Imines: A Computational Study

A computational investigation of the title reaction involving semistabilized (R = Ph) and stabilized (R = CO2Me) sulfur ylides has been performed using DFT methods including a continuum model of solvent. Our results provide support for the generally accepted mechanism and are in very good agreement with observed cis/trans selectivities. This study shows that betaine formation is nonreversible, and that selectivity is thereby determined at the initial addition step, in the case of semistabilized ylides. Our analysis indicates moreover that addition TS structures are governed by the steric strain induced by the N-sulfonyl group, which favors the transoid approach in the case of syn betaine formation and the cisoid mode of addition in anti TSs. The observed low trans selectivity is accounted for by the favorable Coulombic interactions and stabilization by C-H...O hydrogen bonding allowed in the cisoid anti addition TS. In the case of stabilized ylides, the endothermicity of betaine formation combined with the high barrier to ring closure render the elimination step rate- and selectivity-determining. Accordingly, the low cis selectivity observed in stabilized ylide reactions is explained by the lower steric strain in the elimination step generated by the formation of the cis aziridine (as compared to the trans case).

Stereoselective Cyclopropanation of 2‐[(S)‐(4‐Methylphenyl)sulfinyl]cyclopent‐2‐en‐1‐one with Sulfur Ylides and α‐Halo Carbanions. Preliminary Communication

AbstractThe cyclopropanation of the title compound (S)‐2 with various sulfur ylides has been examined. The reaction with methylenesulfonium ylides gave the corresponding cyclopropanes 4 with low diastereoselectivity. The formation of the second product 5 arising from the subsequent methylenation of the CO group was also observed. A clean cyclopropanation of (S)‐2 took place with ethyl (dimethylsulfanylidene)acetate affording the cyclopropanes 6, with high π‐facial selectivity, but low endo/exo ratio. A high endo/exo selectivity, but low π‐facial selectivity was observed in the reaction of (S)‐2 with (2‐ethoxy‐2‐oxoethyl)(diphenyl)sulfonium tetrafluoroborate. The use of α‐bromoacetate carbanion as the cyclopropanation reagent resulted in the formation of 6 with very high facial and endo/exo‐selectivity. In a proposed explanation of the stereochemical outcome of the cyclopropanations investigated, the ground‐state conformation of the sulfoxide 2 and the transition‐state structure of the initial addition step were taken into account.

Mechanistic Pathways of the Hydroxyl Radical Reactions of Quinoline. 1. Identification, Distribution, and Yields of Hydroxylated Products

The mechanistic details of the hydroxyl radical-induced transformations of quinoline have been elucidated. The nature and distribution of the final products have provided insight into the preferential attack of the hydroxyl radicals at different sites on the aromatic rings. Hydroxylated products at all of the carbon atoms but one, C2, have been observed and quantified following controlled radiolysis of N2O-purged aqueous quinoline solutions. The difference in the growth pattern and the lifetime of the monohydroxylated products under radiolytic conditions, as well as the formation of high-molecular-weight products (e.g., quinoline dimers), shows the complexity of the OH reaction pathways. The radiolytic yields (G values) for the degradation of the quinoline and the formation of the hydroxylated products are calculated in the absence and in the presence of an oxidant, K3Fe(CN)6. The addition of K3Fe(CN)6 changes only the distribution of the hydroxylated products. These experiments indicate that the nature of the hydroxylated products is determined in the initial addition step of the reaction of the hydroxyl radical with quinoline, whereas the chemistry of the OH adducts is relevant to the distribution of the final products. The discrepancy between the products of -radiolysis and the photo-Fenton reaction of quinoline is also discussed.