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Tertiary cyclohexyl cations. Definitive evidence for the existence of isomeric structures (hyperconjomers)
Abstract
The 1-methyl-1-cyclohexyl cation 1 has previously been proposed to exist in superacid solution as a rapidly equilibrating pair of structures, one isomer involving C–C hyperconjugation, and a counterpart with axial C–H hyperconjugation (hyperconjomers). Using a combination of three techniques, which successfully compare theoretical results with experimental data, we have now obtained virtual proof for this concept. These three calculational procedures involve matching the experimental energy difference for the C–C and C–H hyperconjomers of 1, together with the cis-3,5-dimethyl 2 and 4,4-dimethyl 3 analogs of 1, to an accuracy of ±2 kJ mol−1 (solvation-simulation studies), a successful simulation of the α-d4 equilibrium isotope effects for the 1, 2 and 3 cation systems, and, finally, a close simulation of the average 13C NMR spectra for mixtures of these C–C and C–H hyperconjomers in the 1, 2 and 3 systems. These results have interesting implications for solvolysis studies of tertiary cyclohexyl systems, a full discussion of which is presented.
... Two distinct chair conformations, C-C and C-H hyperconjugatively interacting cyclohexyl ions were suggested to be involved in rapid equilibrium in superacid solution. The ions were also investigated by Sorensen, Schleyer and co-workers using ab initio/GIAO-MP2 methods [20,21]. We have accordingly calculated the Using MP2/cc-pVTZ geometries structures of the cyclohexyl cation at the MP2/cc-pVTZ level. ...
... Computed δ 13 C of the C1 (and C4) carbon of 18 is 137.8 and is also consistent with the hydrogen-bridged structure. The cation 19 has been prepared and extensively studied by Sorensen et al. [19][20][21]. Two distinct chair conformations, C-C and C-H hyperconjugatively interacting cyclohexyl ions were suggested to be involved in rapid equilibrium in the superacid solutions. ...
Various structures of the cyclopentyl cation were computed at the MP2/cc-pVTZ and CCSD (T)/cc-pVTZ levels. Energetically, the classical cyclopentyl cation 1 and the 1,2-hydrogen-bridged structure 3 were found to be almost identical. The structures and energies of the cyclohexyl and cycloheptyl cations were also calculated at the MP2/cc-pVTZ level. The σ-delocalized nonclassical ion 16 was found to be the lowest energy structure for the cycloheptyl cation. The ¹³C NMR chemical shifts of the ions were also computed and compared with the experimental results.
... 293 The role of hyperconjugation increases dramatically in cyclohexyl cations where it has a profound effect on structure and stability. An elegant study of Rauk and coworkers 294,295 reported the different hyperconjugation stabilization patterns lead to the formation of two chair conformers of 1-Me-1-cyclohexyl cation where the carbocation p-orbital is oriented either "axially" or "equatorially." These conformers, called "hyperconjomers," have distinctly different modes of hyperconjugative stabilization. ...
This review outlines the role of hyperconjugative interactions in the structure and reactivity of organic molecules. After defining the common hyperconjugative patterns, we discuss the main factors controlling the magnitude of hyperconjugative effects, including orbital symmetry, energy gap, electronegativity, and polarizability. The danger of underestimating the contribution of hyperconjugative interactions are illustrated by a number of spectroscopic, conformational, and structural effects. The stereoelectronic nature of hyperconjugation offers useful ways for control of molecular stability and reactivity. New manifestations of hyperconjugative effects continue to be uncovered by theory and experiments.
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• Structure and Mechanism > Molecular Structures
• Software > Molecular Modeling
• Structure and Mechanism > Reaction Mechanisms and Catalysis
21-homododecahedryl cation is a unique system in terms of its complete fluxionality based on two different rearrangements. In this work we report the quantum tunneling effects that drive the reactions...
Condensation of α-pinene derived p-menta-1,8-diene-5,6-diol (diol) with decanal was studied for the first time over modified halloysite nanotubes (HNT). The yield of the desired hexahydro-2H-chromene-4,8-diol with analgesic activity was 76–80% practically not depending on the catalyst type, while selectivity to 4S-isomer decreased, and to 4R-isomer increased with increasing acidity. The highest selectivity to 4S-diastereomer (48.1%) on halloysite is a result of weak acidity of this catalyst. DFT optimization of the key intermediate structure shows that the nucleophile attack proceeds at the equatorial position with the 4S-diastereomer formation, which was preferred on halloysite. On strong Brønsted (Amberlyst-15) and Lewis (scandium triflate) acids the target product yield did not exceed 37% because of dehydration. Halloysite nanocatalysts displayed a stable performance. In the case of diol reaction with a set of carbonyl compounds, the yields of hexahydro-2H-chromene-4,8-diols and the ratio of its 4S/4R isomers were significantly higher than on other catalysts.
Results of density functional calculations on rearrangements of potential biosynthetic precursors to the sesquiterpenoid illisimonin A reveal that only some possible precursors, those with certain specific oxidation patterns, are rearrangement-competent.
Glycosylation reactions were performed on a series of bicyclic C2-substituted pyranoside models to isolate and analyze factors that control the glycosylation stereoselectivities observed in carbohydrates. The bent bond / antiperiplanar hypothesis (BBAH) orbital model rationalizes all these results by considering hyperconjugation interactions between groups at C2 and the two τ bonds (bent bonds) of oxocarbenium ion intermediates formed under the glycosylation conditions. According to the BBAH, nucleophiles add to the oxocarbenium intermediates by SN2-like antiperiplanar displacement of the weaker of its two τ bonds.
The glycosylation stereoselectivities for a series of bicyclic furanoside models have been carried out in the presence of weak nucleophiles. These results were analyzed through the bent bond / antiperiplanar hypothesis (BBAH) orbital model in order to test its validity. According to the BBAH, incoming nucleophiles displace one of the two bent bonds of bicyclic oxocarbenium ion intermediates in antiperiplanar fashion. The glycosylation stereoselectivity is then governed by displacement of the weaker bent bond as determined by the presence of electron-withdrawing or donating substituents at C2. Overall, the BBAH analysis expands Woerpel's "inside/outside attack" glycosylation model by considering the stereoelectronic influence of neighbouring electron-withdrawing and donating groups on the nucleophilic addition to oxocarbenium ion intermediates.
Polyene cyclisations are a powerful method for the direct generation of molecular complexity. This paper describes the use of computational methods to investigate the stereoselectivity of cationic polyene cyclisations of...
A biomimetic cationic structural rearrangement of the oleanolic acid framework is reported for the gram‐scale synthesis and structural reassignment of justicioside E aglycone. The mechanism of the putative biosynthetic rearrangement is investigated with kinetic, computational, and synthetic approaches. The precursor to rearrangement was accessed through two strategic advancements: (1) synthesis of a 1,3‐diketone via oxidation of a β‐silyl enone, and (2) diastereoselective 1,3‐diketone reduction to form a syn‐1,3‐diol using SmI2 with PhSH as a key additive.
A biomimetic cationic structural rearrangement of the oleanolic acid framework is reported for the gram‐scale synthesis and structural reassignment of justicioside E aglycone. The mechanism of the putative biosynthetic rearrangement is investigated with kinetic, computational, and synthetic approaches. The precursor to rearrangement was accessed through two strategic advancements: (1) synthesis of a 1,3‐diketone via oxidation of a β‐silyl enone, and (2) diastereoselective 1,3‐diketone reduction to form a syn‐1,3‐diol using SmI2 with PhSH as a key additive.
The bent bond/antiperiplanar hypothesis (BBAH) is used to propose a mechanism-based orbital model for the facial selectivity of sigmatropic hydrogen shifts under both thermal and photochemical conditions. The BBAH analysis of these concerted rearrangements invokes transient vibrationally excited singlet diradicals in both 4n and 4n+2 polyenes.
The bent bond / antiperiplanar hypothesis (BBAH) has been applied to the thermal rearrangements of cyclooctatetraene and related C8H8 isomers. This novel orbital model shows that pyramidal singlet diradical intermediates produced from thermal vibrational states of C8H8 isomers accounts their chemical reactivity.
The enantiopure reagent menthyl chloride (2) is generally prepared from (-)-(1R)-menthol (1) with Lucas' reagent (ZnCl2 in conc. aqueous HCl) in a stereoretentive reaction that appeared to be free from accompanying rearrangements. The same was assumed for a recent synthesis of 2 via TiCl4-catalyzed extrusion of SO2 from menthyl chlorosulfite (3). The products from both syntheses have now been analyzed by quantitative 1H and 13C NMR methods and all reaction components have been identified down to the ≤0.5 mol% level. Either reaction is accompanied by cationic rearrangement to the considerable extent of 18-25 mol%. Besides the expected 2, neomenthylchloride (4) and five rearrangement products have been identified, among them three regioisomeric tertiary chloromenthanes (9, 10, 11), and both a secondary (12) and tertiary chloride (16) derived from ψ-menthane (1-isobutyl-3-methylcyclopentane). A scheme of rearrangement pathways starting from a common menthyl carbenium ion pair is derived. The effect of purification protocols on crude 2 has been studied quantitatively. Either selective solvolysis of tertiary sideproducts (98 mol% purity) or low-temperature crystallization (≥97 mol% purity) was successful. An improved, scalable synthesis of 2 via the catalytic rearrangement of chlorosulfite 3 is reported.
The stereoselectivity of nucleophilic addition on oxocarbenium ions derived from the bicyclic pyranoside model with or without a C2-OR group can be understood through the use of the bent-bond and the antiperiplanar hypothesis in conjunction with the concept of hyperconjugation as an alternative interpretive model of structure and reactivity.
This chapter outlines the variety of common stereoelectronic effects where donor and acceptor orbitals are separated by a single bond. The unifying feature of such orbital interactions is that they can be switched on or off via rotation around the single bond. Orbital interactions are complex and depend on the combination of stabilizing delocalizations, sterics, and electrostatics. The chapter focuses on stabilizing effects, such as hyperconjugation and conjugation, that control energies and conformations of reactive intermediates and such common organic functionalities as acyclic and cyclic alkanes, alkenes, alkynes, dienes, diynes, alkyl halides, ethers, carbohydrates, vinyl ethers, amines, enamines, ketones, aldehydes, esters, carbonates, amides, carbamates, ureas etc. The wide variety of stereoelectronic interactions across the broad spectrum of functional groups is classified within several well-defined classes of interactions (σ/σ*, σ/π*//π/σ*, n/σ*, n/π* and π/π*). Detailed conformational analysis is provided for many of the above functionalities through the prism of stereoelectronic factors. This chapter also introduces a number of classic stereoelectronic effects on reactivity such as the gauche effect, the anomeric and homoanomeric effects, the β-silicon and β-tin effects etc. Detailed analysis illustrates how stereoelectronic effects of a different nature can coexist and lead to multiple layers of consequences for structure and reactivity.
The degenerate rearrangement in the 21-homododecahedryl cation (1) has been studied via density functional theory computations and Born-Oppenheimer Molecular Dynamics simulations. Compound 1 can be described as a highly fluxional hyperconjugated carbocation. Complete scrambling of 1 can be achieved by the combination of two unveiled barrierless processes. The first one is a "rotation" of one of the six-membered rings via a 0.8 kcal·mol(-1) barrier, and the second one is a slower interconvertion between two hyperconjomers via an out-of-plane methine bending (ΔG(⧧) = 4.0 kcal·mol(-1)).
Trimethylborane (1), triethylborane (2), 1,3-dimethyl-1-boracyclopentane (3), 1-methyl-1-boracyclohexane (4), 9-methyl- and 9-ethyl-9-borabicyclo[3.1.1] nonane [5(Me) and 5(Et)], and 1-boraadamantane (6) were studied by 11B and 13C NMR spectroscopy with respect to coupling constants 1J(13C,11B) and 1J( 13C,13C). Results of DFT calculations at the B3LYP/6-311+g(d,p) level of theory show satisfactory agreement with the experimental data. Hyperconjugation arising from C-C σ bonds adjacent to the tricoordinate boron atom is indicated, in particular for 1-boraadamantane (6), by the optimised calculated structures, and by the experimental and calculated data 1J(13C,13C). The calculated magnitude of 1J(13C,1H) for carbon atoms adjacent to boron becomes significantly smaller if the optimised structures suggest hyperconjugative effects arising from these C-H bonds.
The chemistry of superacids has developed in the last two decades into a field of growing interest and importance. Now available in a new expanded second edition, this definitive work on superacids offers a comprehensive review of superacids and discusses the development of new superacid systems and applications of superacids in the promotion of unusual reactions. Covering Bronsted and Leurs superacids, solid superacids, carbocations, heterocations, and catalyzed reactions, this timely volume is invaluable to professionals, faculty, and graduate students in organic, inorganic, and physical chemistry.
Winner of the PROSE Award for Chemistry & Physics 2010. Acknowledging the very best in professional and scholarly publishing, the annual PROSE Awards recognise publishers' and authors' commitment to pioneering works of research and for contributing to the conception, production, and design of landmark works in their fields. Judged by peer publishers, librarians, and medical professionals, Wiley are pleased to congratulate Professor Ian Fleming, winner of the PROSE Award in Chemistry and Physics for Molecular Orbitals and Organic Chemical Reactions. Molecular orbital theory is used by chemists to describe the arrangement of electrons in chemical structures. It is also a theory capable of giving some insight into the forces involved in the making and breaking of chemical bonds-the chemical reactions that are often the focus of an organic chemist's interest. Organic chemists with a serious interest in understanding and explaining their work usually express their ideas in molecular orbital terms, so much so that it is now an essential component of every organic chemist's skills to have some acquaintance with molecular orbital theory. Molecular Orbitals and Organic Chemical Reactions is both a simplified account of molecular orbital theory and a review of its applications in organic chemistry; it provides a basic introduction to the subject and a wealth of illustrative examples. In this book molecular orbital theory is presented in a much simplified, and entirely non-mathematical language, accessible to every organic chemist, whether student or research worker, whether mathematically competent or not. Topics covered include: Molecular Orbital Theory. Molecular Orbitals and the Structures of Organic Molecules. Chemical Reactions - How Far and How Fast. Ionic Reactions - Reactivity. Ionic Reactions - Stereochemistry. Pericyclic Reactions. Radical Reactions. Photochemical Reactions. This expanded Reference Edition of Molecular Orbitals and Organic Chemical Reactions takes the content and the same non-mathematical approach of the Student Edition, and adds extensive extra subject coverage, detail and over 1500 references. The additional material adds a deeper understanding of the models used, and includes a broader range of applications and case studies. Providing a complete in-depth reference for a more advanced audience, this edition will find a place on the bookshelves of researchers and advanced students of organic, physical organic and computational chemistry. The student edition of Molecular Orbitals and Organic Chemical Reactions presents molecular orbital theory in a simplified form, and offers an invaluable first textbook on this important subject for students of organic, physical organic and computational chemistry. Further information can be viewed here. "These books are the result of years of work, which began as an attempt to write a second edition of my 1976 book Frontier Orbitals and Organic Chemical Reactions. I wanted to give a rather more thorough introduction to molecular orbitals, while maintaining my focus on the organic chemist who did not want a mathematical account, but still wanted to understand organic chemistry at a physical level. I'm delighted to win this prize, and hope a new generation of chemists will benefit from these books."
A Ritter‐like coupling reaction of cyclic alcohols and both aryl and alkyl nitriles to form amides catalyzed by copper(II) triflate is described. These reactions proceed in good yields under mild and often solvent‐free conditions. With 2‐ and 3‐substituted cycloalkanols, amide products are formed with near complete retention of configuration. This is likely due to fast nucleophilic capture of non‐planar carbocations (hyperconjomers) stabilized by ring hyperconjugation. A critical aspect of this novel catalytic cycle is the in situ activation of the alcohol substrates by thionyl chloride to form chlorosulfites.
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Quantum chemical calculations are used to assess various means of lowering the barrier for the dyotropic rearrangement previously proposed to occur during the carbocation rearrangement process promoted by pentalenene synthase. Several means of lowering this barrier, including a stepwise pathway for dyotropic rearrangement, are uncovered.
Chlorosulfites prepared in situ using thionyl chloride react with nitrile complexes of titanium (IV) fluoride to give a one-pot conversion of alcohols into amides. For the first time, amides are obtained from cyclic alcohols with stereoretention. Critical to the design of these new Ti(IV) reactions has been the use of little explored Ti(IV) nitrile complexes which are thought to chelate chlorosulfites in the transition state to create a carbocation that is rapidly captured by the nitrile nucleophile via a front-side attack mechanism.
The SN2 reaction (bimolecular nucleophilic substitution) is a well-known chemical transformation that can be used to join two smaller molecules together into a larger molecule or to exchange one functional group for another. The SN2 reaction proceeds in a very predictable manner: substitution occurs with inversion of stereochemistry, resulting from the 'backside attack' of the electrophilic carbon by the nucleophile. A significant limitation of the SN2 reaction is its intolerance for tertiary carbon atoms: whereas primary and secondary alcohols are viable precursor substrates, tertiary alcohols and their derivatives usually either fail to react or produce stereochemical mixtures of products. Here we report the stereochemical inversion of chiral tertiary alcohols with a nitrogenous nucleophile facilitated by a Lewis-acid-catalysed solvolysis. The method is chemoselective against secondary and primary alcohols, thereby complementing the selectivity of the SN2 reaction. Furthermore, this method for carbon-nitrogen bond formation mimics a putative biosynthetic step in the synthesis of marine terpenoids and enables their preparation from the corresponding terrestrial terpenes. We expect that the general attributes of the methodology will allow chiral tertiary alcohols to be considered viable substrates for stereoinversion reactions.
This chapter describes the recent applications of quantum chemical calculations of nuclear magnetic resonance (NMR) chemical shifts and spin–spin coupling constants in carbocation chemistry. Calculation of NMR parameters, such as chemical shift and spin–spin coupling constants has evolved into an important tool in carbocation chemistry as well as in related fields, such as silylenium ion and borane. Despite the successful prediction of chemical shifts for a great structural variety of carbocations some difficulties have been encountered for vinyl cations. Quantum chemical calculations of NMR parameters have provided detailed information on structures and stabilization modes of carbocations, and have provided deeper insights into intriguing questions and long-standing controversies in carbocation chemistry. The everlasting need for better experimental tools and theoretical methods to explore the field of carbocation chemistry had also a significant influence on the further development of ab initio methods for the calculation of NMR shielding and indirect spin–spin coupling constants. Carbocation chemistry thus, serves as a forerunner for a close integration of experimental and computational approaches in all areas of chemistry.
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Patrick Pale was born in Charleville (Ardennes), studied at the University of Champagne-Ardenne, where he obtained a Ph. D. in 1982 under the direction of Prof. J. P. Pete and J. Muzart. After an industrial stay in a pharmaccutical company, he joined the laboratories of Prof. L. Ghosez at Louvain-La-Neuve in Belgium for a postdoctoral work on synthetic applications of azadienes. In 1984, he returned to the University of Champagne-Ardenne as a CNRS fellow. Working on rearrangements and reaction mechanisms, he obtained a “Doctorat d'Etat” in 1987, then a research associate position at Harvard University in the group of Prof. George Whitesides in 1988–1989. He returned to the University of Champagne-Ardenne, and took up his present position as Professor in Organic Chemistry at the University L. Pasteur Strasbourg in September 1994. Subsequently, he was awarded Professor at the Institut Universitaire de France from 1996 to 2001. His scientific interests include total synthesis of bioactive compounds, organometallic chemistry, asymmetric synthesis, and catalysis, in particular carbohydrate chemistry and enzymatic chemistry.
The deuterium isotope effects on the 13C chemical shifts and the electronic structure of the molecules, were analyzed. It was observed that the nuclear magnetic shielding depends on the vibrationally and rotationally averaged bond lengths and bond angles. The prerequisite for observing separate signals for the H- and the D species was to have slow exchange on the NMR time scale. Results show that the largest effects occurred in the bond in which the subsituted atom was directly involved.
Computational studies of competing five- and six-membered cyclisation of alkenyloxiranes 1a–d show that intramolecular reaction of a protonated oxirane and alkene is a concerted, single-step, exothermic process. The reactions proceed via reactant-like transition states, but where the oxirane C–O bond is considerably stretched. Two factors are seen to affect the regiochemistry: (1) stabilisation of the transitory positive charge in the transition state favours cyclisation to the more highly substituted oxirane carbon; and (2) there is an inherent stereoelectronic preference for six-membered cyclisation over five-membered cyclisation. The inherent preference for six-membered cyclisation has a parallel in Baldwin's rules for six-membered ring closure of a carbocation with an alkene, rather than Baldwin's rule for intramolecular nucleophilic reaction of three-membered rings, suggesting that the protonated oxirane mimics a carbocation. The electronic and stereoelectronic effects for cyclisation are modified by steric interactions of axial methyl groups. These systems provide a model for the A-ring cyclisation of oxidosqualene.
Saturated six-membered heterocyclic rings can be found in natural products, drugs, and polymers. The methodologies for studying the conformers at equilibrium and their rates of interconversion are mainly based on nuclear magnetic resonance (NMR) spectroscopy. This chapter provides the conformational analysis and stereodynamics of saturated heterocyclic six-membered rings. The cyclohexane-like rings are characterized by the presence of various nonplanar conformations: chair, boat, and twist conformations. The conformational equilibria in six methylcyclohexanes are examined in the chapter using the temperature dependence of the 13C chemical shifts at temperatures above the coalescence point. The conformational enthalpy (∆H°), entropy (∆S°) and free energy (∆G°) of methyl-, ethyl-, and iso-propyl-cyclohexane for monosubstituted and polysubstituted cyclohexanes in solution are examined in the chapter both experimentally and computationally. The stereochemistry, physical and chemical properties, and some transformations of 1,3-oxathianes—especially alkyl substituent effects on the preferred conformers—are also reviewed in the chapter. The synthesis and conformational analysis of the condensed-skeleton saturated heterocycles are also described in the chapter. The preferred conformers of six-membered rings with one exo- or endo-double bond in the solid state are tabulated in the chapter.
Tertiary (2-propyl)cyclopentyl and (2-propyl)cyclohexyl carbocations were investigated by 13C NMR spectroscopy in superacid solution. Both ions undergo fast nondegenerate 1,2-hydride shifts to the corresponding 2-cycloalkyl-2-propyl cations. The direction of these equilibria depends on the size of the ring. The more stable isomer of the (2-propyl)cyclopentyl cation has the formal positive charge at the endocyclic carbon atom, while the more stable isomer of the (2-propyl)cyclohexyl cation has the formal charge at the exocyclic carbon atom. The dynamic NMR results were confirmed by NMR spectroscopic measurement of the equilibrium isotope effects and rationalized by quantum chemical calculations.
The C1 nonamethylcyclopentyl cation minimum undergoes complete methyl scrambling in SbF5 with a 7 kcal/mol barrier. This corresponds to the rate-limiting conformational interconversion of enantiomeric hyperconjomers via a Cs transition structure (above right). A remarkable, more rapid, second process only exchanges methyls within sets of four and five (blue and red, see above), as has been observed experimentally at low temperatures. The computed ∼2 kcal/mol barrier involves a Cs [1s,2s] sigmatropic methyl shift transition structure (above left).
A mild chlorination reaction of alcohols was developed using the classical thionyl chloride reagent but with added catalytic titanium (IV) chloride. These reactions proceeded rapidly to afford chlorination products in excellent yields and with preference for retention of configuration. Stereoselectivities were high for a variety of chiral cyclic secondary substrates including sterically hindered systems. Chlorosulfites were first generated in situ and converted to alkyl chlorides by the action of titanium tetrachloride which is thought to chelate the chlorosulfite leaving group and deliver the halogen nucleophile from the front face. To better understand this novel reaction pathway, an ab initio study was undertaken at DFT level of theory using two different computational approaches. This computational evidence suggests that while the reaction proceeds through a carbocation intermediate, this charged species likely retains pyramidal geometry existing as a conformational isomer stabilized through hyperconjugation (hyperconjomers). These carbocations are then essentially "frozen" in their original configurations at the time of nucleophilic capture.
Nucleophilic addition of water and of methanol to 3,6-diamino-2,4,5,7-tetrabromo-9-[2-(methoxycarbonyl) phenyl]-9H-xanthen-9-ylium, 4BrR123, yields, respectively, xanthyl, 2-(3,6-diamino-2,4,5,7-tetrabromo-9-hydroxy-9H-xanthen-9-yl) benzoate, HO4BrR123 and, xanthyl, 2-(3,6-diamino-2,4,5,7-tetrabromo-9-methoxy-9H-xanthen-9-yl) benzoate, MeO4BrR123. The novel experimental results are addressed theoretically. The Linear Free Energy Relationship, LFER, Second Order Perturbation Theory analysis of the Natural Bond Orbital, NBO, and Quantum Theory of Atoms in Molecules, QTAIM, lead to the same conclusion: the electron-withdrawing effect of bonded Br atoms in 4BrR123 enhances extremely molecular electrophilicity, as compared to 3,6-diamino-9-[2-(methoxycarbonyl) phenyl]-9H-xanthen-9-ylium, R123. The reactivity of these diaminoxanthylium cations is discussed in the context of local and global softness in extended conjugated systems.
This review outlines the ubiquitous nature of hyperconjugative interactions and their role in the structure and reactivity of organic molecules. After defining the common hyperconjugative patterns, we discuss the main factors controlling the magnitude of hyperconjugative effects, including orbital symmetry, energy gap, electronegativity, and polarizibility. The danger of underestimating the magnitude of hyperconjugative interactions are illustrated by a number of spectroscopic, conformational, and structural effects. Through the use of advanced computational techniques, the true role of hyperconjugative effects, as it pertains to their influence on stereoelectronics, conformational equilibria, and reactivities relative to other electronic effects, continue to be uncovered. © 2011 John Wiley & Sons, Ltd. WIREs Comput Mol Sci 2011 1 109–141 DOI: 10.1002/wcms.6
This article is categorized under: Structure and Mechanism > Molecular Structures
The acid-catalyzed addition of CH3(18)OH to 2-methylene-adamantanes bearing a chlorine atom in the 4-equatorial (1e) or 4-axial (1a) position has been investigated in the gas phase, at 760 Torr, in the 40-120 degrees C temperature range. Two different experimental approaches were employed: (1) by adding neutral CH3(18)OH to the 2-methyl-4-Cl-adamant-2-yl cation, generated by protonation of the corresponding 2-methylene-4-Cl-adamantane (the extracomplex reaction) and (2) by reaction of 2-methylene-4-Cl-adamantane with CH3(18)OH2+, generated by methylation of H2(18)O (the intracomplex reaction). The crucial role of the nature of the noncovalent intermediates involved along the reaction coordinates emerges from the difference between the results obtained in the extracomplex and intracomplex reactions for both substrates investigated. The kinetic and stereochemical results indicate that the 4-Cl substituent plays a different role depending on its equatorial or axial orientation. Examination of the experimental results in the light of MP2/6-31G* theoretical calculations provides important information about the intrinsic factors governing the facial diastereoselectivity of trigonal carbocations. The effects due to differential face solvation phenomena emerge from the comparison of the present gas-phase results with those obtained from strictly related studies in solution.
In this paper, we describe theoretical studies, using gas-phase quantum chemical calculations, on carbocationic rearrangement pathways leading to the sesquiterpenes sativene, cyclosativene, alpha-ylangene, and beta-ylangene. For all four sesquiterpene natural products, viable pathways are presented, and these are compared both to mechanistic proposals found in the literature, and in certain cases to alternative stereochemical and rearrangement possibilities, thus providing a basis for comparison to experimental results. We find that these four sesquiterpenes likely arise from a common bicyclic intermediate and, furthermore, that the computed pathways are mostly in agreement with previous mechanistic proposals, although the few differences that we have uncovered are significant. Additionally, the potential energy profiles of the pathways are found to be very flat, supporting the notion that following the initial ionization of farnesyl diphosphate, minimal enzymatic intervention may be required for the generation of such sesquiterpenes.
Oligomeric o-aryleneethynylenes with three triple bonds undergo cascade radical transformations in reaction with a Bu 3SnH/AIBN system. These cascades involve three consecutive cycle closures with the formation of substituted benzo[ a]indeno[2,1- c]fluorene or benzo[1,2]fluoreno[4,3- b]silole derivatives. The success of this sequence depends on regioselectivity of the initial attack of the Bu 3Sn radical at the central triple bond of the o-aryleneethynylene moiety. The cascade is propagated through the sequence of 5-exo-dig and 6-exo-dig cyclizations which is followed by either a radical attack at the terminal Ar substituent or radical transposition which involves H-abstraction from the terminal TMS group and 5-endo-trig cyclization. Overall, the transformation has potential to be developed into an approach to a new type of graphite ribbons.
The chair 4-tetrahydropyranyl cation and the 4-quinuclidinyl cation are shown to be energy minima and to be delocalized, with exceptionally long CH2CH2 bonds, according to B3LYP/6-31G* calculations; the implications for Prins cyclizations, Cope rearrangements, and Grob fragmentations are discussed.
The secondary alpha-deuterium kinetic isotope effect (alpha-kie) for the solvolysis of (Z)-5-trimethylstannyl 2-adamantyl p-bromobenzenesulfonate in 97% w/w aqueous 2,2,2-trifluoroethanol (97T) at 25 degrees C has been measured (k(H)/k(D) = 1.33). The alpha-kie is abnormally high compared to the value of 1.23 for the corresponding limiting S(N)1 solvolysis of 2-adamantyl p-bromobenzenesulfonate, which proceeds via an extended ion-pair mechanism. A novel mechanism for the solvolysis of the tin compound is proposed that accommodates not only the high alpha-kie but also the absence of internal return.
The model reaction between the (R)-1,3-dimethyl-1-cyclohexyl cation (I) and methanol has been investigated under gas-phase radiolytic conditions (750 Torr; 25-120 degrees C) with the aim of evaluating the intrinsic factors that govern the facial selectivity of biased carbocations. The peculiarity of the experimental approach allows the formation of different CH(3) (18)OH.I ionic adducts. Subsequent conversion of these adducts to give the corresponding E/Z covalent products follows different reaction coordinates, which are characterized by their own activation parameters. On the grounds of density functional theory (DFT) results, several [CH(3)OH.I] structures have been located on the relevant potential-energy surface (PES). The experimental results point to a gas-phase facial selectivity, which is mainly governed by entropic factors that arise as a result of the occurrence of different noncovalent ion-molecule "facial adducts" (FA). The formation of FAs may also play an important role in both the reaction dynamics and the positional selectivity. The present results cannot be interpreted by any of the models based on solution-phase experiments.
The diastereofacial selectivity of 2-methyl-5-X-adamant-2-yl cations IX (X = CN, Cl, Br, CH3O, COOCH3, C6H5, CH3, and (CH3)3Sn) toward methanol has been investigated in the gas phase at 750 Torr and in the 40-120 degrees C temperature range and compared with that of IF (X = F) and ISi (X = (CH3)3Si) measured previously under similar conditions. Detailed analysis of the energy surface of the IMe (X = CH3) ion reveals that the activation barrier of its syn addition to methanol is significantly lower than that of the anti attack. In the 40-100 degrees C range, such a difference is strongly reduced by adverse entropic factors which are large enough to invert the IMe diastereoselectivity from syn to anti at T > 69 degrees C. The behavior of IMe diverges markedly from that of IF and ISi. Large adverse entropic factors account for the predominant syn diastereoselectivity observed in the reaction with IF (X = F), notwithstanding the anti enthalpy barrier is lower than the syn one. Adverse entropy plays a minor role in the reaction with ISi (X = (CH3)3Si) which instead exhibits a preferred anti diastereoselectivity governed by the activation enthalpies. Depending on the electronic properties of X, the kinetic behavior of the other IX ions obeys one of the above models. The gas-phase diastereoselectivity of IX ions responds to a subtle interplay between the sigma-hyperconjugative/electrostatic effects of the X substituent and the activation entropy terms. sigma-Hyperconjugation/field effects determine the pyramidal structure and the relative stability of the syn and anti conformers of IX as well as the relative stability of their addition transition structures and their position along the reaction coordinate. The diastereoselectivity of IX in the gas phase is compared with that measured in solution and with theoretical predictions.
A combination of electronic, structural, and energetic analyses shows that a somewhat larger intrinsic donor ability of the C-H bonds compared to that of C-C bonds can be overshadowed by cooperative hyperconjugative interactions with participation of remote substituents (double hyperconjugation or through-bond interaction). The importance of double hyperconjugation was investigated computationally using two independent criteria: (a) relative total energies and geometries of two conformers ("hyperconjomers") of delta-substituted cyclohexyl cations (b) and natural bond orbital (NBO) analysis of electronic structure and orbital interactions in these molecules. Both criteria clearly show that the apparent donor ability of C-C bonds can vary over a wide range, and the relative order of donor ability of C-H and C-C bonds can be easily inverted depending on molecular connectivity and environment. In general, relative donor abilities of sigma bonds can be changed by their through-bond communication with remote substituents and by greater polarizability of C-X bonds toward heavier elements. These computational results can be confirmed by experimental studies of conformational equilibrium of delta-substituted cyclohexyl cations.
The mechanism of the degenerate 1,5-hydride shift in 2,6-dimethyl-2-heptyl cations has been investigated using ab initio MP2 and density functional theory (DFT) hybrid (B3LYP) calculations. The potential-energy profile for the 1,5-hydride shift consists of three minima corresponding to two equivalent acyclic carbocations and one symmetrically mu-hydrido-bridged carbocation, while two equivalent unsymmetrically hydrido-bridged carbocations were located as transition-state structures. The calculated relative energy differences between acyclic carbocations and symmetrically mu-hydrido-bridged structure are significantly affected by introduction of alkyl and (CH2)n-substituents at the C4 position of the 2,6-dimethyl-2-heptyl cation structure. DFT self-consistent isodensity polarizable continuum method (SCI-PCM) and MP2 PCM continuum methods have been used to calculate the effect of solvation on geometries and relative energies of the species involved in the 1,5-hydride shift. It is found that relative energies of acyclic and mu-hydrido-bridged carbocation structures as well as the energy barriers for 1,5-hydride shifts are in accord with experimental data if solvation effects are taken into account.
Details are reported of a general synthesis of the epimeric trans,trans,trans-tricyclo[7.3.1.0]tridecan-3-ols and the corresponding toluene-p-sulphonates, (5a and b). Both compounds react in buffered acetic acid slightly more slowly than simpler unbridged axial and equatorial cyclohexyl toluene-p-sulphonates, but the axial: equatorial epimeric rate ratio is very similar at 3.4 : 1 (50 °C) and is quite different from the divergent values obtained for bridged systems. The epimeric rate ratio is even smaller in 97 : 3 (w/w) hexafluoropropan-2-ol–water (97HFIP), 1 : 1 at 25 °C, and the equatorial compound is estimated to be the more reactive in this medium below ca. 6 °C. Remarkably, the standard enthalpy of activation for solvolysis in 97HFIP is lower for the equatorial than the axial isomer. These results, the role of non-chair conformers for the equatorially substituted isomer, and the nature of the rate-determining step in the limiting SN1 solvolytic mechanism generally are discussed.
Solutions of the 1-methyl-1-cyclohexyl cation 1, by four independent criteria, show unequivocal evidence for a populated equilibrium involving two different "structures" of this cation. One of these criteria makes use of a remarkably large new equilibrium isotope effect, a method that should have general structural use in other carbocation systems. Unfortunately, our previous assignment of a chair and twist-boat conformation for the structures does not accord with the new data. From an analysis of the 13C and 1H NMR shifts and KH/KD isotope effects for 1 and a series of ring-methylated analogues, it can be deduced that both structures are chair conformers and that one structure must involve extensive α-C-H hyperconjugation, while the other structure involves predominantly C-C hyperconjugation. The very existence of this type of isomerism in observable carbocations is unprecedented and has important implications for the field in general.
Derivatives of the two 5-methyladamantan-2-ols and of the two 2,5-dimethyladamantan-2-ols have been submitted to solvolysis conditions, and the products have been analysed. The secondary alcohol derivatives show a preference for the formation of products of retained configuration; in the tertiary derivatives a similar but much weaker tendency is observed. Superimposed on these tendencies is one, similar in magnitude, favouring the formation of products of preferential nucleoPhilic attack from the side syn to the 5-methyl group. These preferences are rationalised.
A full quantum mechanical description of the Menshutkin Reaction has been obtained for gas phase and solution by using density functional theory (DFT) and the self-consistent isodensity polarizable continuum model (SCI-PCM). Ammonia and pyridine are compared as nucleophiles, and methyl chloride and bromide are used as methyl transfer reagents. In the gas phase, all of the reactions proceed via an initial dipole complex, followed by a transition state leading to an ion pair. Methyl bromide shifts the position of the transition state to an earlier position than that found with methyl chloride. In the reaction with methyl chloride, replacing ammonia with pyridine stabilizes the transition state by 3 kcal/mol and stabilizes the ion pair by 17 kcal/mol. In the SCIPCM solvent effect calculations, the dipole complex disappears in both cyclohexane and DMSO. The transition state is shifted to an earlier stage of the reaction and is stabilized with respect to the gas phase. The ion pair product is strongly stabilized, and in DMSO it is calculated to dissociate into free ions. The reactions also were studied using Monte Carlo free energy perturbation. The results were in good agreement with the reaction field calculations. The rates of reaction between pyridine and methyl bromide were determined at 25 °C in cyclohexane, di-n-butyl ether, and acetonitrile and compared with the computational results. Activation free energies calculated using the SCRF-SCIPCM model agree remarkably well with the experimental values.
Much experimental and theoretical work has been directed
toward elucidating the nature of the cationic intermediate(s) involved in cyclopropylcarbinyl, cyclobutyl, and allylcarbinyl interconversions under so-called “stable-ion" as well as solvolytic condition. Whereas all experimental evidence on C_4H_7^+ indicates that the species is a nonclassical cation, controversy continues regarding the equilibrium geometry of this cation, with some favoring the bicyclobutonium structure
la, and others the “bisected” cyclopropylcarbinyl arrangement (1b).
Scaling factors for obtaining fundamental vibrational frequencies, low-frequency vibrations, zero-point vibrational energies (ZPVE), and thermal contributions to enthalpy and entropy from harmonic frequencies determined at 19 levels of theory have been derived through a least-squares approach. Semiempirical methods (AM1 and PM3), conventional uncorrelated and correlated ab initio molecular orbital procedures [Hartree?Fock (HF), M?ller?Plesset (MP2), and quadratic configuration interaction including single and double substitutions (QCISD)], and several variants of density functional theory (DFT:? B-LYP, B-P86, B3-LYP, B3-P86, and B3-PW91) have been examined in conjunction with the 3-21G, 6-31G(d), 6-31+G(d), 6-31G(d,p), 6-311G(d,p), and 6-311G(df,p) basis sets. The scaling factors for the theoretical harmonic vibrational frequencies were determined by a comparison with the corresponding experimental fundamentals utilizing a total of 1066 individual vibrations. Scaling factors suitable for low-frequency vibrations were obtained from least-squares fits of inverse frequencies. ZPVE scaling factors were obtained from a comparison of the computed ZPVEs (derived from theoretically determined harmonic vibrational frequencies) with ZPVEs determined from experimental harmonic frequencies and anharmonicity corrections for a set of 39 molecules. Finally, scaling factors for theoretical frequencies that are applicable for the computation of thermal contributions to enthalpy and entropy have been derived. A complete set of recommended scale factors is presented. The most successful procedures overall are B3-PW91/6-31G(d), B3-LYP/6-31G(d), and HF/6-31G(d).
The hypothesis that the relative energies of anchimerically assisted solvolysis reactions are very similar in the gas phase and in solution, implying that relative carbocation stabilities are the same in both media, is probed in the present work by including solvent effects in the energy computations. We chose water as our solvent since we expect the difference in solvation energies to be large in highly polar media. Results show that the classical 2-norbornyl cation (2) is not significantly more stabilized in aqueous solution than the nonclassical ion (1). Thus both the gas phase ab initio computations and Monte Carlo solution simulation come to the same result. In less polar solvents, the solvation energies are expected to be even more similar. Our results confirm that the nonclassical form 1 of the 2-norbornyl cation is the only stable form in the gas phase and in solution. The classical form 2 is unlikely to be involved in solvolysis reactions. As a consequence, the differences in rates of solvolysis for 2-exo and 2-endo norbornyl derivatives can only be explained in terms of the differences in the exo vs endo transition states. 15 refs., 1 fig.
The potential energy surface of the C4H7+ cation has been investigated with ab initio quantum chemical theory. Extended basis set calculations, including electronic correlation, show that cyclobutyl and cyclopropylcarbinyl cation are equally stable isomers. The saddle point connecting these isomers lies 0.6 kcal/mol above the minima. The global C4H7+ minimum corresponds to the 1-methylallyl cation, which is 9.0 kcal/mol more stable than the cyclobutyl and the cyclopropylcarbinyl cation and 9.5 kcal/mol below the 2-methylallyl cation. These results are in excellent agreement with experimental data.