Anomeric effect

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The a- and b-anomers of D-glucopyranose. A- and b-D-glucopyranose.svg
The α- and β-anomers of D-glucopyranose.

In organic chemistry, the anomeric effect or Edward-Lemieux effect (after J. T. Edward and Raymond Lemieux) is a stereoelectronic effect that describes the tendency of heteroatomic substituents adjacent to a heteroatom within a cyclohexane ring to prefer the axial orientation instead of the less-hindered equatorial orientation that would be expected from steric considerations. [1] This effect was originally observed in pyranose rings by J. T. Edward in 1955 when studying carbohydrate chemistry.

Contents

The term anomeric effect was introduced in 1958. [2] The name comes from the term used to designate the lowest-numbered ring carbon of a pyranose, the anomeric carbon. Isomers that differ only in the configuration at the anomeric carbon are called anomers . The anomers of D-glucopyranose are diastereomers, with the beta anomer having a hydroxyl (−OH) group pointing up equatorially, and the alpha anomer having that (−OH) group pointing down axially.

The anomeric effect can also be generalized to any cyclohexyl or linear system with the general formula C−Y−C−X, where Y is a heteroatom with one or more lone pairs, and X is an electronegative atom or group. [3] The magnitude of the anomeric effect is estimated at 4-8 kJ/mol in the case of sugars, but is different for every molecule.

Methoxyintro.png

In the above case, the methoxy group −O−CH3) on the cyclohexane ring (top) prefers the equatorial position. However, in the tetrahydropyran ring (bottom), the methoxy group prefers the axial position. This is because in the cyclohexane ring, Y = carbon, which is not a heteroatom, so the anomeric effect is not observed and sterics dominates the observed substituent position. In the tetrahydropyran ring, Y = oxygen, which is a heteroatom, so the anomeric effect contributes and stabilizes the observed substituent position. In both cases, X = methoxy group.

The anomeric effect is most often observed when Y = oxygen, but can also be seen with other lone pair bearing heteroatoms in the ring, such as nitrogen, sulfur, and phosphorus. [4] The exact method by which the anomeric effect causes stabilization is a point of controversy, and several hypotheses have been proposed to explain it.

Physical explanation and controversy

The physical reason for the anomeric effect is not completely understood. Several, in part conflicting, explanations have been offered and the topic is still not settled. [5]

Hyperconjugation

Cyclic molecules

A widely accepted explanation is that there is a stabilizing interaction (hyperconjugation) between the unshared electron pair on the endocyclic heteroatom (within the sugar ring) and the σ* orbital of the axial (exocyclic) C–X bond. [6] This causes the molecule to align the donating lone pair of electrons antiperiplanar (180°) to the exocyclic C-X σ bond, lowering the overall energy of the system and causing more stability. [7]

Sigma* Orbital.png

Some authors also question the validity of this hyperconjugation model based on results from the quantum theory of atoms in molecules. [8] While most studies on the anomeric effects have been theoretical in nature, the n–σ* (hyperconjugation) hypothesis has also been extensively criticized on the basis that the electron density redistribution in acetals proposed by this hypothesis is not congruent with the known experimental chemistry of acetals and, in particular, the chemistry of monosaccharides. [9] [10]

Acyclic molecules

Hyperconjugation is also found in acyclic molecules containing heteroatoms, another form of the anomeric effect. If a molecule has an atom with a lone pair of electrons and the adjacent atom is able to accept electrons into the σ* orbital, hyperconjugation occurs, stabilizing the molecule. This forms a "no bond" resonance form. For this orbital overlap to occur, the trans, trans conformation is preferred for most heteroatoms, however for the stabilization to occur in dimethoxymethane, the gauche, gauche conformation is about 3–5 kcal/mol lower in energy (more stable) than the trans,trans conformation—this is about two times as big as the effect in sugars because there are two rotatable bonds (hence it is trans around both bonds or gauche around both) that are affected. [11]

Newman projection linear anomeric effect.png

Dipole minimization

Another accepted explanation for the anomeric effect is the equatorial configuration has the dipoles involving both heteroatoms partially aligned, and therefore repelling each other. [12] By contrast the axial configuration has these dipoles roughly opposing, thus representing a more stable and lower energy state.

THPOH-dipoles.png

Both the hyperconjugation and the dipole minimization contribute to the preferred (Z)-conformation of esters over the (E)-conformation. In the (Z) conformation the lone pair of electrons in the alpha oxygen can donate into the neighboring σ* C-O orbital. In addition, the dipole is minimized in the (Z)-conformation and maximized in the (E)-conformation. [7]

Ester conformers.png

n-n repulsions and C-H hydrogen bonding

If the lone pairs of electrons on the oxygens at the anomeric center of 2-methoxypyran are shown, then a brief examination of the conformations of the anomers reveal that the β-anomer always has at least one pair of eclipsing (coplanar 1,3-interacting) lone pairs, this n-n repulsion is a high energy situation. On the other hand, the α-anomer has conformations in which there are no n-n repulsions, and that is true in the exo-anomeric conformation. The energetically unfavourable n-n repulsion present in the β-anomer, coupled with the energetically favourable hydrogen bond between the axial H-5 and a lone pair of electrons on the axial α-anomeric substituent (C-H/n hydrogen bond), have been suggested [references 7 and 8] to account for most of the energetic difference between the anomers, the anomeric effect. The molecular mechanics program StruMM3D, which is not specially parameterized for the anomeric effect, estimates that the dipolar contributions to the anomeric effect (primarily the n-n repulsion, and C-H hydrogen bonding discussed above) are about 1.5 kcal/mol.

Influences

While the anomeric effect is a general explanation for this type of stabilization for a molecule, the type and amount of stabilization can be affected by the substituents being examined as well as the solvent being studied.

Substituent effect

In a closed system, there is a difference observed in the anomeric effect for different substituents on a cyclohexane or tetrahydropyran ring (Y=Oxygen). When X=OH, the generic anomeric effect can be seen, as previously explained. When X=CN, the same results are seen, where the equatorial position is preferred on the cyclohexane ring, but the axial position is preferred on the tetrahydropyran ring. This is consistent with the anomeric effect stabilization. When X=F, the anomeric effect is in fact observed for both rings. However, when X=NH2, no anomeric effect stabilization is observed and both systems prefer the equatorial position. This is attributed to both sterics and an effect called the reverse anomeric effect (see below). [3]

Solvent effect

One common criticism of the hyperconjugation theory is that it fails to explain why the anomeric effect is not observed when substituted tetrahydropyran molecules are placed in polar solvents, and the equatorial position is once again preferred. It has been shown, however, that hyperconjugation does depend on the solvent in the system. Each of the substituted systems described above were tested in the gas phase (i.e. with no solvent) and in aqueous solution (i.e. polar solvent). When X=F, the anomeric effect was observed in both media, and the axial position was always preferred. This is attributed to hyperconjugation. When X=OH or CN, the anomeric effect was seen in the gas phase, when the axial position was preferred. However, in aqueous solutions, both substituents preferred the equatorial position. This is attributed to the fact that there are more electrostatic repulsions with the axial positioned substituent and the polar solvent, causing the equatorial position to be preferred. When X=NH2, again, no anomeric effect was observed and the equatorial position was always preferred. [13]

Overcoming the anomeric effect

While the anomeric effect can cause stabilization of molecules, it does have a magnitude to its stabilization, and this value can be overcome by other, more destabilizing effects in some cases.

Spirofinal.png

In the example of spiroketals, the orientation on the upper left shows stabilization by the hyperconjugative anomeric effect twice, thus greatly stabilizing the orientation of the molecule. The orientation on the upper right only shows this hyperconjugative anomeric stabilization once, causing it to be the lesser preferred structure. However, when substituent are added onto the spiroketal backbone, the more preferred structure can be changed. When a large substituent is added to the spiroketal backbone, as seen in the lower left, the strain from having this large substituent, R, in the axial position is greatly destabilizing to the molecule. In the molecule on the lower right, R is now in the equatorial position, which no longer causes destabilization on the molecule. Therefore, without substituents, the upper equilibrium reaction is favored on the left hand side, while the lower equilibrium is favored on the right hand side, simply from the addition of a large, destabilizing substituent. [14]

Exo anomeric effect

An extension of the anomeric effect, the exo anomeric effect is the preference of substituents coming off a ring to adopt the gauche conformation, while sterics would suggest an antiperiplanar conformation would be preferred.

Conformations of methoxyTHP.png

An example of this is 2-methoxytetrahydropyran. As the anomeric effect predicts, the methoxy substituent shows an increased preference for the axial conformation. However, there is actually more than one possible axial conformation due to rotation about the C-O bond between the methoxy substituent and the ring. When one applies the principles of the reverse anomeric effect, it can be predicted that the gauche conformer is preferred, suggesting the top left conformation is best in the figure above. This prediction is supported by experimental evidence. Furthermore, this preference for the gauche position is still seen in the equatorial conformation. [15]

Reverse anomeric effect

This term refers to the apparent preference of positively charged nitrogen substituents for the equatorial conformation beyond what normal steric interactions would predict in rings containing an electronegative atom, such as oxygen. Substituents containing carbons with partial positive charges are not seen to exhibit the same effect. [16] Theoretical explanations for the reverse anomeric effect include an electrostatic explanation and the delocalization of the sp3 electrons of the anomeric carbon and oxygen lone pair. [17] There is some debate as to whether or not this is a real phenomenon. The nitrogen containing substituents it has been reported with are quite bulky, making it hard to separate the normal effects of steric bulk and the reverse anomeric effect, if it does exist. [18] For example, in the molecule shown below, the pyridinium substituent strongly prefers the equatorial position, as steric factors would predict, but actually shows a stronger preference for this conformation than predicted, suggesting the reverse anomeric effect is contributing.

Reverseanomeric.png

Metallo-anomeric effect

Late transition metals from groups 10, 11, and 12 when placed at the anomeric carbon show strong axial preferences. [19] This phenomenon termed as the metallo-anomeric effect originates from stabilizing hyperconjugative interactions between oxygen or other heteroatoms with lone pairs and C-M anti-bonding orbitals that act as good acceptors. The generalized metallo-anomeric effect refers to thermodynamic stabilization of synclinal conformers of compounds with the general formula M-CH2-OR. Axial/equatorial preferences can be influenced by ligands attached to the metal and electronic configuration. In general terms, moving from a lighter to a heavier element in the group, the magnitude of the metallo-anomeric effect increases. Furthermore, higher oxidation states favor axial/synclinal conformers.

Synthetic applications

The anomeric effect is taken into consideration synthetically. Due to its discovery in sugars, sugar and carbohydrate chemistry is one of the more common synthetic uses of the anomeric effect. For instance, the Koenigs-Knorr glycosidation installs an α-OR or β-OR group in high diastereoselectivity which is effected by the anomeric effect. Sophorolipid lactone, (+)-Lepicidin A, and (−)-Lithospermoside are a few of the products synthesized via the Koenigs-Knorr Glycosidation overcoming the anomeric effect. [20]

Wikinaturalproducts.png

See also

Related Research Articles

Monosaccharides, also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built.

<span class="mw-page-title-main">Stereoisomerism</span> When molecules have the same atoms and bond structure but differ in 3D orientation

In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in space. This contrasts with structural isomers, which share the same molecular formula, but the bond connections or their order differs. By definition, molecules that are stereoisomers of each other represent the same structural isomer.

<span class="mw-page-title-main">Structural formula</span> Graphic representation of a molecular structure

The structural formula of a chemical compound is a graphic representation of the molecular structure, showing how the atoms are possibly arranged in the real three-dimensional space. The chemical bonding within the molecule is also shown, either explicitly or implicitly. Unlike other chemical formula types, which have a limited number of symbols and are capable of only limited descriptive power, structural formulas provide a more complete geometric representation of the molecular structure. For example, many chemical compounds exist in different isomeric forms, which have different enantiomeric structures but the same molecular formula. There are multiple types of ways to draw these structural formulas such as: Lewis structures, condensed formulas, skeletal formulas, Newman projections, Cyclohexane conformations, Haworth projections, and Fischer projections.

In carbohydrate chemistry, a pair of anomers is a pair of near-identical stereoisomers or diastereomers that differ at only the anomeric carbon, the carbon atom that bears the aldehyde or ketone functional group in the sugar's open-chain form. However, in order for anomers to exist, the sugar must be in its cyclic form, since in open-chain form, the anomeric carbon atom is planar and thus achiral. More formally stated, then, an anomer is an epimer at the hemiacetal/hemiketal carbon atom in a cyclic saccharide. Anomerization is the process of conversion of one anomer to the other. As is typical for stereoisomeric compounds, different anomers have different physical properties, melting points and specific rotations.

<span class="mw-page-title-main">Steric effects</span> Geometric aspects of ions and molecules affecting their shape and reactivity

Steric effects arise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape (conformation) and reactivity of ions and molecules. Steric effects complement electronic effects, which dictate the shape and reactivity of molecules. Steric repulsive forces between overlapping electron clouds result in structured groupings of molecules stabilized by the way that opposites attract and like charges repel.

<span class="mw-page-title-main">Cyclohexane conformation</span> Structures of cyclohexane

Cyclohexane conformations are any of several three-dimensional shapes adopted by molecules of cyclohexane. Because many compounds feature structurally similar six-membered rings, the structure and dynamics of cyclohexane are important prototypes of a wide range of compounds.

<span class="mw-page-title-main">Conformational isomerism</span> Different molecular structures formed only by rotation about single bonds

In chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted just by rotations about formally single bonds. While any two arrangements of atoms in a molecule that differ by rotation about single bonds can be referred to as different conformations, conformations that correspond to local minima on the potential energy surface are specifically called conformational isomers or conformers. Conformations that correspond to local maxima on the energy surface are the transition states between the local-minimum conformational isomers. Rotations about single bonds involve overcoming a rotational energy barrier to interconvert one conformer to another. If the energy barrier is low, there is free rotation and a sample of the compound exists as a rapidly equilibrating mixture of multiple conformers; if the energy barrier is high enough then there is restricted rotation, a molecule may exist for a relatively long time period as a stable rotational isomer or rotamer. When the time scale for interconversion is long enough for isolation of individual rotamers, the isomers are termed atropisomers. The ring-flip of substituted cyclohexanes constitutes another common form of conformational isomerism.

In chemistry, a molecule experiences strain when its chemical structure undergoes some stress which raises its internal energy in comparison to a strain-free reference compound. The internal energy of a molecule consists of all the energy stored within it. A strained molecule has an additional amount of internal energy which an unstrained molecule does not. This extra internal energy, or strain energy, can be likened to a compressed spring. Much like a compressed spring must be held in place to prevent release of its potential energy, a molecule can be held in an energetically unfavorable conformation by the bonds within that molecule. Without the bonds holding the conformation in place, the strain energy would be released.

<span class="mw-page-title-main">Hyperconjugation</span> Concept in organic chemistry

In organic chemistry, hyperconjugation refers to the delocalization of electrons with the participation of bonds of primarily σ-character. Usually, hyperconjugation involves the interaction of the electrons in a sigma (σ) orbital with an adjacent unpopulated non-bonding p or antibonding σ* or π* orbitals to give a pair of extended molecular orbitals. However, sometimes, low-lying antibonding σ* orbitals may also interact with filled orbitals of lone pair character (n) in what is termed negative hyperconjugation. Increased electron delocalization associated with hyperconjugation increases the stability of the system. In particular, the new orbital with bonding character is stabilized, resulting in an overall stabilization of the molecule. Only electrons in bonds that are in the β position can have this sort of direct stabilizing effect — donating from a sigma bond on an atom to an orbital in another atom directly attached to it. However, extended versions of hyperconjugation can be important as well. The Baker–Nathan effect, sometimes used synonymously for hyperconjugation, is a specific application of it to certain chemical reactions or types of structures.

In organic chemistry, a ring flip is the interconversion of cyclic conformers that have equivalent ring shapes that results in the exchange of nonequivalent substituent positions. The overall process generally takes place over several steps, involving coupled rotations about several of the molecule's single bonds, in conjunction with minor deformations of bond angles. Most commonly, the term is used to refer to the interconversion of the two chair conformers of cyclohexane derivatives, which is specifically referred to as a chair flip, although other cycloalkanes and inorganic rings undergo similar processes.

<span class="mw-page-title-main">Gauche effect</span> Molecular-structural phenomenon

In the study of conformational isomerism, the gauche effect is an atypical situation where a gauche conformation is more stable than the anti conformation (180°).

<span class="mw-page-title-main">Carbon–fluorine bond</span> Covalent bond between carbon and fluorine atoms

The carbon–fluorine bond is a polar covalent bond between carbon and fluorine that is a component of all organofluorine compounds. It is one of the strongest single bonds in chemistry, and relatively short, due to its partial ionic character. The bond also strengthens and shortens as more fluorines are added to the same carbon on a chemical compound. As such, fluoroalkanes like tetrafluoromethane are some of the most unreactive organic compounds.

An electric effect influences the structure, reactivity, or properties of a molecule but is neither a traditional bond nor a steric effect. In organic chemistry, the term stereoelectronic effect is also used to emphasize the relation between the electronic structure and the geometry (stereochemistry) of a molecule.

A-values are numerical values used in the determination of the most stable orientation of atoms in a molecule, as well as a general representation of steric bulk. A-values are derived from energy measurements of the different cyclohexane conformations of a monosubstituted cyclohexane chemical. Substituents on a cyclohexane ring prefer to reside in the equatorial position to the axial. The difference in Gibbs free energy (ΔG) between the higher energy conformation and the lower energy conformation is the A-value for that particular substituent.

Carbohydrate conformation refers to the overall three-dimensional structure adopted by a carbohydrate (saccharide) molecule as a result of the through-bond and through-space physical forces it experiences arising from its molecular structure. The physical forces that dictate the three-dimensional shapes of all molecules—here, of all monosaccharide, oligosaccharide, and polysaccharide molecules—are sometimes summarily captured by such terms as "steric interactions" and "stereoelectronic effects".

Carbohydrate NMR spectroscopy is the application of nuclear magnetic resonance (NMR) spectroscopy to structural and conformational analysis of carbohydrates. This method allows the scientists to elucidate structure of monosaccharides, oligosaccharides, polysaccharides, glycoconjugates and other carbohydrate derivatives from synthetic and natural sources. Among structural properties that could be determined by NMR are primary structure, saccharide conformation, stoichiometry of substituents, and ratio of individual saccharides in a mixture. Modern high field NMR instruments used for carbohydrate samples, typically 500 MHz or higher, are able to run a suite of 1D, 2D, and 3D experiments to determine a structure of carbohydrate compounds.

<span class="mw-page-title-main">Oxocarbenium</span>

An oxocarbeniumion is a chemical species characterized by a central sp2-hybridized carbon, an oxygen substituent, and an overall positive charge that is delocalized between the central carbon and oxygen atoms. An oxocarbenium ion is represented by two limiting resonance structures, one in the form of a carbenium ion with the positive charge on carbon and the other in the form of an oxonium species with the formal charge on oxygen. As a resonance hybrid, the true structure falls between the two. Compared to neutral carbonyl compounds like ketones or esters, the carbenium ion form is a larger contributor to the structure. They are common reactive intermediates in the hydrolysis of glycosidic bonds, and are a commonly used strategy for chemical glycosylation. These ions have since been proposed as reactive intermediates in a wide range of chemical transformations, and have been utilized in the total synthesis of several natural products. In addition, they commonly appear in mechanisms of enzyme-catalyzed biosynthesis and hydrolysis of carbohydrates in nature. Anthocyanins are natural flavylium dyes, which are stabilized oxocarbenium compounds. Anthocyanins are responsible for the colors of a wide variety of common flowers such as pansies and edible plants such as eggplant and blueberry.

<span class="mw-page-title-main">Vinyl cation</span> Organic cation

The vinyl cation is a carbocation with the positive charge on an alkene carbon. Its empirical formula is C
2H+
3. More generally, a vinylic cation is any disubstituted carbon, where the carbon bearing the positive charge is part of a double bond and is sp hybridized. In the chemical literature, substituted vinylic cations are often referred to as vinyl cations, and understood to refer to the broad class rather than the C
2H+
3 variant alone. The vinyl cation is one of the main types of reactive intermediates involving a non-tetrahedrally coordinated carbon atom, and is necessary to explain a wide variety of observed reactivity trends. Vinyl cations are observed as reactive intermediates in solvolysis reactions, as well during electrophilic addition to alkynes, for example, through protonation of an alkyne by a strong acid. As expected from its sp hybridization, the vinyl cation prefers a linear geometry. Compounds related to the vinyl cation include allylic carbocations and benzylic carbocations, as well as aryl carbocations.

<span class="mw-page-title-main">Stereoelectronic effect</span> Affect on molecular properties due to spatial arrangement of electron orbitals

In chemistry, primarily organic and computational chemistry, a stereoelectronic effect is an effect on molecular geometry, reactivity, or physical properties due to spatial relationships in the molecules' electronic structure, in particular the interaction between atomic and/or molecular orbitals. Phrased differently, stereoelectronic effects can also be defined as the geometric constraints placed on the ground and/or transition states of molecules that arise from considerations of orbital overlap. Thus, a stereoelectronic effect explains a particular molecular property or reactivity by invoking stabilizing or destabilizing interactions that depend on the relative orientations of electrons in space.

In organic chemistry, the Cieplak effect is a predictive model to rationalize why nucleophiles preferentially add to one face of a carbonyl over another. Proposed by Andrzej Stanislaw Cieplak in 1980, it correctly predicts results that could not be justified by the other standard models at the time, such as the Cram and Felkin–Anh models. In the Cieplak model, electrons from a neighboring bond delocalize into the forming carbon–nucleophile (C–Nuc) bond, lowering the energy of the transition state and accelerating the rate of reaction. Whichever bond can best donate its electrons into the C–Nuc bond determines which face of the carbonyl the nucleophile will add to. The nucleophile may be any of a number of reagents, most commonly organometallic or reducing agents. The Cieplak effect is subtle, and often competes with sterics, solvent effects, counterion complexation of the carbonyl oxygen, and other effects to determine product distribution. Subsequent work has questioned its legitimacy.

References

  1. ↑ IUPAC , Compendium of Chemical Terminology , 2nd ed. (the "Gold Book") (1997). Online corrected version: (1996) " Anomeric Effect ". doi : 10.1351/goldbook.A00372
  2. ↑ Juaristi, E.; Cuevas, G. (1992). "Recent studies of the anomeric effect". Tetrahedron . 48 (24): 5019–5087. doi:10.1016/S0040-4020(01)90118-8.
  3. 1 2 Bauerfeldt, Glauco F.; Cardozo, Thiago M.; Pereira, Márcio S.; da Silva, Clarissa O. (1 January 2013). "The anomeric effect: the dominance of exchange effects in closed-shell systems". Organic & Biomolecular Chemistry. 11 (2): 299–308. doi:10.1039/c2ob26818c. PMID   23172415.
  4. ↑ Kirby, Anthony J. (1983). The anomeric effect and related stereoelectronic effects at oxygen; with 24 tables. Berlin [u.a.]: Springer. ISBN   978-0-387-11684-6.
  5. ↑ "Chemistry World Blog » Anomeric argument". Archived from the original on 2019-05-16. Retrieved 2013-09-13.
  6. ↑ Sundberg, Francis A. Carey; Richard J. (2007). Advanced Organic Chemistry : Part A: Structure and Mechanisms (5. ed.). Berlin: Springer US. p. 229. ISBN   978-0-387-68346-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 Cuevas, Eusebio Juaristi, Gabriel (1995). The anomeric effect. Boca Raton: CRC Press. ISBN   978-0-8493-8941-2.{{cite book}}: CS1 maint: multiple names: authors list (link)
  8. ↑ Vila, A.; Mosquera, R. A. (2007). "Atoms in molecules interpretation of the anomeric effect in the O—C—O unit". J. Comput. Chem. 28 (9): 1516–1530. doi:10.1002/jcc.20585. PMID   17330885. S2CID   19238371.
  9. ↑ Box, V. G. S. (1990). "The role of lone pair interactions in the chemistry of the monosaccharides. The anomeric effect". Heterocycles. 31 (6): 1157–1181. doi: 10.3987/REV-90-414 .
  10. ↑ Box, V. G. S. (1991). "The role of lone pair interactions in the chemistry of the monosaccharides. Stereo-electronic effects in unsaturated monosaccharides". Heterocycles. 32 (4): 795–807. doi: 10.3987/REV-91-425 .
  11. ↑ Sundberg, Francis A. Carey; Richard J. (2007). Advanced Organic Chemistry : Part A: Structure and Mechanisms (5. ed.). Berlin: Springer US. ISBN   978-0-387-68346-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  12. ↑ Sundberg, Francis A. Carey; Richard J. (2007). Advanced Organic Chemistry : Part A: Structure and Mechanisms (5. ed.). Berlin: Springer US. pp. 229–230. ISBN   978-0-387-68346-1.{{cite book}}: CS1 maint: multiple names: authors list (link)
  13. ↑ Freitas, Matheus P. (1 January 2013). "The anomeric effect on the basis of natural bond orbital analysis". Organic & Biomolecular Chemistry. 11 (17): 2885–90. doi:10.1039/c3ob40187a. PMID   23515623.
  14. ↑ Perron, Francoise; Albizati, Kim F. (1 November 1989). "Chemistry of spiroketals". Chemical Reviews. 89 (7): 1617–1661. doi:10.1021/cr00097a015.
  15. ↑ Szarek, Walter A. (1979). Anomeric Effect: Origins and Consequences. Washington: American Chemical Society. ISBN   978-0-8412-0470-6.
  16. ↑ Kirby, A.J. (1983). The Anomeric Effect and Related Stereoelectronic Effects at Oxygen. New York: Springer-Verlag. ISBN   978-0-387-11684-6.
  17. ↑ Perrin, Charles L. (October 1995). "Reverse anomeric effect: fact or fiction?". Tetrahedron. 51 (44): 11901–11935. doi:10.1016/0040-4020(95)00560-u. ISSN   0040-4020.
  18. ↑ Thatcher, Gregory R. J. (1993). The Anomeric Effect and Associated Stereoelectronic Effects. Washington: American Chemical Society. ISBN   978-0-8412-2729-3.
  19. ↑ Zhu, Feng; Walczak, Maciej A. (4 August 2020). "Stereochemistry of Transition Metal Complexes Controlled by the Metallo-Anomeric Effect". Journal of the American Chemical Society. 142 (35): 15127–15136. doi:10.1021/jacs.0c06882. PMC   9622273 . PMID   32786781. S2CID   221121672.
  20. ↑ Kürti, László; Czakó, Barbara (2007). Strategic applications of named reactions in organic synthesis : background and detailed mechanisms; 250 named reactions (Pbk. ed., [Nachdr.]. ed.). Amsterdam [u.a.]: Elsevier Academic Press. ISBN   978-0-12-429785-2.
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