Allylic strain

Last updated
Allylic strain in an olefin. Generic allylic strain.png
Allylic strain in an olefin.

Allylic strain (also known as A1,3 strain, 1,3-allylic strain, or A-strain) in organic chemistry is a type of strain energy resulting from the interaction between a substituent on one end of an olefin (a synonym for an alkene) with an allylic substituent on the other end. [1] If the substituents (R and R') are large enough in size, they can sterically interfere with each other such that one conformer is greatly favored over the other. [2] Allylic strain was first recognized in the literature in 1965 by Johnson and Malhotra. The authors were investigating cyclohexane conformations including endocyclic and exocylic double bonds when they noticed certain conformations were disfavored due to the geometry constraints caused by the double bond. [3] Organic chemists capitalize on the rigidity resulting from allylic strain for use in asymmetric reactions. [2]

Contents

Quantifying allylic strain energy

The "strain energy" of a molecule is a quantity that is difficult to precisely define, so the meaning of this term can easily vary depending on one's interpretation. [4] Instead, an objective way to view the allylic strain of a molecule is through its conformational equilibrium. Comparing the heats of formation of the involved conformers, an overall ΔHeq can be evaluated. This term gives information about the relative stabilities of the involved conformers and the effect allylic strain has one equilibrium. Heats of formation can be determined experimentally though calorimetric studies; however, calculated enthalpies are more commonly used due to the greater ease of acquisition. [4]

Different methods utizilized to estimate conformational equilibrium enthalpy include: the Westheimer method, [5] the homomorph method, [6] and more simply—using estimated enthalpies of nonbonded interactions within a molecule. [3] Because all of these methods are approximations, reported strain values for the same molecule can vary and should be used only to give a general idea of the strain energy.

Olefins

Calculated rotational energies for different conformations of 3-methyl-1-butene. Allylic 1,3-strain is most prevalent in 1c, making this conformation the highest in energy. 1-butene allylic strain.png
Calculated rotational energies for different conformations of 3-methyl-1-butene. Allylic 1,3-strain is most prevalent in 1c, making this conformation the highest in energy.

The simplest type of molecules which exhibit allylic strain are olefins. Depending on the substituents, olefins maintain varying degrees of allylic strain. In 3-methyl-1-butene, the interactions between the hydrogen and the two methyl groups in the allylic system cause a change in enthalpy equal to 2 kcal/mol. [7] [ verification needed ] As expected, with an increase in substituent size, the equilibrium enthalpies between rotamers also increases. For example, when examining 4-methyl-2-pentene which contains an additional allylic methyl group compared to 3-methyl-1-butene, the enthalpy of rotation for the highest energy conformer increases from 2 kcal/mol to 4 kcal/mol. [7]

Cyclic molecules

Various strain interactions shown in red. (Other hydrogens left off for simplicity) Methylenecyclohexane strain.png
Various strain interactions shown in red. (Other hydrogens left off for simplicity)

Nonbonded 1,3-diaxial interaction energies are commonly used to approximate strain energy in cyclic molecules, as values for these interactions are available. By taking the difference in nonbonded interactions for each conformer, the equilibrium enthalpy can be estimated. The strain energy for methylidenecyclohexane has been calculated to be 4.5 kcalmol−1 using estimations for 1,3-diaxial strain (0.9 kcalmol−1), methyl/hydrogen allylic strain (1.3kcalmol−1), and methyl/methyl allylic strain (7.6 kcalmol−1) values. [2]

The strain energy in 1,8-dimethylnaphthalene was calculated to be 7.6 kcalmol−1 and around 12-15 kcalmol−1 for 4,5-dimethylphenanthrene. [2] Allylic strain tends to be greater for cyclic molecules compared to olefins as strain energy increases with increasing rigidity of the system. An in depth summary of allylic strain in six membered rings has been presented in a review by Johnson, F. [2]

1,8-dimethylnaphthalene and 4,5-dimethylphenanthrene Napthalene phenanthraene methyl-methyl strain.png
1,8-dimethylnaphthalene and 4,5-dimethylphenanthrene

Influencing factors

Several factors influence the energy penalty associated with the allylic strain. In order to relieve strain caused by interaction between the two methyl groups, the cyclohexanes will often exhibit a boat or twist-boat conformation. The boat conformation tends to be the major conformation to the strain. [2] The effect of allylic strain on cis alkenes creates a preference for more linear structures. [1]

Substituent size

The strength of allylic strain increases as the size of the interacting substituents increases. Substituent size and allylic strain.png
The strength of allylic strain increases as the size of the interacting substituents increases.

The size of the substituents interacting at the 1 and 3 positions of an allylic group is often the largest factor contributing to the magnitude of the strain. As a rule, larger substituents will create a larger magnitude of strain. Proximity of bulky groups causes an increase in repulsive Van der Waals forces. This quickly increases the magnitude of the strain. The interactions between the hydrogen and methyl group in the allylic system cause a change in enthalpy equal to 3.6 kcal/mol. [7] The strain energy in this system was calculated to be 7.6 kcal/mol due to interactions between the two methyl groups. [2]

Substituent polarity

Polarity also has an effect on allylic strain. In terms of stereoselectivity, polar groups act like large, bulky groups. Even though two groups may have approximately the same A values the polar group will act as though it were much bulkier. This is due to the donor character of the polar group. Polar groups increase the HOMO energy of the σ-system in the transition state. This causes the transition state to be in a much more favorable position when the polar group is not interacting in a 1,3 allylic strain. [8]

Hydrogen bonding

A represents the conformation that would occur in most situations due to allylic strain. However, as shown in B a hydrogen bond can form that is energetically favorable and cancels the disfavorable allylic strain. Thus, B is the most stable conformation. Allylic strain and hydrogen bonding.png
A represents the conformation that would occur in most situations due to allylic strain. However, as shown in B a hydrogen bond can form that is energetically favorable and cancels the disfavorable allylic strain. Thus, B is the most stable conformation.

With certain polar substituents, hydrogen bonding can occur in the allylic system between the substituents. Rather than the strain that would normally occur in the close group proximity, the hydrogen bond stabilizes the conformation and makes it energetically much more favorable. This scenario occurs when the allylic substituent at the 1 position is a hydrogen bond donor (usually a hydroxyl) and the substituent at the 3 position is a hydrogen bond acceptor (usually an ether). Even in cases where the allylic system could conform to put a much smaller hydrogen in the hydrogen bond acceptor’s position, it is much more favorable to allow the hydrogen bond to form. [9]

Solvents

Solvents also have an effect on allylic strain. When used in conjunction with knowledge of the effects of polarity on allylic strain, solvents can be very useful in directing the conformation of a product that contains an allylic structure in its transition state. When a bulky and polar solvent is able to interact with one of the substituents in the allylic group, the complex of the solvent can energetically force the bulky complex out of the allylic strain in favor of a smaller group. [10]

Conjugation

Conjugation increases the allylic strain because it forces substituents into a configuration that causes their atoms to be in closer proximity, increasing the strength of repulsive Van der Waals forces. [11] This situation occurs most noticeably when carboxylic acid or ketone is involved as a substituent of the allylic group. Resonance effect on the carboxylic group shifts the CO double bond to a hydroxy group. The carboxylic group will thus function as a hydroxyl group that will cause a large allylic strain to form and cancel the stabilization effects of the extended conjugation. This is very common in enolization reactions [2] and can be viewed in the figure below under "Acidic Conditions."

In situations where the molecule can either be in a conjugated system or avoid allylic strain, it has been shown that the molecule's major form will be the one that avoids strain. This has been found via the cyclization in the figure below. [12] Under treatment of perchloric acid, molecule A cyclizes into the conjugated system show in molecule B. However, the molecule will rearrange (due to allylic strain) into molecule C, causing molecule C to be the major species. Thus, the magnitude of destabilization via the allylic strain outweighs the stabilization caused by the conjugated system. [2]

Molecule A undergoes cyclization after treatment with perchloric acid. Due to the allylic strain in molecule B, the molecule was found not to exhibit conjugation stabilization and was stabilized in the formation shown in C. Thus, allylic strain outweighs the stabilization effects of a conjugated system. Allylic strain and conjugation.png
Molecule A undergoes cyclization after treatment with perchloric acid. Due to the allylic strain in molecule B, the molecule was found not to exhibit conjugation stabilization and was stabilized in the formation shown in C. Thus, allylic strain outweighs the stabilization effects of a conjugated system.

Acidic conditions

In cases where an enolization is occurring around an allylic group (usually as part of a cyclic system), A1,3 strain can cause the reaction to be nearly impossible. In these situations, acid treatment would normally cause the alkene to become protonated, moving the double bond to the carboxylic group, changing it to a hydroxy group. The resulting allylic strain between the alcohol and the other group involved in the allylic system is so great that the reaction can not occur under normal thermodynamic conditions. [13] This same enolization occurs much more rapidly under basic conditions, as the carboxylic group is retained in the transition state and allows the molecule to adopt a conformation that does not cause allylic strain. [13]

The keto form (left) cannot undergo enolization under normal acidic conditions, due to the formation of allylic strain (middle). Thus, under normal thermodynamic conditions, the molecule cannot undergo bromation (right). Allylic strain acid catalysis.png
The keto form (left) cannot undergo enolization under normal acidic conditions, due to the formation of allylic strain (middle). Thus, under normal thermodynamic conditions, the molecule cannot undergo bromation (right).

Application of allylic strain in organic reactions and total synthesis

Origin.png

Origin of stereoselectivity of organic reactions from allylic strain

When one is considering allylic strain, one needs to consider the possible conformers and the possible stereoelectronic demand of the reaction. For example, in the conformation of (Z)-4-methylpent-2-ene, the molecule isn't frozen in the favored conformer but rotates in the dihedral angle around 30° at <1kcal/mol cost. In stereoselective reactions, there are 2 effects of allylic strain on the reaction which is the sterics effect and the electronic effects. The sterics effect is where the largest group prefer to be the farthest from the alkene. The electronic effect is where the orbitals of the substituents prefer to align anti or outside of the orbitals depending on the reaction. [14]

Hydroboration 2.png

Hydroboration reaction

The hydroboration reaction is a useful reaction to functionalize alkenes to alcohols. In the reaction the trimethylsilyl (TMS) group fulfill 2 roles in directing the stereoselectivity of the reaction. First, the bulky size of TMS helped the molecule to preferably adopt a conformation where the TMS is not close to the methyl group on the alkene. Second, the TMS group conferred a stereoelectronic effect on the molecule by adopting an anti conformation to the directing orbitals of the alkene. For the regioselectivity of the reaction, the TMS group can stabilize the developing partial positive charge on the secondary carbon a lot better than a methyl group. [15]

Aldol reaction

In the highly versatile and widely used Evans’ Aldol Reaction, [16] allylic strain played a major role in the development of the reaction. The Z enolate was created to avoid the allylic strain with oxazolidinone. The formation of a specific enolate enforces the development of relative stereochemistry throughout the reaction, making the aldol reaction a very predictive and useful methodology out there to synthesize chiral molecules. The absolute stereochemistry is then determined by the chirality of the oxazolidinone.

There is another aspect of aldol reaction that is influenced by the allylic strain. On the second aldol reaction, the product which is a 1,3 dicarbonyl is formed in high diastereoselectivity. This is because the acidity of the proton is significantly reduced because for the deprotonation to occur, it will have to go through a developing allylic strain in the unfavored conformation. In the favored conformation, the proton is not aligned properly for deprotonation to occur.

Aldol6.png
Aldol7.png

Diels-Alder reaction

In an intramolecular Diels-Alder reaction, asymmetric induction can be induced through allylic 1,3 strain on the diene or the dienophile. In the following example, [17] the methyl group on the dienophile forced the molecule to adopt that specific 6-membered ring conformation on the molecule.

DielsAlder3.png

In the model studies to synthesize chlorothricolide, [18] an intramolecular Diels Alder reaction gave a mixture of diastereomers. But by installing the a bulky TMS substituent, the reaction gave the desired product in high diastereoselectivity and regioselectivity in good yield. The bulky TMS substituent helps enhance allylic 1,3 strain in the conformation of the molecule.

DielsAlder.png

Total synthesis of natural products

In the seminar paper on the total synthesis of (+)-monensin, [19] Kishi and co-workers utilized the allylic strain to induce asymmetric induction in the hydroboration oxidation reaction. The reaction is regioselective and stereoselective. The regioselectivity of the reaction is due to the significant positive character developed at the tertiary carbon. The stereoselectivity of the reaction is due to the attack by the borane from the least hindered side to which is where the methyl group lies at.

Monensin.png

Related Research Articles

<span class="mw-page-title-main">Ene reaction</span> Reaction in organic chemistry

In organic chemistry, the ene reaction is a chemical reaction between an alkene with an allylic hydrogen and a compound containing a multiple bond, in order to form a new σ-bond with migration of the ene double bond and 1,5 hydrogen shift. The product is a substituted alkene with the double bond shifted to the allylic position.

The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition. 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. The dipolarophile is typically an alkene or alkyne, but can be other pi systems. When the dipolarophile is an alkyne, aromatic rings are generally produced.

<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.

An allylic rearrangement or allylic shift is an organic reaction in which the double bond in an allyl chemical compound shifts to the next carbon atom. It is encountered in nucleophilic substitution.

<span class="mw-page-title-main">Ring strain</span> Instability in molecules with bonds at unnatural angles

In organic chemistry, ring strain is a type of instability that exists when bonds in a molecule form angles that are abnormal. Strain is most commonly discussed for small rings such as cyclopropanes and cyclobutanes, whose internal angles are substantially smaller than the idealized value of approximately 109°. Because of their high strain, the heat of combustion for these small rings is elevated.

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

Pentane interference or syn-pentane interaction is the steric hindrance that the two terminal methyl groups experience in one of the chemical conformations of n-pentane. The possible conformations are combinations of anti conformations and gauche conformations and are anti-anti, anti-gauche+, gauche+ - gauche+ and gauche+ - gauche− of which the last one is especially energetically unfavorable. In macromolecules such as polyethylene pentane interference occurs between every fifth carbon atom. The 1,3-diaxial interactions of cyclohexane derivatives is a special case of this type of interaction, although there are additional gauche interactions shared between substituents and the ring in that case. A clear example of the syn-pentane interaction is apparent in the diaxial versus diequatorial heats of formation of cis 1,3-dialkyl cyclohexanes. Relative to the diequatorial conformer, the diaxial conformer is 2-3 kcal/mol higher in energy than the value that would be expected based on gauche interactions alone. Pentane interference helps explain molecular geometries in many chemical compounds, product ratios, and purported transition states. One specific type of syn-pentane interaction is known as 1,3 allylic strain or.

<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.

<span class="mw-page-title-main">Cycloheptene</span> Chemical compound

Cycloheptene is a 7-membered cycloalkene with a flash point of −6.7 °C. It is a raw material in organic chemistry and a monomer in polymer synthesis. Cycloheptene can exist as either the cis- or the trans-isomer.

<span class="mw-page-title-main">Ring flip</span> Process in organic chemistry

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">Anomeric effect</span>

In organic chemistry, the anomeric effect or Edward-Lemieux effect 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. This effect was originally observed in pyranose rings by J. T. Edward in 1955 when studying carbohydrate chemistry.

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

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">Asymmetric induction</span> Preferential formation of one chiral isomer over another in a chemical reaction

Asymmetric induction describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment. Asymmetric induction is a key element in asymmetric synthesis.

The Nazarov cyclization reaction is a chemical reaction used in organic chemistry for the synthesis of cyclopentenones. The reaction is typically divided into classical and modern variants, depending on the reagents and substrates employed. It was originally discovered by Ivan Nikolaevich Nazarov (1906–1957) in 1941 while studying the rearrangements of allyl vinyl ketones.

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.

<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.

Macrocyclic stereocontrol refers to the directed outcome of a given intermolecular or intramolecular chemical reaction, generally an organic reaction, that is governed by the conformational or geometrical preference of a carbocyclic or heterocyclic ring, where the ring containing 8 or more atoms.

Rearrangements, especially those that can participate in cascade reactions, such as the aza-Cope rearrangements, are of high practical as well as conceptual importance in organic chemistry, due to their ability to quickly build structural complexity out of simple starting materials. The aza-Cope rearrangements are examples of heteroatom versions of the Cope rearrangement, which is a [3,3]-sigmatropic rearrangement that shifts single and double bonds between two allylic components. In accordance with the Woodward-Hoffman rules, thermal aza-Cope rearrangements proceed suprafacially. Aza-Cope rearrangements are generally classified by the position of the nitrogen in the molecule :

<span class="mw-page-title-main">Epoxidation of allylic alcohols</span>

The epoxidation of allylic alcohols is a class of epoxidation reactions in organic chemistry. One implementation of this reaction is the Sharpless epoxidation. Early work showed that allylic alcohols give facial selectivity when using meta-chloroperoxybenzoic acid (m-CPBA) as an oxidant. This selectivity was reversed when the allylic alcohol was acetylated. This finding leads to the conclusion that hydrogen bonding played a key role in selectivity and the following model was proposed.

References

  1. 1 2 Eric V. Anslyn and Dennis A. Dougherty Modern Physical Organic Chemistry University Science Books, 2006.
  2. 1 2 3 4 5 6 7 8 9 Johnson, F (1968). "Allylic Strain in Six-Membered Rings". Chem. Rev. 68 (4): 375–413. doi:10.1021/cr60254a001.
  3. 1 2 Johnson, F; Malhorta, S K (1965). "Steric Interference in Allylic and Pseudo-Allylic Systems. I. Two Stereochemical Theorems". J. Am. Chem. Soc. 87 (23): 5492–5493. doi:10.1021/ja00951a047.
  4. 1 2 Allinger, N. L.; Hirsch, Jerry A.; Miller, Mary Ann.; Tyminski, Irene J. (1968). "Conformational Analysis. LXIV. Calculation of the Structures and Energies of Unsaturated Hydrocarbons by the Westheimer Method". J. Am. Chem. Soc. 90 (21): 5773–5780. doi:10.1021/ja01023a021.
  5. ↑ Eliel, E. L.; Allinger, N. L.; Angyal, S. J.; Morrison, G. A. Conformational Analysis Interscience Publishers, Inc., New York, N. Y., 1965.
  6. ↑ Brown, H.; Barbarahs, G. K.; Berneis, H. L.; Bonner, W. H.; Johannesen, M. G.; Grayson, M. (1953). "Strained Homomorphs. 14. General Summary". J. Am. Chem. Soc. 75 (1): 1–6. doi:10.1021/ja01097a001.
  7. 1 2 3 4 Hoffman, R (1989). "Allylic 1,3-strain as a controlling factor in stereoselective transformations". Chem. Rev. 89 (8): 1841–1860. doi:10.1021/cr00098a009.
  8. ↑ Bach, T.; Jodicke K.; Kather, K.; Frohlich, R. (1997). "1,3-Allylic Strain as a Control Element in the Paterno-Buchi Reaction of Chiral Silyl Enol Ethers: Synthesis of Diastereomerically Pure Oxetanes Containing Four Contiguous Stereogenic Centers". J. Am. Chem. Soc. 119 (10): 5315–5316. doi:10.1021/ja963827v.
  9. ↑ Ramey, B.; Gardner, P. (1967). "Mechanism of photochemical alcohol addition to alpha, beta-unsaturated ketones". J. Am. Chem. Soc. 89 (15): 3949–3950. doi:10.1021/ja00991a078.
  10. ↑ McGarvey, G.; Williams, J. (1985). "Stereoelectronic controlling features of allylic asymmetry. Application to ester enolate alkylations". J. Am. Chem. Soc. 107 (5): 1435–1437. doi:10.1021/ja00291a067.
  11. ↑ Harris, R. K.; Sheppard, N. (1967). "Comments on the ring inversion of cyclohexane studied by NMR". J. Mol. Spectrosc. 23 (2): 231–235. Bibcode:1967JMoSp..23..231H. doi:10.1016/0022-2852(67)90015-X.
  12. ↑ Overton, K. H.; Renfrew, A. J. (1967). "The configuration at C-13 in labdanolic and eperuic acids". J. Chem. Soc. C : 931–935. doi:10.1039/J39670000931.
  13. 1 2 Vaughn, W R; Caple, R; Csapilla, J; Scheiner, P (1965). "β-Bromo Acids. II. Solvolysis of Cyclic β-Bromo Acids". J. Am. Chem. Soc. 87 (10): 2204. doi:10.1021/ja01088a020.
  14. ↑ Houk K. N.; Paddon-Row, M.; Rondan, N.; Wu, Y.; Brown, F.; Spellmeyer, D.; Metz, J.; Li, Y; Loncharich, R.; et al. (1986). "Theory and Modeling of Stereoselective Organic Reactions". Science . 231 (4742): 1108–1117. Bibcode:1986Sci...231.1108H. doi:10.1126/science.3945819. PMID   3945819.
  15. ↑ Fleming, I. (1988). "Stereocontrol in organic synthesis using silicon compounds". Pure Appl. Chem. 60: 71–78. doi: 10.1351/pac198860010071 .
  16. ↑ Evans, D. A.; Takacs, J. M.; McGee, L. R.; Ennis, M. D.; Mathre, D. J.; Bartroli, J.; et al. (1981). "Chiral enolate design". Pure Appl. Chem. 53 (6): 1109. doi: 10.1351/pac198153061109 . S2CID   93637283.
  17. ↑ Ichihara, A.; et al. (1986). "Stereoselective total synthesis and stereochemistry of diplodiatoxin, a mycotoxin from ?". Tetrahedron Lett. 27 (12): 1347–1350. doi:10.1016/S0040-4039(00)84255-0.
  18. ↑ Roush, W. R.; Kageyama, Masanori; Riva, Renata; Brown, Bradley B.; Warmus, Joseph S.; Moriarty, Kevin J.; et al. (1991). "Enantioselective synthesis of the bottom half of chlorothricolide. 3. Studies of the steric directing group strategy for stereocontrol in intramolecular Diels-Alder reactions". J. Org. Chem. 56 (3): 1192. doi:10.1021/jo00003a049.
  19. ↑ Nicolaou, K. C.; et al. Classics in Total Synthesis. Wiley. p. 185.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.