Ei mechanism

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In organic chemistry, the Ei mechanism (Elimination Internal/Intramolecular), also known as a thermal syn elimination or a pericyclic syn elimination, is a special type of elimination reaction in which two vicinal (adjacent) substituents on an alkane framework leave simultaneously via a cyclic transition state to form an alkene in a syn elimination. [1] This type of elimination is unique because it is thermally activated and does not require additional reagents, unlike regular eliminations, which require an acid or base, or would in many cases involve charged intermediates. This reaction mechanism is often found in pyrolysis.

Contents

General features

Compounds that undergo elimination through cyclic transition states upon heating, with no other reagents present, are given the designation as Ei reactions. Depending on the compound, elimination takes place through a four, five, or six-membered transition state. [1] [2]

Cyclic transition states.png

The elimination must be syn and the atoms coplanar for four and five-membered transition states, [3] but coplanarity is not required for six-membered transition states. [1]

Six membered transition state.png

There is a substantial amount of evidence to support the existence of the Ei mechanism such as: 1) the kinetics of the reactions were found to be first order, [4] 2) the use of free-radical inhibitors did not affect the rate of the reactions, indicating no free-radical mechanisms are involved [5] [6] 3) isotope studies for the Cope elimination indicate the C-H and C-N bonds are partially broken in the transition state, [7] this is also supported by computations that show bond lengthening in the transition state [8] and 4) without the intervention of other mechanisms, the Ei mechanism gives exclusively syn elimination products.

There are many factors that affect the product composition of Ei reactions, but typically they follow Hofmann’s rule and lose a β-hydrogen from the least substituted position, giving the alkene that is less substituted (the opposite of Zaitsev's rule). [1] Some factors affecting product composition include steric effects, conjugation, and stability of the forming alkene.

For acyclic substrates, the Z-isomer is typically the minor product due to the destabilizing gauche interaction in the transition state, but the selectivity is not usually high. [2]

Newman projections of cyclic transition states.png

The pyrolysis of N,N-dimethyl-2-phenylcyclohexylamine-N-oxide shows how conformational effects and the stability of the transition state affect product composition for cyclic substrates. [2]

Dimethyl-2-phenylcyclohexylamine-n-oxide.png

In the trans isomer, there are two cis-β-hydrogens that can eliminate. The major product is the alkene that is in conjugation with the phenyl ring, presumably due to the stabilizing effect on the transition state. In the cis isomer, there is only one cis-B-hydrogen that can eliminate, giving the nonconjugated regioisomer as the major product.

Ester (acetate) pyrolysis

The pyrolytic decomposition of esters is an example of a thermal syn elimination. When subjected to temperatures above 400 °C, esters containing β-hydrogens can eliminate a carboxylic acid through a 6-membered transition state, resulting in an alkene. [2] [6]

Ester pyrolysis 1.png

Isotopic labeling was used to confirm that syn elimination occurs during ester pyrolysis in the formation of stilbene. [9]

Ester pyrolysis 2.png

Sulfur-based

Sulfoxide elimination

β-hydroxy phenyl sulfoxides were found to undergo thermal elimination through a 5-membered cyclic transition state, yielding β-keto esters and methyl ketones after tautomerization and a sulfenic acid. [10]

Sulfoxide elim 1.png

Allylic alcohols can be formed from β-hydroxy phenyl sulfoxides that contain a β’-hydrogen through an Ei mechanism, tending to give the β,γ-unsaturation. [11]

Sulfoxide elim 2.png

1,3-Dienes were found to be formed upon the treatment of an allylic alcohol with an aryl sulfide in the presence of triethylamine. [12] Initially, a sulfenate ester is formed followed by a [2,3]-sigmatropic rearrangement to afford an allylic sulfoxide which undergoes thermal syn elimination to yield the 1,3-diene.

Sulfoxide elim 3.png

Chugaev elimination

The Chugaev elimination is the pyrolysis of a xanthate ester, resulting in an olefin. [1] [13] To form the xanthate ester, an alcohol reacts with carbon disulfide in the presence of a base, resulting in a metal xanthate which is trapped with an alkylating agent (typically methyl iodide). The olefin is formed through the thermal syn elimination of the β-hydrogen and xanthate ester. The reaction is irreversible because the resulting by-products, carbonyl sulfide and methanethiol, are very stable.

Chugaev elimination.png

The Chugaev elimination is very similar to the ester pyrolysis, but requires significantly lower temperatures to achieve the elimination, thus making it valuable for rearrangement-prone substrates.

Burgess dehydration reaction

The dehydration of secondary and tertiary alcohols to yield an olefin through a sulfamate ester intermediate is called the Burgess dehydration reaction. [13] [14] [15] The reaction conditions used are typically very mild, giving it some advantage over other dehydration methods for sensitive substrates. This reaction was used during the first total synthesis of taxol to install an exo-methylene group on the C ring. [16]

Burgess dehydration.png

First, the alcohol displaces the triethylamine on the Burgess reagent, forming the sulfamate ester intermediate. β-hydrogen abstraction and elimination of the sulfamate ester through a 6-membered cyclic transition state yields the alkene.

Thiosulfinate elimination

Thiosulfinates can eliminate in the manner analogous to sulfoxides. Representative is the fragmentation of allicin to thioacrolein, which will go on to form vinyldithiins. Such reactions are important in the antioxidant chemistry of garlic and other plants of the genus Allium.

Formation of vinyldithiins from allicin.png

Selenium-based

Selenoxide elimination

The selenoxide elimination has been used in converting ketones, esters, and aldehydes to their α,β-unsaturated derivatives. [1] [17]

Selenoxide elim 1.png

The mechanism for this reaction is analogous to the sulfoxide elimination, which is a thermal syn elimination through a 5-membered cyclic transition state. Selenoxides are preferred for this type of transformation over sulfoxides due to their increased reactivity toward β-elimination, in some cases allowing the elimination to take place at room temperature. [2]

Selenoxide elim 2.png

The areneselenic acid generated after the elimination step is in equilibrium with the diphenyl diselenide which can react with olefins to yield β-hydroxy selenides under acidic or neutral conditions. Under basic conditions, this side reaction is suppressed. [18]

Grieco elimination

The one-pot dehydration of a primary alcohol to give an alkene through an o-nitrophenyl selenoxide intermediate is called the Grieco elimination. [19] [20]

Grieco elimination.png

The reaction begins with the formation of a selenophosphonium salt which reacts with the alcohol to form an oxaphosphonium salt. The aryl selenium anion displaces tributylphosphine oxide forming the alkyl aryl selenide species. The selenide is then treated with excess hydrogen peroxide leading to the selenoxide which eliminates the β-hydrogen through a 5-member cyclic transition state, yielding an alkene.

Grieco elimination mechanism.png

The electron-withdrawing nitro group was found to increase both the rate of elimination and the final yield of the olefin.

Nitrogen-based

Cope elimination

The Cope elimination (Cope reaction) is the elimination of a tertiary amine oxide to yield an alkene and a hydroxylamine through an Ei mechanism. [13] [21] The Cope elimination was used in the synthesis of a mannopyranosylamine mimic. [22] The tertiary amine was oxidized to the amine oxide using m-chloroperoxybenzoic acid (mCPBA) and subjected to high temperatures for thermal syn elimination of the β-hydrogen and amine oxide through a cyclic transition state, yielding the alkene. It is worth noting that the indicated hydrogen (in green) is the only hydrogen available for syn elimination.

Cope elimination.png

Cyclic amine oxides (5, 7-10-membered nitrogen containing rings) can also undergo internal syn elimination to yield acyclic hydroxylamines containing terminal alkenes. [13]

Special cases for the Hofmann elimination

The mechanism for the Hofmann elimination is generally E2, but can go through an Ei pathway under certain circumstances. For some sterically hindered molecules the base deprotonates a methyl group on the amine instead of the β-hydrogen directly, forming an ylide intermediate which eliminates trimethylamine through a 5-membered transition state, forming the alkene. Deuterium labeling studies confirmed this mechanism by observing the formation of deuterated trimethylamine (and no deuterated water, which would form from the E2 mechanism). [23]

Hofmann elimination.png

The Wittig modified Hofmann elimination goes through the same Ei mechanism, but instead of using silver oxide and water as base, the Wittig modification uses strong bases like alkylithiums or KNH2/liquid NH3. [24] [25]

Iodoso elimination

Secondary and tertiary alkyl iodides with strongly electron-withdrawing groups at the α-carbon were found to undergo a pericyclic syn elimination when exposed to m-chloroperbenzoic acid (mCPBA). [26] It is proposed that the reaction goes through an iodoso intermediate before the syn elimination of hypoiodous acid.

Iodoso elimination.png

The scope of this reaction does not include primary alkyl iodides because the iodoso intermediate rearranges to the hypoiodite intermediate, which, under the reaction conditions, is converted to an alcohol. Strongly electron-withdrawing groups suppress the rearrangement pathway, allowing the pericyclic syn elimination pathway to predominate.

Related Research Articles

<span class="mw-page-title-main">Alkene</span> Hydrocarbon compound containing one or more C=C bonds

In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or in the terminal position. Terminal alkenes are also known as α-olefins.

Sharpless asymmetric dihydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol. The reaction has been applied to alkenes of virtually every substitution, often high enantioselectivities are realized, with the chiral outcome controlled by the choice of dihydroquinidine (DHQD) vs dihydroquinine (DHQ) as the ligand. Asymmetric dihydroxylation reactions are also highly site selective, providing products derived from reaction of the most electron-rich double bond in the substrate.

<span class="mw-page-title-main">Elimination reaction</span> Reaction where 2 substituents are removed from a molecule in a 1 or 2 step mechanism

An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one- or two-step mechanism. The one-step mechanism is known as the E2 reaction, and the two-step mechanism is known as the E1 reaction. The numbers refer not to the number of steps in the mechanism, but rather to the kinetics of the reaction: E2 is bimolecular (second-order) while E1 is unimolecular (first-order). In cases where the molecule is able to stabilize an anion but possesses a poor leaving group, a third type of reaction, E1CB, exists. Finally, the pyrolysis of xanthate and acetate esters proceed through an "internal" elimination mechanism, the Ei mechanism.

Hydroboration–oxidation reaction is a two-step hydration reaction that converts an alkene into an alcohol. The process results in the syn addition of a hydrogen and a hydroxyl group where the double bond had been. Hydroboration–oxidation is an anti-Markovnikov reaction, with the hydroxyl group attaching to the less-substituted carbon. The reaction thus provides a more stereospecific and complementary regiochemical alternative to other hydration reactions such as acid-catalyzed addition and the oxymercuration–reduction process. The reaction was first reported by Herbert C. Brown in the late 1950s and it was recognized in his receiving the Nobel Prize in Chemistry in 1979.

<span class="mw-page-title-main">Cope reaction</span> Reaction of N-oxide to alkene and hydroxylamine

The Cope reaction or Cope elimination, developed by Arthur C. Cope, is the elimination reaction of an N-oxide to an alkene and a hydroxylamine.

The Heck reaction is the chemical reaction of an unsaturated halide with an alkene in the presence of a base and a palladium catalyst to form a substituted alkene. It is named after Tsutomu Mizoroki and Richard F. Heck. Heck was awarded the 2010 Nobel Prize in Chemistry, which he shared with Ei-ichi Negishi and Akira Suzuki, for the discovery and development of this reaction. This reaction was the first example of a carbon-carbon bond-forming reaction that followed a Pd(0)/Pd(II) catalytic cycle, the same catalytic cycle that is seen in other Pd(0)-catalyzed cross-coupling reactions. The Heck reaction is a way to substitute alkenes.

<span class="mw-page-title-main">Michaelis–Arbuzov reaction</span> Chemical reaction

The Michaelis–Arbuzov reaction is the chemical reaction of a trivalent phosphorus ester with an alkyl halide to form a pentavalent phosphorus species and another alkyl halide. The picture below shows the most common types of substrates undergoing the Arbuzov reaction; phosphite esters (1) react to form phosphonates (2), phosphonites (3) react to form phosphinates (4) and phosphinites (5) react to form phosphine oxides (6).

<span class="mw-page-title-main">Organoboron chemistry</span> Study of compounds containing a boron-carbon bond

Organoboron chemistry or organoborane chemistry studies organoboron compounds, also called organoboranes. These chemical compounds combine boron and carbon; typically, they are organic derivatives of borane (BH3), as in the trialkyl boranes.

β-Hydride elimination

β-Hydride elimination is a reaction in which a metal-alkyl centre is converted into the corresponding metal-hydride-alkene. β-Hydride elimination can also occur for many alkoxide complexes as well. The main requirements are that the alkyl group possess a C-H bond β to the metal and that the metal be coordinatively unsaturated. Thus, metal-butyl complexes are susceptible to this reaction whereas metal-methyl complexes are not. The complex must have an empty site cis to the alkyl group for this reaction to occur. β-Hydride elimination, which can be desirable or undesirable, affects the behavior of many organometallic complexes.

In organic chemistry, hydroboration refers to the addition of a hydrogen-boron bond to certain double and triple bonds involving carbon. This chemical reaction is useful in the organic synthesis of organic compounds.

Dihydroxylation is the process by which an alkene is converted into a vicinal diol. Although there are many routes to accomplish this oxidation, the most common and direct processes use a high-oxidation-state transition metal. The metal is often used as a catalyst, with some other stoichiometric oxidant present. In addition, other transition metals and non-transition metal methods have been developed and used to catalyze the reaction.

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

The Chugaev elimination is a chemical reaction that involves the elimination of water from alcohols to produce alkenes. The intermediate is a xanthate. It is named for its discoverer, the Russian chemist Lev Aleksandrovich Chugaev (1873–1922), who first reported the reaction sequence in 1899.

The Kulinkovich reaction describes the organic synthesis of substituted cyclopropanols through reaction of esters with dialkyl­dialkoxy­titanium reagents, which are generated in situ from Grignard reagents containing a hydrogen in beta-position and titanium(IV) alkoxides such as titanium isopropoxide. This reaction was first reported by Oleg Kulinkovich and coworkers in 1989.

In organometallic chemistry, a migratory insertion is a type of reaction wherein two ligands on a metal complex combine. It is a subset of reactions that very closely resembles the insertion reactions, and both are differentiated by the mechanism that leads to the resulting stereochemistry of the products. However, often the two are used interchangeably because the mechanism is sometimes unknown. Therefore, migratory insertion reactions or insertion reactions, for short, are defined not by the mechanism but by the overall regiochemistry wherein one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:

Selenoxide elimination is a method for the chemical synthesis of alkenes from selenoxides. It is most commonly used to synthesize α,β-unsaturated carbonyl compounds from the corresponding saturated analogues. It is mechanistically related to the Cope reaction.

<span class="mw-page-title-main">Reductions with samarium(II) iodide</span>

Reductions with samarium(II) iodide involve the conversion of various classes of organic compounds into reduced products through the action of samarium(II) iodide, a mild one-electron reducing agent.

An insertion reaction is a chemical reaction where one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:

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

The White catalyst is a transition metal coordination complex named after the chemist by whom it was first synthesized, M. Christina White, a professor at the University of Illinois. The catalyst has been used in a variety of allylic C-H functionalization reactions of α-olefins. In addition, it has been shown to catalyze oxidative Heck reactions.

<span class="mw-page-title-main">Sulfinyl halide</span> Class of chemical compounds

Sulfinyl halide have the general formula R−S(O)−X, where X is a halogen. They are intermediate in oxidation level between sulfenyl halides, R−S−X, and sulfonyl halides, R−SO2−X. The best known examples are sulfinyl chlorides, thermolabile, moisture-sensitive compounds, which are useful intermediates for preparation of other sufinyl derivatives such as sulfinamides, sulfinates, sulfoxides, and thiosulfinates. Unlike the sulfur atom in sulfonyl halides and sulfenyl halides, the sulfur atom in sulfinyl halides is chiral, as shown for methanesulfinyl chloride.

In organic chemistry, the Davis oxidation or Davis' oxaziridine oxidation refers to oxidations involving the use of the Davis reagent or other similar oxaziridine reagents. This reaction mainly refers to the generation of α-hydroxy carbonyl compounds (acyloins) from ketones or esters. The reaction is carried out in a basic environment to generate the corresponding enolate from the ketone or ester. This reaction has been shown to work for amides.

References

  1. 1 2 3 4 5 6 March, Jerry (2007). Advanced Organic Chemistry (6th ed.). New York: Wiley. ISBN   0471720917.
  2. 1 2 3 4 5 Carey, F. A.; Sunburg, R. J. Advanced Organic Chemistry: Reaction and Synthesis, 5th Ed.; Part B; Springer: New York, 2010
  3. ↑ Branko, J. (1997). "Theoretical studies of thermal syn elimination reaction of organic amine oxide, sulfoxide and phosphoxide by ab initio and density functional methods". Theo. Chem.389 257-263.
  4. ↑ O’Connor, G.L.; Nace, H. R. (1953). "Further Studies on the Chugaev Reaction and Related Reactions". J. Am. Chem. Soc.75 2118-.
  5. ↑ Barton, D.H.R.; Head, A.J.; Williams, R.J. (1953). "Stereospecificity in Thermal Elimination Reactions. Part III. The Pyrolysis of (−)-Menthyl Benzoate". J. Chem Soc.453 1715- .
  6. 1 2 Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic Chemistry, Murdzek, J., Ed. University Science Books, 2006.
  7. ↑ Wright, D.R.; Sims, L.B.; Fry, A. (1983). "Carbon-14 kinetic isotope effects and kinetic studies in the syn-elimination reactions of (2-phenylethyl)dimethylamine oxides". J. Am. Chem. Soc.105 3714-.
  8. ↑ Kahn, S.D; Erickson, J.A. (1994). "Theoretical Studies of Thermal Syn Elimination Reactions. The Relative Rates of Ethyl Formate, Ethyl Xanthate, and Ethyl Phosphinate Eliminations". J. Am. Chem. Soc.116 6271-6276.
  9. ↑ Curtin, D.Y.; Kellom, D.B. (1953). "Elimination and Replacement Reactions of dl-erythro- and dl-threo-2-Deutero-1,2-diphenylethanol and Derivatives". J. Am. Chem. Soc.75 6011-.
  10. ↑ Kinoshita, M.; Kunieda, N.; Nokami, J. (1975). "Pyrolysis of B-Hydroxy Sulfoxides to Ketones". Tetrahedron Lett.33 2841-2844.
  11. ↑ OKawara, R.; Ueta, K.; Nokami, J. (1978). "Pyrolysis of B-Hydroxy Sulfoxides II. Synthesis of Allylic alcohols". Tetrahedron Lett.49 4903-4904.
  12. ↑ Wollowitz, S.; Reich, H.J. (1982). "Conversion of Allyl Alcohols to 1,3-Dienes by Sequential Sulfenate-Sulfoxide [2,3] Sigmatropic Rearrangement and Syn Elimination". J. Am. Chem. Soc.104 7051-7059.
  13. 1 2 3 4 Kurti, L.; Czako, B. Strategic Applications of Named Reactions in Organic Synthesis, Academic Press, 2005.
  14. ↑ Taylor, E.A.; Penton, H.R.Jr.; Burgess, E.M. (1970). "Synthetic Applications of N-Carboalkoxysulfamate Esters". J. Am. Chem. Soc.92 5224-5226.
  15. ↑ Taylor, E.A.; Penton, H.R.Jr.; Burgess, E.M. (1973). "Thermal Reactions of Alkyl N-Carbomethoxysulfamate Esters". J. Org. Chem.38 26-.
  16. ↑ Holton, R.A.; et al. (1994). "First Total Synthesis of Taxol. 2. Completion of the C and D Rings". J. Am. Chem. Soc.116 1599-1600.
  17. ↑ Lauer, R.F; Young, M.W.; Sharpless, K.B. (1973). "Reactions of Selenoxides: Thermal Syn elimination and H2O-18 Exchange". Tetrahedron Lett.22 1979-1982.
  18. ↑ Reich, H.J.; Wollowitz, S.; Trend, J.E.; Chow, F.; Wendelborn, D.F. (1978). "Syn Elimination of Alkyl Selenoxides. Side Reactions Involving Selenenic Acids. Structural and Solvent Effects on Rates". J. Org. Chem.43 1697-.
  19. ↑ Grieco, P.A.; Gilman, S.; Nishizawa, M. (1976). "Organoselenium Chemistry. A Facile One-Step Synthesis of Alkyl Aryl Selenides from Alcohols". J. Org. Chem.41 1485-.
  20. ↑ Young, M.W.; Sharpless, B.K. (1975). "Olefin Synthesis. Rate Enhancement of the Elimination of Alkyl Aryl Selenoxides by Electron-Withdrawing Substituents". J. Org. Chem.40 947-.
  21. ↑ Cope, A.C.; Foster, T.T.; Towle, P.H. (1949). "Thermal Decomposition of Amine Oxides to Olefins and Dialkylhydroxylamines". J. Am. Chem. Soc.71 3929-.
  22. ↑ Vasella, A.; Remen, L. (2002). "Conformationally Biased Mimics of Mannopyranosylamines: Inhibitors of B-Mannosidases?". Helv. Chim. Acta.85 1118-.
  23. ↑ Cope, A.C.; Mehta, A.S. (1963). "Mechanism of the Hofmann Elimination Reaction: An Ylide Intermediate in the Pyrolysis of a Highly Branched Quaternary Hydroxide". J. Am. Chem. Soc.85 1949-.
  24. ↑ Wittig, G.; Polster, R. (1957). Ann. Chem.102 612-.
  25. ↑ Bach, R.D.; Bair, K.W.; Andrzejewski, D. (1972). "The Wittig Modification of the Hofmann Elimination Reaction. Evidence for an alpha’, beta Mechanism". J. Am. Chem. Soc.94 8608-.
  26. ↑ Reich, H. J., Peake, S. L. (1978). “Hypervalent Organoiodine Chemistry. Syn Elimination of Alkyl Iodoso Compounds”. J. Am. Chem. Soc.100 4888-.
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