Sigmatropic reaction

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A sigmatropic reaction in organic chemistry is a pericyclic reaction. A sigmatropic reaction does not use a catalyst and involves a single molecule (an uncatalyzed intramolecular process). It changes one σ-bond into a different σ-bond.[1] The name sigmatropic is the result of a compounding of the long-established "sigma" name for single carbon-carbon bonds and the Greek word tropos, meaning turn. This is a rearrangement reaction which means that the bonds in a molecule shift between atoms without any atoms leaving or new atoms added to the molecule. In a sigmatropic reaction, a substituent moves from one part of a π-bonded system to another part in an intramolecular reaction with simultaneous rearrangement of the π system. True sigmatropic reactions usually do not need a catalyst. Some sigmatropic reactions are catalyzed by a Lewis acid. Sigmatropic reactions often have transition-metal catalysts that form intermediates in analogous reactions. The most well-known of the sigmatropic rearrangements are the [3,3] Cope rearrangement, Claisen rearrangement, Carroll rearrangement and the Fischer indole synthesis.

Overview of Sigmatropic Shifts[change | change source]

Woodward-Hoffman Sigmatropic Shift Nomenclature[change | change source]

A special notation is used to describe sigmatropic shifts. Each of the carbon atoms on the backbone of the molecule are assigned a position number. Sigmatropic rearrangements are described by an order term [i,j]. This means the migration of a σ-bond adjacent to one or more π systems to a new position (i-1) and (j-1) atoms removed from the original location of the σ-bond.[2] When the sum of i and j is an even number, this is an indication of the involvement of a neutral, all C atom chain. An odd number suggests that there is a charged C atom or of a heteroatom lone pair replacing a carbon-carbon double bond. Thus, [1,5] and [3,3] shifts become [1,4] and [2,3] shifts with heteroatoms, while preserving symmetry considerations. Hydrogens are omitted in the third example for clarity.

Woodward hoffmann order nomenclature detailed 2.png

Here is a way to find the order of a given sigmatropic rearrangement. The first step is to give numbers to each atom starting with the atoms of the bond being broken as atom 1. Chemists count the atoms in each direction from the broken bond to the atoms that form the new σ-bond in the product. The numbers that correspond to the atoms forming the new bond are then separated by a comma and placed within brackets. This creates the sigmatropic reaction order descriptor.[3]

Woodward hoffmann order nomenclature bond break.png

Chemists also count atoms when naming a sigmatropic shift where a hydrogen atom moves. The carbon chain does not break in a hydrogen atom migration. So, chemists count across all atoms involved in the reaction rather than only across the closest atoms. For example, the following hydrogen atom migration is of order [1,5], attained by counting counterclockwise through the π system, rather than the [1,3] order through the ring CH2 group that would mistakenly result if counted clockwise.

Woodward hoffmann order nomenclature hydrogen -1,5-.png

Suprafacial and Antarafacial Shifts[change | change source]

Chemists have studied sigmatropic reactions where the migrating group has a sterocenter. In principle, all sigmatropic shifts can occur with either the same (retention) or the opposite (inversion) geometry of the migrating group. This depends on whether the original bonding lobe of the migrating atom or its other lobe is used to form the new bond.[3]

Stereochemistry rentention inversion.png

In cases of stereochemical retention, the migrating group translates without rotation into the bonding position. In the case of stereochemical inversion the migrating group both rotates and translates to reach its bonded conformation.

There is another way that a sigmatropic reaction can produce products with different sterochemistry. The migrating group can stay on the original face of the π system after rebonding. Or, it can go to the opposite face of the π system. If the migrating group remains on the same face of the π system, the shift is known as suprafacial. If the migrating group transfers to the opposite face is called an antarafacial shift.[2] Transformations that occur within small- or medium-sized rings cannot make antarafacial shifts.

Suprafacial antarafacial -1,5-.png

Classes of Sigmatropic Rearrangements[change | change source]

[1,3] Shifts[change | change source]

Thermal Hydride Shifts[change | change source]

In a thermal [1,3] hydride shift, a hydride moves three atoms. The Woodward-Hoffmann rules dictate that it would proceed in an antarafacial shift. Although such a shift is symmetry allowed, the Mobius topology required in the transition state prohibits such a shift. It is geometrically impossible. This is why enols do not isomerize without an acid or base catalyst.[3]

Impossible Shift

Thermal Alkyl Shifts[change | change source]

Thermal alkyl [1,3] shifts, similar to [1,3] hydride shifts, must proceed antarafacially. The geometry of the transition state is prohibitive. But an alkyl group, due to the nature of its orbitals, can invert its geometry and form a new bond with the back lobe of its sp3 orbital. This reaction will result a suprafacial shift. These reactions are still not common in open chain systems because of the highly ordered nature of the transition state. So, the reactions work better in cyclic molecules.[3]

[1,3] Alkyl Shifts

Photochemical [1,3] Shifts[change | change source]

Photochemical [1,3] shifts should be suprafacial shifts; however, most are non-concerted because they proceed through a triplet state (that is, they have a diradical mechanism, to which the Woodward-Hoffmann rules do not apply).[3]

[1,5] Shifts[change | change source]

A [1,5] shift involves the shift of 1 substituent (-H, -R or -Ar) down 5 atoms of a π system. Hydrogen has been shown to shift in both cyclic and open chain systems at temperatures at or above 200 ˚C.[3] These reactions are predicted to proceed suprafacially, by a Huckel-topology transition state.

[1,5] Hydride shift in a cyclic system

Photoirradiation would require an antarafacial shift of hydrogen. Although such reactions are rare, there are examples where antarafacial shifts are favored:[4]

Antarafacial [1,5] Hydride Shift

In contrast to hydrogen [1,5] shifts, there have never been any observed [1,5] alky shifts in an open-chain system.[3] Chemists have determined rate preferences for [1,5] alkyl shifts in cyclic systems: carbonyl and carboxyl> hydride> phenyl and vinyl>> alkyl.[5][6]

Alkyl groups undergo [1,5] shifts very poorly and usually require high temperatures. However, for cyclohexadienes, the temperature for alkyl shifts is not much higher than that for carbonyls, the best migratory group. A study showed that this is because alkyl shifts on cyclohexadienes proceed through a different mechanism. First the ring opens, followed by a [1,7] shift, and then the ring reforms electrocyclically:[7]

alkyl shift on cyclohexadiene

This same mechanistic process is seen below, without the final electrocyclic ring-closing reaction, in the interconversion of lumisterol to vitamin D2.

[1,7] Shifts[change | change source]

[1,7] sigmatropic shifts are predicted by the Woodward-Hoffmann rules to proceed in an antarafacial fashion, by a Mobius topology transition state. An antarafacial [1,7] shift is observed in the conversion of lumisterol to vitamin D2, where following an electrocyclic ring opening to previtamin D2, a methyl hydrogen shifts.[8]

conversion of lumisterol to vitamin D

Bicyclic nonatrienes also undergo [1,7] shifts in a so called walk rearrangement,[9] which is the shift of divalent group, as part of a three-membered ring, in a bicyclic molecule.

walk rearrangement of bicycle nonatriene

[3,3] Shifts[change | change source]

[3,3] sigmatropic shifts are well studied sigmatropic rearrangements. The Woodward-Hoffman rules predict that these six electron reactions would proceed suprafacially, using a Huckel topology transition state.

Claisen Rearrangement[change | change source]

Discovered in 1912 by Rainer Ludwig Claisen, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.[10][11][12] This rearrangement is a useful carbon-carbon bond-forming reaction. An example of Claisen rearrangement is the [3,3] rearrangement of an allyl vinyl ether, which upon heating yields a γ,δ-unsaturated carbonyl. The formation of a carbonyl group makes this reaction, unlike other sigmatropic rearrangements, inherently irreversible.

The Claisen rearrangement
Aromatic Claisen rearrangement[change | change source]

The ortho-Claisen rearrangement involves the [3,3] shift of an allyl phenyl ether to an intermediate which quickly tautomerizes to an ortho-substituted phenol.

Aromatic Claisen Rearrangement

When both the ortho positions on the benzene ring are blocked, a second ortho-Claisen rearrangement will occur. This para-Claisen rearrangement ends with the tautomerization to a tri-substituted phenol.

Para-Claisen Rearrangement

Cope Rearrangement[change | change source]

The Cope rearrangement is an extensively studied organic reaction involving the [3,3] sigmatropic rearrangement of 1,5-dienes.[13][14][15] It was developed by Arthur C. Cope. For example 3,4-dimethyl-1,5-hexadiene heated to 300 °C yields 2,6-octadiene.

The Cope rearrangement of 3,4-dimethyl-1,5-hexadiene
Oxy-Cope rearrangement[change | change source]

The Oxy-Cope rearrangement a hydroxyl group is added at C3 forming an enal or enone after Keto-enol tautomerism of the intermediate enol:[16]

Oxy-Cope rearrangement

Carroll Rearrangement[change | change source]

The Carroll rearrangement is a rearrangement reaction in organic chemistry and involves the transformation of a β-keto allyl ester into a α-allyl-β-ketocarboxylic acid.[17] This organic reaction can be followed by decarboxylation and the final product is a γ,δ-allylketone. The Carroll rearrangement is an adaptation of the Claisen rearrangement and effectively a decarboxylative allylation.

Carroll Rearrangement

Fischer Indole Synthesis[change | change source]

The Fischer indole synthesis is a chemical reaction that produces the aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic conditions.[18][19] The reaction was discovered in 1883 by Hermann Emil Fischer.

The Fischer indole synthesis

The choice of acid catalyst is very important. Successful acid catalysts include: Bronsted acids such as HCl, H2SO4, polyphosphoric acid and p-toluenesulfonic acid. Lewis acids such as boron trifluoride, zinc chloride, iron chloride, and aluminium chloride are also useful catalysts.

Several reviews have been published.[20][21][22]

[5,5] Shifts[change | change source]

Similar to [3,3] shifts, the Woodward-Hoffman rules predict that [5,5] sigmatropic shifts would proceed suprafacially, Huckel topology transition state. These reactions are rarer than [3,3] sigmatropic shifts, but this is mainly a function of the fact that molecules that can undergo [5,5] shifts are rarer than molecules that can undergo [3,3] shifts.[3]

[5,5] shift of phenyl pentadienyl ether

Walk Rearrangements[change | change source]

The migration of a divalent group, such as O, S, NR or CR2, which is part of a three-membered ring in a bicyclic molecule, is commonly referred to as a walk rearrangement. This can be formally characterized according to the Woodward-Hofmann rules as being a (1, n) sigmatropic shift.[23] An example of such a rearrangement is the shift of substituents on tropilidenes (1,3,5-cycloheptatrienes). When heated, the pi-system goes through an electrocyclic ring closing to form bicycle[4,1,0]heptadiene (norcaradiene). Thereafter follows a [1,5] alkyl shift and an electrocyclic ring opening.

norcaradiene rearrangement

Proceeding through a [1,5] shift, the walk rearrangement of norcaradienes is expected to proceed suprafacially with a retention of stereochemistry. Experimental observations, however, show that the 1,5-shifts of norcaradienes proceed antarafacially.[24] Theoretical calculations found the [1,5] shift to be a diradical process, but without involving any diradical minima on the potential energy surface.[25]

Related pages[change | change source]

References[change | change source]

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  2. 2.0 2.1 Woodward, R.B.; Hoffmann, R. The Conservation of Orbital Symmetry. Verlag Chemie Academic Press. 2004. ISBN 0-89573-109-6.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Miller, Bernard. Advanced Organic Chemistry. 2nd Ed. Upper Saddle River: Pearson Prentice Hall. 2004. ISBN 0-13-065588-0
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