A sigmatropic rearrangement is defined as migration, in an uncatalyzed intramolecular process, of a σ bond, adjacent to one or more π systems, to a new position in a molecule, with the π systems becoming reorganized in the process. Examples are
The order of a sigmatropic rearrangement is expressed by two numbers set in brackets: [i,j].
In the transition state of a sigmatropic rearrangement, the group that migrates is partially bonded to the migration origin and partially bonded to the migration terminus. There are two possible modes for rearrangement. If the migrating group remains on the same face of the system, the rearrangement is suprafacial. If the migrating group moves to the opposite face of the system, the rearrangement is antarafacial.
Sigmatropic rearrangements have cyclic transition states. If the transition state has six or fewer atoms in the ring, rearrangement must be suprafacial because of the geometric constraints of small rings.
The Cope Rearrangment – A [3,3] Sigmatropic Rearrangement
When 1,5-dienes are heated, a [3,3] sigmatropic rearrangement known as the Cope rearrangement occurs to generate an isomeric 1,5-diene. When the diene is symmetrical about the 3,4 bond, the reaction gives a product identical with the starting material:
Therefore, a Cope rearrangement can be detected only when the diene is not symmetrical about this bond. Any 1,5-diene gives the rearrangement; for example, 3-methyl-1,5-hexadiene heated to 300C gives 1,5-heptadiene. However, the reaction takes place more easily (lower temperature required) when there is a group on the 3- or 4-carbon with leads to the new double bond being substituted. The reaction is obviously reversible and produces an equilibrium mixture of the two 1,5-dienes, which is richer in the thermodynamically more stable isomer. However, the equilibrium can be shifted to the right for 3-hydroxy-1,5-dienes, because the product tautomerizes to the ketone or aldehyde:
The reaction of 3-hydroxy-1,5-dienes is called the oxy-Cope rearrangement. It turns out that the reaction is accelerated (by factors of 1010–1017) if the starting alcohol is treated with base (KH is the best) to make the alkoxide. The product is then the potassium enolate, which is more stable than the simple potassium alkoxide starting material, which is hydrolyzed to the ketone. As the reaction proceeds, conjugation is growing between O- and the new π bond. Sulfur substitution also leads to rate enhancement of the oxy-Cope rearrangement.
In amino-Cope rearrangements, the solvent plays a role in the regioselectivity of the reaction. It has been suggested that this latter reaction does not proceed solely by a concerted [3,3] sigmatropic rearrangement.
Cope Reaarangement in Other System
The 1,5-diene system may be inside a ring or part of an allenic system:
but the reaction does not take place when one of the double bonds is part of an aromatic system (e.g., 4-phenyl-1 butene). When the two double bonds are in vinylic groups attached to adjacent ring positions, the product is a ring four carbons larger. This has been applied to divinylcyclopropanes and divinylcyclobutanes:
When heated, 1,5-diynes are converted to 3,4-dimethylenecyclobutenes. A rate-determining Cope rearrangement is followed by a very rapid electrocyclic reaction. The interconversion of 1,3,5-trienes and cyclohexadienes is very similar to the Cope rearrangement.
Like [2 + 2]-cycloadditions, Cope rearrangements of simple 1,5-dienes can be catalyzed by certain transition-metal compounds. For example, the addition of PdCl2(PhCN)2 causes the reaction to take place at room temperature. This can be quite useful synthetically, because of the high temperatures required in the uncatalyzed process.
Not all Cope rearrangements proceed by the cyclic six-centered mechanism. Thus cis-1,2-divinylcyclobutane rearranges smoothly to 1,5-cyclooctadiene, since the geometry is favorable. The trans isomer also gives this product, but the main product is 4-vinylcyclohexene. This reaction can be rationalized as proceeding by a diradical mechanism. although it is possible that at least part of the cyclooctadiene produced comes from a prior epimerization of the trans- to the cis-divinylcyclobutane followed by Cope rearrangement of the latter.
It has been suggested that another type of diradical two-step mechanism may be preferred by some substrates. Indeed, a nonconcerted Cope rearrangement has been reported. In this pathway, the 1,6 bond is formed before the 3,4 bond breaks:
Cope rearrangement of the symmetrical 1,5-hexadiene gives 1,5-hexadiene. This is a degenerate Cope rearrangement. Another molecule that undergoes it is bicyclo[5.1.0]octadiene.
Sigmatropic Rearrangement of Hydrogen
There are two geometrical pathways by which a sigmatropic rearrangement (migration) of hydrogen can take place. For the case of a [1,5]-sigmatropic rearrangement, starting with a substrate, where the migration origin is an asymmetric carbon atom (U ≠ V). In one of the two pathways, the hydrogen moves along the top or bottom face of the π system. This is called suprafacial migration. In the other pathway, the hydrogen moves across the π system, from top to bottom, or vice versa. This is antarafacial migration.
Let us imagine that in the transition state C, the migrating H atom breaks away from the rest of the system, which we may treat as if it were a free radical.
[1,3]- sigmatropic rearrangement of Hydrogen
In a [1,3]-sigmatropic rearrangement, the imaginary transition state consists of a hydrogen atom and an allyl radical. The latter species has three p orbitals, but the only one that concerns us here is the HOMO which, in a thermal rearrangement is D.
The electron of the hydrogen atom is of course in a 1s orbital, which has only one lobe. The rule governing sigmatropic migration of hydrogen is the H must move from a plus to a plus or from a minus to a minus lobe, of the HOMO; it cannot move to a lobe of opposite sign.
The only way this can happen in a thermal [1,3]-sigmatropic rearrangement is if the migration is antarafacial. Consequently, the rule predicts that antarafacial thermal [1,3]-sigmatropic rearrangements are allowed, but the suprafacial pathway is forbidden.
However, in a photochemical reaction, promotion of an electron means that E is now the HOMO; the suprafacial pathway is now allowed and the antarafacial pathway forbidden.
[1,5]- sigmatropic rearrangement of Hydrogen
A similar analysis of [1,5]-sigmatropic rearrangements shows that in this case the thermal reaction must be suprafacial and the photochemical process antarafacial. For the general case, with odd-numbered j, we can say that [1,j]-suprafacial migrations are allowed thermally when j is of the form 4n + 1, and photochemically when j has the form 4n – 1; the opposite is true for antarafacial migrations.
A [1,5]-shift, with six electrons, is allowed thermally only when it is a Huckel system with zero or an even number of sign inversions; hence it requires a suprafacial migration.
Thus a thermal [1,3] migration is allowed to take place only antarafacially, but such a transition state would be extremely strained, and thermal [1,3]-sigmatropic migrations of hydrogen are unknown. On the other hand, the photochemical pathway allows suprafacial [1,3]-shifts, and a few such reactions are known.
The situation is reversed for [1,5]-hydrogen shifts. In this case the thermal rearrangements, being suprafacial, are quite common, while photochemical rearrangements are rare. Two examples of the thermal reaction are
Sigmatropic Rearrangement of Carbon
Sigmatropic migrations of alkyl or aryl groups are less common than the corresponding hydrogen migrations. When they do take place, there is an important difference. Unlike a hydrogen atom, whose electron is in a 1s orbital with only one lobe, a carbon free radical has its odd electron in a p orbital that has two lobes of opposite sign.
We see that in a thermal suprafacial [1,5] process, symmetry can be conserved only if the migrating carbon moves in such a way that the lobe which was originally attached to the p system remains attached to the π system. This can happen only if configuration is retained within the migrating group.
On the other hand, thermal suprafacial [1,3] migration can take place if the migrating carbon switches lobes. If the migrating carbon was originally bonded by its minus lobe, it must now use its plus lobe to form the new C–C bond. Thus, configuration in the migrating group will be inverted.
From these considerations we predict that suprafacial [1,j]-sigmatropic rearrangements in which carbon is the migrating group are always allowed, both thermally and photochemically, but that thermal [1,3] migrations will proceed with inversion and thermal [1,5] migrations with retention of configuration within the migrating group. More generally, we can say that suprafacial [1,j] migrations of carbon in systems where j = 4n – 1 proceed with inversion thermally and retention photochemically, while systems where j = 4n + 1 show the opposite behavior. Where antarafacial migrations take place, all these predictions are of course reversed.
The Claisen Rearrangement – A [3,3] Sigmatropic Rearrangement
Allylic aryl ethers, when heated without solvent, rearrange to o-allylphenols in a reaction called the Claisen rearrangement. This is a one-step mechanism without ionic intermediates or any charges. The second step in the reaction is a simple ionic proton transfer to regenerate aromaticity.
All these reactions are called sigmatropic because a σ bond appears to move from one place to another during the reaction. This particular reaction is called a [3,3]-sigmatropic rearrangement because the new σ bond has a 3,3 relationship to the old σ bond.
The mechanism is a concerted pericyclic [3,3]-sigmatropic rearrangement and accounts for all these facts. For the ortho rearrangement:
Evidence is the lack of a catalyst, the fact that the reaction is first order in the ether, the absence of crossover products when mixtures are heated, and the presence of the allylic shift, which is required by this mechanism. The allylic shift for the ortho rearrangement (and the absence of one for the para) has been demonstrated by 14C labeling, even when no substituents are present.
Para- Claisen Rearrangement
If both ortho positions are filled, the allylic group migrates to the para position. This is often called the para-Claisen rearrangement). There is no reaction when the para and both ortho positions are filled. Migration to the meta position has not been observed. In the ortho migration, the allylic group always undergoes an allylic shift.
On the other hand, in the para migration there is never an allylic shift. The allylic group is found exactly as it was in the original ether. Compounds with propargylic groups (i.e., groups with a triple bond in the appropriate position) do not generally give the corresponding products.
When the ortho positions have no hydrogen, a second [3,3]-sigmatropic migration (a Cope reaction) follows:
and the migrating group is restored to its original structure. The rearrangement of aryl allyl ethers is facilitated by Ag–KI in hot acetic acid, and by AlMe3 in water.
Allylic ethers of enols (allylic vinylic ethers) also undergo the Claisen rearrangement; in fact, it was discovered with these compounds first:
In these cases of course, the final tautomerization does not take place even when R’ = H, since there is no aromaticity to restore, and ketones are more stable than enols. Catalytic Claisen rearrangements of allyl vinyl ethers are well known. The use of water as solvent accelerates the reaction.
Allyl allene ethers undergo a Claisen rearrangement when heated in DMF to give the expected diene with a conjugated aldehyde unit. Allylic esters of β-keto acids undergo a Claisen rearrangement known as the Carroll rearrangement. It is also called the Kimel–Cope rearrangement and the reaction can be catalyzed by a ruthenium complex.