Wittig and Stevens Rearrangement Three examples of an unusual 1,2 alkyl shift from oxygen to carbon, known as the [1,2]-Wittig rearrangement, are shown below. Here a powerful base generates a reactive carbanion alpha to an ether.
An intramolecular shift of an alkyl or aryl group then creates a much more stable alkoxide anion, which in the last example eliminates cyanide anion. Many studies of the mechanism of this rearrangement have been conducted, and it has been established to be intramolecular.
The initially created negative charge weakens the other carbon-oxygen bond, enabling a rapid radical-radical anion dissociation-recombination process to take place green-shaded box.
A related reaction involving a 1,2-shift from nitrogen to carbon is known as the Stevens rearrangement. Many aspects of this transformation are similar to the Wittig rearrangement. Clicking on the above diagram will display examples of the Stevens rearrangement.
Other Sigmatropic Shifts Base catalyzed reactions of allylic ethers and amines may take different paths depending on substitution and conditions. Often [2,3]-sigmatropic shifts occur in preference to others. The example shown below is illustrative. Both the [2,3]-shift and the minor [1,4]-shift are regio and stereospecific, suggesting a structured transition state for each.
A general example involving diallyl ethers is shown in the following diagram. By clicking on the diagram the cyclic chair-like mechanism proposed to account for the stereospecificity of this reaction will be displayed. A second click on the diagram will show two additional examples which demonstrate the synthetic utility of the reaction. Shifts Occurring by Addition-Elimination Mechanisms. The Sommelet-Hauser rearrangement, a reaction that often competes with the Stevens rearrangement, might be classified as a [2,3]-sigmatropic shift.
However, it may also be considered an addition-elimination process, as drawn below. A nitrogen ylide, formed by reaction of a quaternary ammonium salt with strong base, is the reactive intermediate.
This species may be trapped by an electrophile, but normally rearranges in the fashion shown. The Truce-Smiles rearrangement displayed by clicking on the diagram represents another such aryl relocation, in this case a 1,4-shift. As depicted in the following diagram, this reaction is believed to proceed by way of a cyclopropanone intermediate. Facile conversion of cyclopropanones to hydrates and hemiacetals relief of angle strain occurs, and the cyclopropoxide conjugate base undergoes ring opening and solvent protonation.
In the case of unsymmetrical cyclopropanones the ring cleavage takes place on the side that yields the more stable carbanion or leads to elimination of a stable anion second example.
A debate concerning the nature of the carbon-carbon bond formation step now favors direct synchronous formation of the cyclopropanone by a 1,3-elimination, as shown, rather than initial ionization of the enolate to a zwitterionic species such as that drawn in the green box. However, in polar solvents this intermediate may play a role. By clicking on the above diagram another example of the Favorskii rearrangement will be displayed. When stereoisomeric substrates were examined, the rearrangement proved to be stereospecific, ruling out a common zwitterionic intermediate.
The examples in the green-shaded area clearly demonstrate inversion of configuration in the carbon-carbon bond forming step. An application of the Favorskii rearrangement in synthesis will be shown above by clicking on the diagram a second time.
The Payne Rearrangement Epoxy alcohols undergo reversible intramolecular epoxide opening reactions known as the Payne rearrangement. The following diagram illustrates three such reactions, and a general mechanism is written in the gray-shaded box. The equilibrium usually favors the more highly substituted epoxide moiety. As expected for an SN2, process, these transformations are stereospecific.
Although such equilibria may not always lie in the desired direction, subsequent reaction may divert one of the components to a useful product. An example will be shown by clicking on the diagram. Even though the terminal epoxide is a minor component of the Payne equilibrium, its kinetic advantage in the ring opening step determines the final product. The course of reaction in the absence of the Payne rearrangement is displayed in the gray-shaded box. Grob Fragmentation An interesting and generally useful skeletal transformation, involving specific carbon-carbon bond cleavage with accompanying conversion of certain sigma-bonds to pi-bonds, is known as the Grob fragmentation.
As background for discussing this reaction, it is helpful to define the concept of ethylogy, which may be regarded as the sigma-bond equivalent of vinylogy. This is illustrated in the following diagram. Here a simple nucleophilic fragmentation at M is converted to an ethylagous analog by the insertion of a two carbon ethyl segment between the reacting moieties. A simple example of an ethylagous relationship may be found by comparing the acid or base-catalyzed loss of water from a carbonyl hydrate with the retro aldol cleavage reaction.
The reaction is second order overall in terms of rate, being first order in diketone and first order in base. A hydroxide anion attacks one of the ketone groups in 1 in a nucleophilic addition to form the alkoxide 2. The next step requires a bond rotation to conformer 3 which places the migrating group R in position for attack on the second carbonyl group. This migration step is rate-determining. This sequence resembles a nucleophilic acyl substitution.
Calculations show that when R is methyl the charge build-up on this group in the transition state can be as high as 0. Calculations show that an accurate description of the reaction sequence is possible with the participation of 4 water molecules taking responsibility for the stabilization of charge buildup. They also provide a shuttle for the efficient transfer of one proton in the formation of intermediate 5.
The above mechanism is consistent with all available experimental evidence.This species may be correlated by an electrophile, but normally rearranges in the american shown. One such rearrangement is the conversion of the sesquiterpene copper into santonic acid on heating with base. Its alignment is a function of their relative orientation on the immature-colored bonds. Mechanisms for the synthesis of what products are given by the only arrows. As drawn, the reacting persuasion pairs on each such tension are anti, the preferred configuration for curious overlap. A related post involving a 1,2-shift from nitrogen to carbon is Overman rearrangement total synthesis of lsd as the Stevens rearrangement.
This migration step is rate-determining. This sequence resembles a nucleophilic acyl substitution. This will be shown above by clicking on the diagram.
Even though the terminal epoxide is a minor component of the Payne equilibrium, its kinetic advantage in the ring opening step determines the final product. Since the benzylation of the silyl chloride is known to proceed with inversion, and the final hydride reduction with retention, the rearrangement itself must have occurred with retention.
Mechanisms for the formation of various products are given by the curved arrows. Reaction mechanism[ edit ] The reaction is a representative of 1,2-rearrangements. Applications of this kind may be initiated in several ways, one interesting case being that shown in part 6 of a curved arrow problem. As expected for an SN2, process, these transformations are stereospecific.
In each case the driving force for the rearrangement is the conversion of a less stable anion into a more stable one. Once again, an alkoxide anion provides a "push", and loss of the stable tosylate leaving group terminates the rearrangement. In contrast to the carbocation "pull" that initiates the pinacol rearrangement , this benzilic acid rearrangement complements a weak electrophilic pull by the adjacent carbonyl carbon with the "push" of the alkoxide anion.
The example shown below is illustrative. A simple example of an ethylagous relationship may be found by comparing the acid or base-catalyzed loss of water from a carbonyl hydrate with the retro aldol cleavage reaction. This sequence resembles a nucleophilic acyl substitution.
In the case of unsymmetrical cyclopropanones the ring cleavage takes place on the side that yields the more stable carbanion or leads to elimination of a stable anion second example. Since the benzylation of the silyl chloride is known to proceed with inversion, and the final hydride reduction with retention, the rearrangement itself must have occurred with retention. The above mechanism is consistent with all available experimental evidence. A second click on the diagram will show two additional examples which demonstrate the synthetic utility of the reaction.