6.5 [3,3]Sigmatropic Rearrangements

The principles of orbial symmetry established that concerted [3,3] sigmatropic rearrangements are allowed processes.

Stereochemical predictions and analyses are based on the cyclic transitionstate implied by a concerted reaction mechanism.

6.5.1. Cope Rearrangements

The cope rearrangement is the conversion of a 1,5-hexadiene derivatives to an isomeric 1,5-hexadiene by the [3,3] sigmatropic mechanism.

When a chair transition state is favored, the E,E- and Z,Z-dienes lead toanti-3,4-diastereomers whereas the E,Z and Z.E-isomers give the 3,4-synproduct.

Transition state B is less favorable than A because of the axial placementof the larger phenyl substituent.

favorable

The products corresponding to boatlike transition states are usually not observedfor acyclic dienes. However, the boatlike transition state is allowed, and if stericfactors make a boat transition state preferable to a chair, reaction will proceed through a boat.

The position of the final equilibrium is governed by the relative stability of the starting material and the product.

The equilibrium is favorable for product formation because the product isstabilized by conjugation of the alkene with the phenyl ring or the doublebonds in the product are more highly substituted, and therefore more stable. (Scheme 6.11, entries 1 & 2)

In the ring strained molecules, the Cope rearrangements can occur at much lower temperatures and with complete conversion to ring-openedproducts.

-40oC

With transition metal catalysts, such as PdCl2(CH3CN)2

The rearrangements occurs at r.t., as contrasted to 240oC in its absence.

The electrophilic character of Pd(II) facilitates the reaction.

Oxy-Cope rearrangement: The formation of the carbonyl compoundprovides a net driving force for the reaction. The reaction is catalyzed bybase. When the C-3 hydroxyl group is converted to its alkoxide the reaction is accelerated by factors of 1010-1017, which is called anionOxy-Cope rearrangements. The reactivity trend is K+>Na+>Li+.

Catalysis of Claisen rearrangements has been achieved using highly hinderedbis(phenoxy)methylaluminum as a Lewis acid for E/Z control of the products.

Very bulky catalysts tend to favor the Z-isomer by forcing the -substituent ofthe allyl group into an axial conformation.

Several variation of the Claisen rearrangement .

Scheme 6.12. Claisen Rearrangments

The configuration of the new chiral center is that predicted by a chairliketransition state with the methyl group occupying a pseudoequatorial position.

The stereochemistry of the silyl enol ether Claisen rearrangement is controlled not only by the stereochemistry of the double bond in the allyl alcohol but alsoby the stereochemistry of the silyl enol ether.

If the enolate is prepared in pure THF, the E-enolate is generated. But ifHMPA is included in the solvent, the Z-enolate predominates due to acyclictransition state.

E-silyl enol ethers rearrange somewhat more slowly than the corresponding Z-isomers, This is interpreted as resulting from the pseudoaxial placement of the methyl group in the E-transition state.

The larger R accelerates the reaction rate, because the steric interaction withR are relieved as the C-O bond stretches. The rate acceleration would reflectthe higher ground state energy resulting from these interactions.

The enolates of -alkoxy esters give the Z-silyl derivatives because ofchelation by the alkoxy substituent.

The E-isomer gives a syn orientation whereas the Z-isomer gives rise toanti -stereochemistry.

O-Allyl imidate esters undergo [3,3] sigmatropic rearrangements to N-allyl amides.

Yields in the reaction are sometimes improved by inclusion of K2CO3 in thereaction mixture.

Imidates rearrangements are catalyzed by palladium salts.

Aryl allyl ethers can undergo [3,3] sigmatropic rearrangement.

If both ortho-positions are substituted, the allyl group undergoes a secondsigmatropic migration, giving the para-substituted phenol.

6.6. [2,3] Sigmatropic Rearrangements

The rearrangements of allylic sulfoxide, selenoxide, and nitrones are the mostuseful examples of the first type whereas rearrangements of carbanions of aallyl ethers are the major examples of the anionic type.

Phenyl thiolate to cleaveS-O bond

Allylic sulfonium ylides readily undergo [2,3] sigmatropic rearrangement.

Ring expansion sequence for generation of Medium-sized rings.

X = N and Y = O-

Anilinosulfonium ylides

The Wittig rearrangement in which a strong base converts allylic ethers to-allyl alkoxides. Because the deprotonation at the ’carbon must cmparewith deprotonation of the carbon in the allyl group.

Cyclic 5-membered ring transition state in which the substituent prefersan equatorial orientation.

6.7 Ene Reaction

Certain electrophilic carbon-carbon and carbon-oxygen bonds can undergoan addition reaction with alkenes in which an allylic hydrogen is transferredto the electrophile.

Ene reaction have relatively high activation energies and intermolecularreaction is observed only for strongly electrophilic enophiles.

The thermal ene reaction of carbonyl compounds generally requires electron-attracting substituents. The reaction shows a primary kinetic isotopic effectindicative of C-H bond breaking in the rate determining step. The observations are consistent with a concerted process.

The ene reaction is strongly catalyzed by Lewis acids such as aluminum chlorideand diethylaluminum chloride. Coordination by the aluminum at the carbonylgroup increases the electrophilicity of the conjugated system and allowsreaction to occur below room temperature, as illustrated in entry 6.

6.8 Unimolecular Thermal Elimination Reactions

6.8.1. Cheletropic Elimination

The atom X is normally bound to other atoms in such a way that eliminationwill give rise to a stable molecule.

The stereochemistry is consistent with conservation of orbital symmetry.

-

6.8.2 Decomposition of Cyclic Azo Compounds

X-Y = -N=N-

16 decomposes to norbornene and nitrogen only above 100oC. But 17eliminates nitrogen immediately on preparation, even at -78oC. Becausea C-N bond must be broken without concomitant compensation by carbon-carbon bond formation, the activation energy is much higher than for aconcerted process.

[2 + 2] forbidden (high energy)

[2 + 4] allowed (low energy)

photochemically

Nonconcerted diradical mechanism

The stereochemistry varies from case to case.

Pyridazine-3,6-dicarboxylate ester react with electron-rich alkenes

1,2,4-triazine and 1,2,4,5-tetrazines

Heteroaromatic ring

6.8.3. -elimination involving cyclic transition state

Thermal syn elimination

Amine oxide pyrolysis occurs at temperatures of 100-150oC. The reactioncan proceed at room temperature in DMSO.

These reaction is thermally activated unimolecular reactions that normally donot involve acidic or basic catalysts.