8 Rearrangements of Carbanions and Free Radicals.

Name: 8 Rearrangements of Carbanions and Free Radicals.
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Description: 8 Rearrangements of Carbanions and Free Radicals.

8 Rearrangements of Carbanions and Free Radicals

Carbanion Rearrangements
Sigmatropic Shifts in Hydrocarbon Anions Rearrangements of carbanions are far less common than that of carbocations. 1,2-Shifts of alkyl groups or hydrogen atoms in alkali or alkali earth derivatives of hydrocarbon do not occur. (2) Suprafacial [1,4] migration in allylic carbanions does not seem to occur. (3) Several examples of [1,6] hydrogen migrations in pentadienyl anions showed intramolecular processes instead of intermolecular processes, in which hydrogen shifts occur readily at temperature as low as 35 oC. (4) Thermal rearrangements of pentadienyl anions proceed by antarafacial paths.

Sigmatropic Shifts in Hydrocarbon Anions

Sigmatropic Shifts in Hydrocarbon Anions Rearrangements of carbanions are far less common than that of carbocations. (5) [1,8] Alkyl group migration occurs in the rearrangement of carbanion 3, although the possibility of a two-step elimination-addition mechanism has not been eliminated.

Sigmatropic Shifts in Hydrocarbon Anions Rearrangements of carbanions are far less common than that of carbocations. (6) Migration of allylic group in carbanions proceed by allowed [2,3] shifts

Sigmatropic Shifts in Hydrocarbon Anions However, as the reaction temperature are raised, increasing amount of 1,2-migration products are formed by free-radical dissociation-recombination mechanisms.

Addition-Elimination Mechanisms Migrations of vinyl groups In contrast to alkyl groups, vinyl groups and aromatic rings do undergo 1,2-migration in carbanions. C1 and C2 of 3-butenyl (homoallylic) Grignard reagents slowly interchange positions via initial addition of the “carbanionoid” carbon to the double bond. This rearrangement are slow at room temperature.

Addition-Elimination Mechanisms Migrations of vinyl groups Similar rearrangements of lithium reagents can be quite rapid.

Addition-Elimination Mechanisms Aryl group migrations Phenyl groups do undergo slow 1,2-migrations in lithium reagents, and rapid 1,2-migrations in organosodium, organo potassium, or organocesium reagents provided that at least one aryl group remains at the migration origin to stabilize the resulting anoin.

Addition-Elimination Mechanisms Aryl group migrations Rearrangements proceed by addition-elimination mechanism involving three-membered ring intermediates rather than by [1,2] sigmatropic shifts.

Addition-Elimination Mechanisms Aryl group migrations The cesium reagent 4 reacts with carbon dioxide to yield a cyclopropyl derivative as the principal product.

Addition-Elimination Mechanisms Aryl group migrations The relative migratory aptitudes of different aromatic rings are consistent with migrations in carbanions rather than in free radicals. Phenyl group migrate more rapidly than para-methylphenyl groups

Addition-Elimination Mechanisms Rearrangements via homoenolate anions Similar reactions which the carbanionic sites could add to the carbonyl groups to form cyclopropoxide anions occur much more rapidly in homoenolate anoins.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements 1,2-Shifts of alkyl groups are common when the negatively charged carbons are substituted with oxygen, nitrogen, or sulfur atoms. 1942, Georg Wittig

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements 1,2-Shifts of alkyl groups are common when the negatively charged carbons are substituted with oxygen, nitrogen, or sulfur atoms. Yields of rearrangement products are often low if the ethers can undergo elimination reactions.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements Wiitig first suggested that the rearrangements proceed by elimination-addition mechanism via observation of racemization of chiral migrating groups. And also alkyllithium can be incorporated into the rearrangement products.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements Evidence for the proposed mechanism Alkyl groups from the alkyllithium reagents can be incorporated into the rearrangement products, if excess amounts of alkyllithium reagents are employed.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements Rearrangements proceed by homolytic dissociation of the carbon oxygen bonds, followed by recombination of the resulting alkyl radicals and ketyl radical anions. Evidences the yields of Wittig rearrangement products increase as the migrating groups change from primary to tertiary alkyl group. (2) Migration of a 5-hexenyl group yields the cyclopentylmethyl derivatives. 5-Hexenyl radicals are known to cyclize rapidly cyclopentylmethyl radicals.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements Evidence 2 for the proposed mechanism

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements Rearrangements proceed by homolytic dissociation of the carbon oxygen bonds, followed by recombination of the resulting alkyl radicals and ketyl radical anions. The incorporation of alkyl groups from alkyllithium reagents can be explained by electron exchange reactions of the lithium reagents with alkyl radicals.

Rearrangements of a-Hetero Carbanions 1,2- and 1,4-Shifts in Wittig rearrangements In Wittig rearrangements of allylic carbanions, 1,4-shifts can accompany 1,2-migrations 1,4-Wittig migrations proceed by free-radical dissociation-recombination mechanisms

Rearrangements of a-Hetero Carbanions [2,3] Wittig rearrangements Migration of allylic groups in Wittig rearrangements proceed via [2,3] paths and result in inversion of the allylic structures. 1,2-Migrations may also occur at relatively high temperature which would favor homolytic dissociation steps.

Rearrangements of a-Hetero Carbanions [2,3] Wittig rearrangements Since it is often difficult to form the precursors for [2,3] Wittig rearrangements by abstraction of protons from allyl alkyl ethers, some other methods can be used. Electron-transfer mechanism

Rearrangements of a-Hetero Carbanions [2,3] Wittig rearrangements Since it is often difficult to form the precursors for [2,3] Wittig rearrangements by abstraction of protons from allyl alkyl ethers, some other methods can be used.

Rearrangements of a-Hetero Carbanions Use in synthesis If a carbon-oxygen bond to a chiral center is broken in a [2,3] Wittig rearrangement, the new carbon-carbon bond will be formed with nearly complete transfer of chirality.

Rearrangements of a-Hetero Carbanions Use in synthesis The rearrangement proceeds with complete inversion at the anionic carbon. Therefore, [2,3] Wittig rearrangement proceeds by concerted and cyclic mechanism instead of free-radical one.

Rearrangements of Yields Stevens rearrangements Generation of ylides (common)

Rearrangements of Yields Stevens rearrangements Generation of ylides (less common)

Rearrangements of Yields Stevens rearrangements alkyl and benzyl groups in ammonium and sulfonium ylides can migrate from the positively charged nitrogen or sulfur atoms to the adjacent negatively charged carbon atoms. These reactions are often so rapid that the ylides cannot even be detected before they rearrange. Stabilized ylides by carbonyl groups have longer lifetimes and may be isolated as crystalline salts.

Rearrangements of Yields Stevens rearrangements These rearrangements have proven to be very useful methods for the formation of new carbon-carbon bonds.

Rearrangements of Yields Stevens rearrangements Ylides containing allylic anions can undergo 1,4- as well as 1,2-Stevens rearrangements. 1,2- rearrangements often proceed with nearly complete retention of the configurations of chiral migrating groups. However, it was later shown that rearrangements proceed by dissociation-recombination mechanism.

Rearrangements of Yields Stevens rearrangements Rearrangements of sulfonium ylides appear to proceed by free-radical dissociation-recombination processes. They result in significant racemization of chiral migrating groups. Intermolecular cross-products from rearrangements of mixtures of ylides and recombination product of free radicals

Rearrangements of Yields Sommelet-Hauser rearrangements [2,3] Migrations of allylic groups in ylides in preference to Stevens rearrangements +

Rearrangements of Yields Sommelet-Hauser rearrangements These rearrangements take precedence over Stevens rearrangements even when the double bond participating in the reaction is part of an aromatic ring. Proceed by a [2,3] migration +

Rearrangements of Yields Sommelet-Hauser rearrangements In some instances, Stevens rearrangements accompany Sommelet-Hauser rearrangements, but the products from Sommelet-Hauser rearrangements usually predominate. The final tautomerism cannot take place

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements The reactions of a-haloketones or a,b-epoxyketones with hydroxide, alkoxide, or amide anions yield carboxylic acid derivatives resulting from the migration of an alkyl group from the carbonyl group to the a-carbon.

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements Proposed mechanism

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements Bulky substituent Less bulky substituent

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements The reactions of a,a’-dibromoketones with triethylamine yield stable cyclopropenone derivatives.

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements Internal SN2 displacements of halide ions result in inversions of configurations of the halogenated carbons.

Rearrangements Resulting from Intramolecular Substitution Reactions Favorskii rearrangements In the absence of resonance stabilization of one of the two possible anions, the less-substituted alkyl anion is formed.

Rearrangements Resulting from Intramolecular Substitution Reactions Quasi-Favorskii rearrangements Many ketones lacking hydrogens on their unhalogenated a-carbon undergo reactions that yield products of Favorskii rearrangements.

Rearrangements Resulting from Intramolecular Substitution Reactions Quasi-Favorskii rearrangements

Rearrangements Resulting from Intramolecular Substitution Reactions The Ramburg-Backlund reaction An a-halosulfone reacts with base to yield an alkene formed by joining the two alkyl groups of sulfone by a double bond.

Rearrangements Resulting from Intramolecular Substitution Reactions The Ramburg-Backlund reaction Proposed mechanism After the initial formation of a-sulfonyl carbanions, internal nucleophilic displacements of halide anions result in the formation of three-membered sulfone rings and then remove the SO2 to give cycloalkene.

Rearrangements Resulting from Intramolecular Substitution Reactions The Ramburg-Backlund reaction Dihalosulfones can result in the formation of alkynes, vinyl halides, and salts of sulfonic acids.

Rearrangements Resulting from Intramolecular Substitution Reactions The Ramburg-Backlund reaction If tertiary amines are employed as the bases, however, unsaturated cyclic sulfones can be isolated.

Rearrangements Resulting from Intramolecular Substitution Reactions The Neber reaction The reactions of oxime tosylates or of N-chloroimines with strong bases result in migrations of nitrogen atoms to form a-amino ketones.

Rearrangements Resulting from Intramolecular Substitution Reactions The Neber reaction When these reactions are carried out at low temperatures or in the absence of hydroxylic solvents, it is possible to isolate azirines.

Rearrangements of Free Radicals
The formation of Free Radicals Decarbonylation of aldehydes Hydrogen abstraction processes are not useful for forming free radicals with specific structures Disadvantage is that there are several different Position from which hydrogens can be removed.

The formation of Free Radicals Decarbonylation of aldehydes The free radical reactions with aldehydes usually result in selective attack at the hydrogens bonded to the carbonyl groups to give acyl radicals which lose CO to form alkyl or aryl radicals.

The formation of Free Radicals Reduction by tin hydrides Reaction of organic halides with trialkyltin hydrides reduce carbon-halogen bonds to carbon-hydrogen bonds.

The formation of Free Radicals Decomposition of peroxides Thermal cleavage of the oxygen-oxygen bonds in diacyl peroxides results in the formation of carbalkoxy radicals which lose CO2 to form hydrocarbon radicals.

The formation of Free Radicals Decomposition of peroxides The alkyl radicals may abstract hydrogen or halogen atoms from solvent or other molecules in solution, or may add to double bonds, or may undergo dimerization or dispropotion- ation.

Sigmatropic Shifts [1,n] Rearrangements Suprafacial [1,2] shifts in free redicals are forbidden. However, [1,3] ans [1,4] shifts of hydrogen atoms do appear to take place if the rearrangement steps are highly exothermic. Traces of benzyl chloride from 1,3-hydrogen migrations in 2-methylphenyl radicals are obtained from the 2-methylbenzoyl peroxide in CCl4.

Sigmatropic Shifts [1,n] Rearrangements Phenoxy radicals are similarly obtained from reactions that should from 2-hydroxyphenyl radicals. Less exothermic than previous reaction

Sigmatropic Shifts [1,n] Rearrangements 1,4-Hydrogen migrations in free radicals.

Sigmatropic Shifts [1,n] Rearrangements 1,5-Hydrogen migrations in free radicals are common reactions

Sigmatropic Shifts [1,n] Rearrangements

Sigmatropic Shifts [1,n] Rearrangements 1,5-Migrations of hydrogen atoms in alkoxy radicals have been utilized to selectively introduce oxygen and nitrogen atoms onto unactivated positions of steroid molecules.

Sigmatropic Shifts [2,3] Rearrangements Acyloxy groups rapidly migrate to adjacent radical centers, in which these rearrangements proceed by concerted [2,3] shifts. Dioxanyl radicals 14 do not open to acyloxy groups at the temperatures at which the migrations of acyloxy groups take place.

Sigmatropic Shifts Migrations of peroxy groups Allyperoxy radicals undergo allylic shifts of the dioxygen units. The peroxy function initially remained on the same face of the ring system in the product as in the starting material. Rearrangement can Not proceed via an intermediate carbon-cantered radical such as 16.

Sigmatropic Shifts Migrations of peroxy groups Proposed mechanism involved a dissociation of allylperoxy radical to give oxygen and allylic radical, and then recombination of two fragments to form the rearranged allylperoxy radical.

Sigmatropic Shifts Rearrangements by addition-elimination mechanisms Vinyl groups undergo rapid 1,2-migrations in free radicals in which the rearrangements proceed by cyclization of the original homoallylic radicals to form cyclopropylmethyl radicals, which may then reopen to form rearranged radicals

Sigmatropic Shifts Rearrangements by addition-elimination mechanisms 1,2-Migration of aromatic rings occur readily in neophyl radicals and other radicals with aromatic rings on carbon atoms joined to radical centers. The rearrangements are favored by the presence of radical stabilizing groups at the migration origins.

Sigmatropic Shifts Rearrangements by addition-elimination mechanisms 1,4-Migrations of aromatic rings in free radicals are also well known.

Sigmatropic Shifts Rearrangements by addition-elimination mechanisms

Sigmatropic Shifts Rearrangements by addition-elimination mechanisms A transannular 1,5-migration of a phenyl group has also been reported. 1,4-migration of an acetyl group

The Bergman and Myers-Saito Reactions
The Bergman Reaction When the compound 17 was heated at 200 oC, deuterium atoms shifted from the terminal acetylene positions to vinyl positions at the interior of the chain. When the reaction was carried out in the presence of 1,4-dihydrobenzene the starting materials was converted to benzene, while in CCl4 solution p-dichlorobenzene was formed.

The Bergman Reaction Bergman reactions could proceed at much lower temperature if the enediyne system was contained in a relatively small ring. Bergman reactions are also possible if the double bonds of the enediynes comprise parts of aromatic rings.

Biological Examples A series of powerful antibiotics and anticancer agents owe their biological powers to the formation of diradicals via Bergman reactions.

Biological Examples (1) In biological systems, nucleophiles attack the trisulfide moieties of the calchicheamins, releasing mercaptide anions which then add to b carbons of the conjugated carbonyl systems. (2) Conversion of a vinyl b carbon ro an sp3 hybridized form reduces the distance between positions 1 and 6 of the enediyne moiety, thus facilitating bond formation between the two acetylenic groups to form aromatic diradicals (3) The diradicals can then abstract hydrogens from the deoxyribose rings of DNA, thus destroying the DNA.

Biological Examples Myers and Saito reported that allenylalkynes such as 18 are converted to diradicals at temperatures barely above those in mammalian bodies.

Biological Examples Myers and Saito reported that reaction of 18 in methanol yields benzyl methyl ether. This suggests that intermediate “diradical” has dipolar properties.

8 Rearrangements of Carbanions and Free Radicals.

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