Ketones ring contraction

Unsaturated ketones, ring-contracted ketones, and bicyclic ketones resulting from transannular insertion are the main products isolated in the oxidation of cycloalkynes.738 Product distribution was interpreted in terms of an oxirene-a-ketocarbene equilibrium. 

The Favorskii rearrangement results from the action of base on an a-halo ketone. When applied to cyclic ketones, ring contraction results, as shown in the classic case of cyclohexanone formulated below. 

With cyclic ketones ring contraction usually occurs to give the corresponding... 

In the case of cyclic a-halo ketones, ring contraction occurs. A similar reaction occurs on )0-halo ketones via the elimination of a hydrogen halide to cyclobutanone followed by the scission of cyclobutanone, known as the homo-Favorskii rearrangement.This reaction has been proved to be a useful tool for synthesizing the highly strained esters. 

An oxidative rearrangement may take place when alkenes and ketones are treated with some oxidants, such as thallium(III)" and hypervalent iodine(III). When applied to cyclic alkenes and ketones, ring contraction may be observed, as discussed in the following paragraphs for selected examples mainly regarding the total synthesis of biologically active compounds. 

Oxidative rearrangement takes place in the oxidation of the 1-vinyl-l-cyclo-butanol 31, yielding the cyclopentenone derivative 32[84], Ring contraction to cyclopropyl methyl ketone (34) is observed by the oxidation of 1-methylcyclo-butene (33)[85], and ring expansion to cyclopentanone takes place by the reaction of the methylenecyclobutane 35. [86,87]... 

Schmidt reaction of ketones, 7, 530 from thienylnitrenes, 4, 820 tautomers, 7, 492 thermal reactions, 7, 503 transition metal complexes reactivity, 7, 28 tungsten complexes, 7, 523 UV spectra, 7, 501 X-ray analysis, 7, 494 1 H-Azepines conformation, 7, 492 cycloaddition reactions, 7, 520, 522 dimerization, 7, 508 H NMR, 7, 495 isomerization, 7, 519 metal complexes, 7, 512 photoaddition reactions with oxygen, 7, 523 protonation, 7, 509 ring contractions, 7, 506 sigmatropic rearrangements, 7, 506 stability, 7, 492 N-substituted mass spectra, 7, 501 rearrangements, 7, 504 synthesis, 7, 536-537... 

The procedure described is essentially that of Shioiri and Yamada. Diphenyl phosphorazidate is a useful and versatile reagent in organic synthesis. It has been used for racemlzatlon-free peptide syntheses, thiol ester synthesis, a modified Curtius reaction, an esterification of a-substituted carboxylic acld, formation of diketoplperazines, alkyl azide synthesis, phosphorylation of alcohols and amines,and polymerization of amino acids and peptides. - Furthermore, diphenyl phosphorazidate acts as a nitrene source and as a 1,3-dipole.An example in the ring contraction of cyclic ketones to form cycloalkanecarboxylic acids is presented in the next procedure, this volume. 

The present preparation illustrates a general and convenient irethod for ring contraction of cyclic ketones. The first step is the usual procedure for the preparation of enamines. The second step involves 1,3-dipolar cycloaddition of diphenyl phosphorazidate to an enamine followed by ring contraction with evolution of nitrogen. Ethyl acetate and tetrahydrofuran can be used as a solvent in place of toluene. Pyrrolidine enamines from various cyclic ketones smoothly undergo the reaction under similar reaction conditions. Diphenyl (cycloalkyl-1-pyrrolidinylmethylene)phosphoramidates with 5,6,7, and 15 members in the ring have been prepared in yields of 68-76%. 

This group has also developed two ring-contraction systems of potential use in crown synthesis. In the first of these, extrusion of a phenylphosphine oxide unit results from treatment with alkoxide ion. In the second, similar conditions initiated decarbonyla-tion of a bis-pyridyl ketone Despite the apparent potential of these methods for crown synthesis, direct formation of crowns by processes which involve them do not appear to have enjoyed great success thus far. 

Analogous ring contractions carried out with enamines of 5j5-3-ketones... 

The reaction of cyanogen azide with enamines of cyclic ketones to yield a cyanoamidine with one less member in the carbocyclic ring represents a potentially valuable method of ring contraction under mild conditions (199a). The reaction probably proceeds first by 1,3 cycloaddition of the azide to the enamine followed by rearrangement and elimination of a molecule of nitrogen. 

The application of this addition to aminomethylene ketones provides a convenient synthesis of monoamides of pimelic acid (508). It should be noted that the corresponding oxidation of hydroxy methylene cyclohexanone leads to ring contraction and formation of cyclopentanoic acid. 

Dimethylfuran, in a sensitized reaction, gave 1,3-dimethylcyclopropene (the main product), isoprene, cis- and rran.s-l,3-pentadiene, 2-pentyne, and 1-methylcyclopropenyl methyl ketone (Scheme 7) (70JPC574) the ring contraction showed a high selectivity. 

With cyclic a-halo ketones, e.g. 2-chloro cyclohexanone 6, the Favorskii rearrangement leads to a ring contraction by one carbon atom. This type of reaction has for example found application as a key step in the synthesis of cubane by Eaton and Cole for the construction of the cubic carbon skeleton ... 

The rearrangement with ring contraction probably is the most important synthetic application of the Favorskii reaction it is for example used in the synthesis of steroids. Yields can vary from good to moderate. As solvents diethyl ether or alcohols are often used. With acyclic a-halo ketones bearing voluminous substituents in a -position, yields can be low a tcrt-butyl substituent will prevent the rearrangement. 

The photolytic cleavage of cyclic ketones 14 leads to formation of a diradical species, that can undergo analogously the various reactions outlined above. The decarbonylation followed by intramolecular recombination yields a ring-contracted cycloalkane 15 ... 

With cyclic a-diazo ketones, e.g. a-diazo cyclohexanone 9, the rearrangement results in a ring contraction by one carbon " ... 

The Fuvorskii reaction involves treatment of an a-bromo ketone with base to yield a ring-contracted product, for example, reaction of 2-bromocyclo-hexanone with aqueous NaOH yields cyclopentanecarboxylic acid. Propose a mechanism. 

Dialkyl-5//-dibenz[/>,/]azepines 6 on oxidation with 3-chloroperoxybenzoic acid undergo ring contraction to 9,10-dihydroacridinc-9-carbaldehydes 7.223 In contrast, 5,10,11-trialkyl derivatives 8 yield mixtures of the acridinyl ketones 9 and 10,11-epoxides 10. 

Though the reaction is not general, certain cyclic ketones can be photolyzed to give ring-contracted products.In the example above, the cyclobutanone (55) was photolyzed to give (56), where BZ is benzoyl. This reaction was used to synthesize tetra-r rf-butyltetrahedrane (57). 

Ring contraction of cyclic diazo ketones (Wolff)... 

By analogy with die acid-induced ring contraction of cycloheptatrienyl ketones 233, high-yield rearrangement to 2-tetralones is possible 233 >. As Scheme 32 shows, substituents on the aromatic nucleus determine the regioselectivity of cyclopropa-... 

Ring contractions of pyran derivatives are occasionally valuable. The contraction of 3-halo-2-pyrones to 2-furoic acids under the influence of alkali has been studied and the conditions defined.58112113 The method is adaptable to the preparation of 3-furoic acid via furan-2,4-dicarboxylic acid58 and of 3,4,5-triphenylfuran-2-carboxylic acid.113 Another ring contraction involving halides is the conversion of 4-chloromethylpyrylium salts into furylmethyl ketones as indicated in Scheme 21.114 Pyridine oxides may be transformed with unexpected ease into furans through treatment with a thiol (Scheme 22).115... 

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