Ring contraction ketones, cyclic

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%. 

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

Figure 3.60 Ring contraction of cyclic ketones with selenium dioxide in the presence of hydrogen peroxide.

Three highly useful synthetic transformations are presented in this section the synthesis of isoflavones from chalcones, the synthesis of a-arylalkanones fmm arylalkenes, and the synthesis of a-arylalkanoic acids from aryl ketones. Two others are potentially useful methods, but are not as yet widely used the preparation of a-branched carboxylic acids from a ynes, and the ring expansion and ring contraction of cyclic alkenes and ketones. 

Carvone-derived 2,3-epoxy alcohol derivatives (317) have been found to rearrange with stereoselective formation of ring-contracted ketones (318) in a process where the stereochemical result seems to be independent of epoxide configuration. On the basis of this study, the authors concluded that the rearrangement of tetrasubstituted cyclic epoxy alcohol derivatives remains a transformation for which both regiose-lectivity and stereochemical outcome are difficult to predict. New solid acid catalysts based on silica-supported zinc triflate have been prepared for use in the rearrangement of a-pinene oxide to campholenic aldehyde. ... 

SOCI2 added during 5 min. to a suspension of 2-hydroxyadamantane-2-carboxylic acid-2-r- C in benzene, stirred and refluxed 3 hrs. 2-adamantanone-2- C. Y 92%. - This is one step of a 3-step ring contraction of cyclic ketones. S. H. Liggero et al., J. Labelled Compds. 7, 3 (1971). 

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. 

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 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 " ... 

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). 

The photolysis of cyclic diazo ketones in hydroxylic solvents leads to ring contracted carboxylic acid derivatives via this ketocarbene -> ketene rearrangement. Examples of such reactions are given in (2.24)239) and (2.25) 240). In this last example a photoequilibrium between the diazo ketone and its valence isomer, a diazirine, has been observed, both products then eliminating nitrogen to afford the cyclobutane carboxylic acid. 

This reaction is known as the Favorskii rearrangement,37 If the ketone is cyclic, a ring contraction occurs. 

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. 

Fig. 14.29. Preparation of an a-diazoketone (compound E) from a ketone (A) and subsequent Wolff rearrangement of the a-diazoketone. Initially, A is transformed to give the enolate B of its a-formyl derivative. In a Regitz diazo group transfer reaction, this will then be converted into the a-diazoketone E. Ring contraction via Wolff rearrangement occurs and the 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

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