Ring contraction carboxylic acids, cyclic

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. 

A third possibility arises when R and R are directly linked such that (9) is a cyclic a-diazo ketone. Rearrangement to (14) therefore represents a ring contraction, and trapping by RXH affords the ring-contracted carboxylic acid derivative (15). This area is covered in Section 3.9.3.2. 

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. 

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.

Fig. 11.27. Ring contraction via Wolff rearrangement. The 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

Favorskii rearrangement of cyclic 2-bromoketones leads to ring contraction and this has become one of the most fruitful uses of the rearrangement in synthesis. Bromination of cyclohexanone is a simple reaction (Chapter 21) and treatment with methoxide gives the methyl ester of cyclopentane carboxylic acid in good yield. 

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. 

Wolff rearrangement in organic synthesis are the homologation of carboxylic acids (Arndt-Eistert reaction), the one-carbon ring contraction of cyclic a-diazoketones, and, more generally, the in situ production of ketenes and a-oxo-ketenes as reactive intermediates under additive-free and coproduct-free conditions (except for the inert N2 gas). 

When a-haloketones are treated with a nucleophilic base in protic or ethereal solvents, a transformation known as the Favorskii rearrangement occurs to yield carboxylic acid derivatives. Depending on the identity of the incorporated base the final product will be a carboxylic acid, ester, or amide. Cyclic a-haloketones undergo a ring contraction during the course of the rearrangement. 

In 1894, Alexie Favorskii published an early account of the rearrangement of simple acyclic a-halo ketones. This was followed in subsequent years with additional reports/ In 1914, he published the cyclic version featuring the ring contraction of 2-chlorocyclohexanone. This modification makes this transformation a reliable way to sjmthesize 1-substituted cycloalkane carboxylic acid derivatives. Later in the century, the rearrangement found application in the modification of steroids. Only in the last half of the 20 century has a clearer picture of the mechanism appeared. ... 

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). 

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