Ring contraction reactions Wolff rearrangement

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.

Other than Arndt-Eistert reactions and related transformations, applications of the Wolff rearrangement of a-diazocarbonyl conpounds principally concern ring contraction reactions. The method is particularly valuable for the preparation of strained ring systems such as cyclobutane derivatives. For exanple, the photochemical Wolff rearrangement of 2-diazo-3-... 

Scheme 10.14 gives some other examples of Wolff rearrangement reactions. Entries 1 and 2 are reactions carried out under the classical silver ion catalysis conditions. Entry 3 is an example of a thermolysis. Entries 4 to 7 are ring contractions done under photolytic conditions. Entry 8, done using a silver catalyst, was a step in the synthesis of macbecin, an antitumor antibiotic. Entry 9, a step in the synthesis of a drug candidate, illustrates direct formation of an amide by trapping the ketene intermediate with an amine. 

In the first step of the reaction sequence a methyl ester is formed via a Wolff rearrangement. The Wolff rearrangem ent provides acids, esters or amides from a-diazo ketones and is often used in a ring contractive way to form strained ring systems, which are not accessible by other sequences.It also occurs as the key step in the Arndt-Eistert homologation of carboxylic acids. ... 

In the laboratory of K. Fukumoto, the stereoselective total synthesis of (+)-A -capnellene was carried out using an intramolecular Diels-Alder reaction to obtain a tricyclic 5-5-6 system. Since the target molecule was a triquinane, the six-membered ring had to be converted to a five-membered one, a transformation achieved by a Wolff rearrangement. The required a-diazo ketone was prepared via a deformylative diazo transfer reaction and was photolyzed in methanol. The ring-contracted methyl ester was isolated as a 3 1 mixture of separable isomers favoring the a-isomer. 

Sus and his co-workers179 have applied the Wolff-Schroter rearrangement to 0-quinone diazides, which are accessible by diazotization of o-aminophenols and subsequent treatment with alkali. When irradiated, the quinone diazides lose nitrogen and pass into ketenes by ring contraction the ketenes are isolated as acids since the reaction is always effected in water. 

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). 

The 3-diazoniumtetrafluoroborates 64 were obtained in good yields via nitrosation of 3-aminoquinolizines 63. Treatment of 64 with anhydrous alcohol afforded a mixture of alkyl indolizine-3-carboxylates 67 and the 3-unsubstituted 4/f-quinolizin-4-ones 68. The product selectivity of this reaction depends upon the alcohol. The formation of indolizine 67 has been regarded as an aza Wolff rearrangement through ring contraction via 65 and... 

The first total synthesis of the antibiotic acanthodoral (1) 118 has been achieved from 3-methyl-2-cyclohexen-l-one in 19 steps in 2.1% overall yield. This synthesis involves the use of a Pd-ene reaction in the presence of CO to form the endocyclic alkene 116, a nonreductive acyl radical cyclization and ring contraction by the Wolff rearrangement of ll ." ... 

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