Diazo-ketones, rearrangement

The suitably protected amino acid is activated as the mixed anhydride and treated with diazomethane to produce the corresponding diazo ketone. Rearrangement in the presence of water furnishes the p-amino acid. Diazomethane contains varying amounts of water, which is able to hydrolyze the activated amino acid. This leads to subsequent methylation by diazomethane to form the methyl ester as a side product. This cannot easily be removed from the diazo ketone, but can be separated during work-up of the homologated amino acids. 

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. 

Rearrangement of the diazo ketone, with loss of nitrogen, in the presence of suitable reagents and a catalyst (colloidal silver, silver oxide, or silver nitrate in the presence of ammonia solution). An acid is formed In the presence of water, an amide results when ammonia or an amine is used, and an ester is produced in the presence of an alcohol ... 

The third operation, involving the conversion of the diazo ketone into an acid or a simple derivative thereof, is known as the Wolif rearrangement. 

The diazo ketone 3, when treated with silver oxide as catalyst, decomposes into ketocarbene 5 and dinitrogen Na. This decomposition reaction can also be achieved by heating or by irradiation with uv-light. The ketocarbene undergoes a Wolff rearrangement to give a ketene 6 ... 

The ketocarbene 4 that is generated by loss of Na from the a-diazo ketone, and that has an electron-sextet, rearranges to the more stable ketene 2 by a nucleophilic 1,2-shift of substituent R. The ketene thus formed corresponds to the isocyanate product of the related Curtius reaction. The ketene can further react with nucleophilic agents, that add to the C=0-double bond. For example by reaction with water a carboxylic acid 3 is formed, while from reaction with an alcohol R -OH an ester 5 is obtained directly. The reaction with ammonia or an amine R -NHa leads to formation of a carboxylic amide 6 or 7 ... 

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

In this section we first discuss photolytic reactions of arenediazonium salts and report on quinone diazides at the end of the section in the context of imaging technology. Diazoalkenes, non-quinonoid diazo ketones, and the Wolff rearrangement are treated in the book on aliphatic diazo compounds (Zollinger, 1995, Chap. 8). 

The diazo ketone can exist in two conformations, called s-(E) and s-(Z). Studies have shown that Wolff rearrangement takes place preferentially from the s-(Z) conformation. 

Pyrolysis of carboxylic acids Dehydrohalogenation of acyl halides Dehalogenation of a-halo acyl halides Rearrangement of diazo ketones (Wolff)... 

There are several reactions that are conceptually related to carbene reactions but do not involve carbene, or even carbenoid, intermediates. Usually, these are reactions in which the generation of a carbene is circumvented by a concerted rearrangement process. Important examples of this type are the thermal and photochemical reactions of a-diazo ketones. When a-diazo ketones are decomposed thermally or photochemically, they usually rearrange to ketenes, in a reaction known as the Wolff rearrangement.232... 

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. 

The use of copper as a catalyst in carbenoid transfer has its roots in the Amdt-Eistert reaction, Eq. 1 (3). Although the original 1935 paper describes the Wolff rearrangement of a-diazo ketones to homologous carboxylic acids using silver, the authors mention that copper may be substituted in this reaction. In 1952, Yates (4) demonstrated that copper bronze induces insertion of diazo compounds into the X-H bond of alcohols, amines, and phenols without rearrangement, Eq. 2. Yates proposal of a distinct metal carbenoid intermediate formed the basis of the currently accepted mechanistic construct for the cyclopropanation reaction using diazo compounds. 

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