Diazo compounds ketones

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

Ring enlargement of benzene derivatives by carbenes generated from diazo compounds (better in the presence of a Rh catalyst) Conversion of aldehydes to ketones by diazo compounds (Schlotterbeck) see also Ptau Planer... 

On treatment with alkaline reagents, -toluenesulfonylhydra-zones of aldehydes and ketones yield diazo compounds which decompose in hydroxylic solvents to yield olefinic (or bicylic) compounds and in aprotic solvents to yield olefins and cyclo-propanes. ... 

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

Pyrido[],2-a]pyrimidine-3,7-dicarboxylate 396 was also obtained in the reaction of diazo compound 395 and methyl vinyl ketone in boiling benzene in the presence of a catalytic amount of ruthenium acetate. 

Photo-de-diazoniation has found relatively little application in organic synthesis, as is clearly evident from the annual Specialist Periodical Reports on Photochemistry published by the Royal Society of Chemistry. Since the beginning of these reports (1970) they have contained a section on the elimination of nitrogen from diazo compounds, written since 1973 by Reid (1990). In the 1980s (including 1990), at least 90% of each report is concerned with dediazoniations of diazoalkanes and non-quinon-oid diazo ketones, the rest being mainly related to quinone diazides and only occasionally to arenediazonium salts. 

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). 

Reaction with alcohols is general for diazo compounds, but it is most often performed with diazomethane to produce methyl ethers or with diazo ketones to produce ot-keto ethers, since these kinds of diazo compounds are most readily available. With diazomethane the method is expensive and requires great caution. It is used chiefly to methylate alcohols and phenols that are expensive or available in small amounts, since the conditions are mild and high yields are obtained. Hydroxy compounds react better as their acidity increases ordinary alcohols do not react at... 

The reaction has also been applied to compounds with other leaving groups. Diazo ketones, diazo esters, diazo nitriles, and diazo aldehydes react with trialkylboranes in a similar manner, for example. 

In contrast to aldehydes, simple ketones are poor substrates for Fe-catalyzed olefinations due to their weak electrophilicity. Decreasing the electron density of carbonyl group can facilitate olefination of ketones with diazo compounds. 

B. Ring expansion of cyclic ketones using diazo compounds... 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate 140), contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

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. 

The simple primary amines of the aliphatic series, then, do not form diazo-compounds because the reaction which would le, d to their formation only occurs at a temperature at which they are destroyed. The reactivity of the NH2-group can, however, be increased by a neighbouring carbonyl group. Thus we come to the case of the esters of the a-amino-carboxylic acids and of the a-amino-ketones. The ethyl ester of glycine can be diazotised even in the cold the diazo-compound which does not decompose under these conditions undergoes stabilisation by elimination of water and change into ethyl diazoacetate ... 

Acceptor-monosubstituted diazomethanes can be further converted into other types of diazo compound. C-Acylation of diazoacetic esters generally requires very reactive acylating agents, such as acid chlorides [969,970] or bromides [971]. C-Alkylations of acyldiazomethanes are best accomplished by metallation followed by treatment with a carbon electrophile [972-977], C-alkylation can also occur without any base if sufficiently electrophilic aldehydes or ketones are used [973,978 -982] or if the alkylation proceeds intramolecularly [983]. 

Reaction of carbonyl compounds with aliphatic diazo compounds to deliver homologated ketones. 

Non-functionalized aliphatic diazo compounds are fairly rare, and so are their reductions. Good examples of the reduction of diazo compounds to either amines or hydrazones are found with a-diazo ketones and a-diazo esters (pp. 124, 125, 160). 

In all of the examples cited in Section 1.2.2.3.2.3.1, the diazo compounds are arranged such that none has a 3-hydride available. It could be expected that if a simple a-diazo ketone with fi-C — H bonds were exposed to the rhodium catalyst, metallocarbene formation would proceed as usual, but that /S-hydride elimination would compete with the desired 1,5-insertion. Such a /3-hydride elimination could, in fact, be viewed as a 1,2-insertion, i.e., 1 to 2. 

A similar story attends the chemistry of cyclopropylcarbenes. In the 1960s it was shown that cyclopropyl methyl diazomethane gives almost exclusively the product of apparent carbon-carbon insertion. " Surely we are now suspicious, and rightly so, as neither photolysis of 62 nor deoxygenation of cyclopropyl methyl ketone reproduces these results. Instead, carbon-hydrogen insertion dominates (Scheme 7.25). Once again, a direct reaction of photoexcited diazo compound appears to be the dominant source of the product of ring expansion (carbon-carbon insertion). 

This general procedure is effective for the preparation of many types of phenylhydrazones. For example, a substituted diazo compound can be employed.2 Alkylated acetoacetic esters 8 and ethyl benzoylacetate 4 may be used. For the higher homologs, the a-formyl derivatives of ketones may be used in place of ethyl acetoacetate.6 6 Ethyl pyridylacetates may also be substituted for ethyl acetoacetate.7 The products in these cases are the phenylhydrazones of 2-acylpyridines. 

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