Diazoketones synthesis

The diazoketone synthesis for the preparation of 21-methyl-20-keto steroids has been discussed earlier. 21-Oxygenated derivatives can also be prepared by this route simply by reacting the diazoketone with an appropriate acid-nucleophile combination. For example, reaction of a diazoketone with acetic acid leads to the 21-acetate and boron trifluoride in the presence of methanol affords the 21-methyl ether.299... 

Duddeck, H., Ferguson, G., Kaitner, B., Kennedy, M., McKervey, M. A., Maguire, A. R. The intramolecular Buchner reaction of aryl diazoketones. Synthesis and x-ray crystai structures of some poiyfunctionai hydroazuiene iactones. J. Chem. Soc., Perkin Trans. 11990, 1055-1063. 

Rearrangement of a-diazoketones. Synthesis of cyclopropanes by copper-catalyzed decomposition of a-diazoketones has been a useful reaction, particularly as a route to natural products (2, 82-84 3, 63-65, 69-71 4, 103). 

Forster Diazoketone Synthesis Forster Reaction Four-Component Condensation Franchimont Reaction Frankland Synthesis Frankland-Duppa Reaction Freund Reaction... 

A variation of Hantzsch s synthesis, using thioureas in conjunction with a-diazoketones in place of a-halogenoketones, has proved to be generally applicable. In this manner, King and MUler (310) obtained 2-amino-4-phenylthiazole in 67% yield. A wide range of 4-substituted 2-aIkyl (or aryl) aminothiazoles and 2-arylimino-3,4-diarylthiazolines have been prepared by Hampel and Muller (627, 665, 666). 

Tandem cyclization-cycloaddition of diazoketones in the synthesis of some alkaloids 97F303. 

Diazocarbonyl compounds are especially useful in these reactions because of their ease of formation, relative stability, and controlled reactivity in catalytic reactions [ 1,11 ]. As outlined in Scheme 1, a wide diversity of methodologies are available for this synthesis, with access dependent on the nature of Z. Vinyl- and aryldiazoacetates are accessible by other pathways [2]. The order of reactivity toward diazo decomposition has diazoketones and diazoacetates much more reactive than diazoacetoacetates or diazomalonates. However, the influence of electronic effects on reactivities is more pronounced with phenyl- and vinyl-diazoacetates than with diazoacetoacetates and, especially, diazoacetates [12]. 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis,Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition metals have also been used. Microwave irradiation has been used to facilitate this reaction. Aniline derivatives react with a-diazoketones, in the presence of a... 

Yanez et al. reported the synthesis of miconazole and analogs through a carbenoid intermediate. The process involves the intermolecular insertion of carbe-noid species to imidazole from a-diazoketones with copper acetylacetonate as the key reaction of the synthetic route [11]. 

The synthesis of cycloheptatrienyl ketones 233 from benzene and a-diazoketones 232 proceeds in essentially quantitative yield the products were not isolated but directly transformed into benzyl ketones 234 through the action of trifluoroacetic acid 229 ... 

An interesting application of carbenoid O/H insertion is the synthesis of macrocyclic oxacrown ethers 337 from a,a>-diazoketones 336 and oligoethylene glycols 323). 

The known examples of carbenoid insertion into an S—H bond have been supplemented by the Rh2(OAc)4-catalyzed synthesis of a-phenylthioketones from a-diazoketones and thiophenol 327). By this method, a number of primary and secondary acyclic a-diazoketones, ethyl diazoacetate and cyclic diazoketones such as 2-diazocyclopentanone, 2-diazo-6-methylcyclohexanone and 2-diazocyclohepta-none were converted at room temperature in good to high yield. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

The synthesis of /Mactams from diazoketones and imines can be realized not only by using photochemical reaction conditions but also under the action of microwave irradiation. When the reaction was performed in o-dichlorobenzene at 180 °C, however, the rates of thermal and microwave-assisted formations of -lactams were shown to be identical within the limits of experimental error (80-85% conversion after 5 min) [30]. 

The use of thiocarbonyl compounds and also trimethylsilyldiazomethane in the Pechmann-Nold synthesis has greatly increased the scope of this reaction in recent years. Wolff s synthesis has also benefited from advances in the synthesis of both diazoketones and thionating reagents. 

Ketocarbenes generated from diazoketones give two main type of reactions. The first one is the conventional carbene reaction, i.e. intramolecular insertion into a C—H or C—C bond, as applied in the synthesis of a... 

Several reviews of P-lactam chemistry have appeared including a general survey with 407 references <99MI335>. Other reviews include discussions of thioester enolate-imine reactions , enantio- and diastereo-selective routes to azetidinones <99MI221>, the use of diazoketones in diastereoselective synthesis <99MI43>, and solid-phase and combinatorial syntheses of p-lactams <99MI955>. 

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