A-Diazoketone

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). 

The diazoketohe 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. 

D. Cyclic a-Diazoketones Ring-Contraction in Photolytic Wolff Rearrangements... 

The photolytic decomposition of a-diazoketones, accompanied by rearrangement to ketene (photolytic Wolff rearrangement), has been used successfully in the preparation of A-nor- and C-norsteroids. The method is reviewed in chapter 15 by R. M. Scribner. ... 

Photolysis of a-diazoketones has also been used to prepare A-norsteroids. Results in the A-nor series support the ketene intermediate invoked for the assignment of the 16) -configuration to the D-nor acids. Thus, irradiation of 2-diazo-5a-cholestan-3-one (99) gives 2/ -carboxy-A-nor-cholestane (100, R = H) in 45 % yield. ... 

Retropinacol rearrangement, 416 Ring contraction in photolytic cyclic a-diazoketones rearrangements, 316 12- p/-rockogenin mesylate, 400... 

Chloroximes and enamines have provided aminoisoxazolines which could readily be converted to isoxazoles with acid (610-612). Pyrrazoles were usually obtained from addition of chlorohydrazones to enamines (610,613). The intermediate aminopyrazolines could only be isolated from the reaction of the cyclopentenyl enamine system. Pyrazoles were also obtained from the reactions of enamines with a-diazoketones and a-diazoesters (614). 

In his investigations of strained bicycHc systems, Meinwald 4) has explored the photolytic rearrangement of a-diazoketones to carboxylic acids according to the reactions. The procedure given below is an example of this process, employing as the... 

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... 

The photolysis of cyclic a-diazoketones results in ring contraction to a ketene, which can be isolated as the corresponding ester. 

Finally, a nice combination of a light-induced Wolff reaction of a diazoketone (e. g., 5-108) with a thermal Cope rearrangement, a light-induced Norrish type I cleavage and a recombination was developed by Stoltz and coworkers (Scheme 5.22) [38]. Here, irradiation of 5-108 at 254 nm in a photoreactor afforded the bicy-... 

The domino reaction of a carbonylylide from a diazoketone followed by a 1,3-dipolar cycloaddition has also been investigated using rutbenium(II)porphyrins 6/2-39 as catalyst [196]. Moreover, Che and coworkers [197] have used the Ru-cata-... 

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 ... 

The reaction, formally speaking a [3 + 2] cycloaddition between the aldehyde and a ketocarbene, resembles the dihydrofuran formation from 57 a or similar a-diazoketones and alkenes (see Sect. 2.3.1). For that reaction type, 2-diazo-l,3-dicarbonyl compounds and ethyl diazopyruvate 56 were found to be suited equally well. This similarity pertains also to the reactivity towards carbonyl functions 1,3-dioxole-4-carboxylates are also obtained by copper chelate catalyzed decomposition of 56 in the presence of aliphatic and aromatic aldehydes as well as enolizable ketones 276). No such products were reported for the catalyzed decomposition of ethyl diazoacetate in the presence of the same ketones 271,272). The reasons for the different reactivity of ethoxycarbonylcarbene and a-ketocarbenes (or the respective metal carbenes) have only been speculated upon so far 276). 

Intramolecular C/H insertion by copper-catalyzed decomposition of a-diazoketones provides a convenient cyclization procedure which is limited, however, to diazo compounds which allow energetically favorable realization of the transition state leading to the cyclized product. 

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. 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Metal-catalyzed decomposition of p,y-unsaturated a -diazoketones 400 in the presence of an alcohol affords rearranged y,8-unsaturated esters 407 this process has been termed the vinylogous Wolff rearrangement193 . Full accounts dealing with the... 

The intramolecular addition of alkynyl-substituted a-diazoketones is catalyzed by Rh2(OAc)4 to give transient cyclopropenes, which spontaneously rearrange to vinylogous a-keto carbene intermediates for further carbon-skeleton transformations [54]. 

Two type la syntheses of (3-hydroxypyrroles have appeared. An aza-Nazarov cyclization of l-azapenta-l,4-dien-3-ones produced (3-hydroxypyrroles including 2,2 -bipyrroles <06EJO5339>. A second approach to a (3-hydroxypyrrole involved an intramolecular N-H insertion into a rhodium carbene derived from the decomposition of a diazoketone <06JOC5560>. On the other hand, the photochemical decomposition of the diazoketone led to pyrrolidin-2-ones. 

Abstract Diazonium salts have been previously used to cleave DNA via generation of carbon centered radicals and cations. Efforts have been made in the past decade or so to develop diazo compounds and a-diazoketones for physiologically relevant DNA cleavage. These efforts, coupled with their relevance to the mechanism of action of kinamycin and lomaiviticin antibiotics and other naturally occurring diazo compounds, will be discussed. 

Fig. 16 a-Diazoketones for the generation of neocarzinostatin radical chromophore under photolytic conditions... 

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