Diazocarbonyl compounds preparation

The most frequent synthetic approaches, summarized in Scheme 4, are towards the primary photophores. The preparation of aryl azide derivatives follows the typical retro-synthetic pathway in the majority of the reported cases (Scheme 4 A), and, practically, diazotation is the most commonly used procedure [24 - 29]. In the case of diazirines only one major synthetic sequence is repeated ammonolysis of oximes followed by dehydrogenation (Scheme 4B) [30-32]. There are various ways of preparing diazo- or diazocarbonyl-compounds most frequently the Forster and Bamford-Stevens reactions (Scheme 4C) are employed [33-37]. 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

Carbonyl ylides can be viewed as an adduct between a carbonyl group and a carbene and, in fact, some ylides have been prepared this way (see above). The application of carbonyl ylides to the synthesis of complex natural products has been greatly advanced by the finding that stabilized carbenoids can be generated by the decomposition of ot-diazocarbonyl compounds with copper and rhodium complexes. The metallocarbenoids formed by this method are highly electrophilic on carbon and readily add nucleophiles such as the oxygen of many carbonyl derivatives to form carbonyl ylides. This type of reaction is in fact quite old with the first report being the addition of diazomalonate and benzaldehyde (33,34). 

Diazocarbonyl compounds are optimum for these transformations, and they may be readily prepared by a variety of methods. The use of iodonium ylides (17) has also been developed, " but they exhibit no obvious advantage for selectivity in carbene-transfer reactions. Enantioselection is much higher with diazoacetates than with diazoacetoacetates (18). 

Diazocarbonyl compounds can be prepared on insoluble supports by diazo group transfer with sulfonyl azides or by diazotization of primary amines. Diazo group transfer from sulfonyl azides to 1,3-dicarbonyl compounds proceeds on cross-linked polystyrene as smoothly as in solution (Table 10.19). When 3-keto esters or amides are... 

Diazocarbonyl compounds can also be prepared by C-acylation of diazoalkanes with polystyrene-bound acyl halides (Entry 6, Table 10.19). As an alternative to diazomethane, the more stable a-(trimethylsilyl)diazomethane may be used, which is sufficiently nucleophilic to react with acyl halides. On heating, the resulting a-(trimethyl-silyl)diazo ketones undergo Wolff rearrangement to yield ketenes, and have also been used as starting materials for the preparation of oxazoles [368]. 

Rhodium acetate catalyzed cyclopropanation of methylenecycloalkanes with diazocarbonyl compounds (equation 9) provides a direct method for preparation of functionalized SPC27. 

Although the transition-metal-catalyzed reaction of a-diazocarbonyl compounds with aromatic molecules has received much attention in recent years,104 the metal-catalyzed behavior of these compounds with N-containing heteroaromatics has not been extensively studied. An early example involved the preparation of isoquinoline-carboethoxymethylide... 

The same salt from acetylene afforded similarly adducts with furan and 1,3-diphenyl i sobenzofuran. A number of alkynyl iodonium salts underwent also [2 + 3] cycloaddition with dipolarophiles such as a-diazocarbonyl compounds, nitrile oxides, etc., allowing the preparation of iodonium salts with an alkenyl or a heterocyclic moiety [7],... 

Diazo compounds have also been used as precursors in the preparation of pyrazoles and indazoles. The copper-promoted cycloaddition reaction of lithium acetylides 18 with diazocarbonyl compounds 19 provided a direct and efficient approach to the synthesis of pyrazoles 20 <07AG(I)3242>. A facile, efficient, and general method for the synthesis of 1-arylated indazoles 22 and A-unsubstituted indazoles 23 by the 1,3-dipolar cycloaddition of benzynes, generated from 21, with diazomethane derivatives has been reported <07AG(I)3323>. Reaction of diazo(trimethylsilyl)methylmagnesium bromide with aldehydes or ketones gave 2-diazo-2-(trimethylsilyl)ethanols, which were applied to the synthesis of di- and trisubstituted pyrazoles via [3+2] cycloaddition reaction with ethyl propiolate or dimethyl acetylenedicarboxylate <07S3371>. 

The a-diazocarbonyl derivatives used in these studies are easily prepared, and the rhodium-mediated cyclizations proceed rapidly, with high catalyst turnover (ca. 100-1000). The catalysts are stable at room temperature for years, and are not air sensitive. The reactions work best in inert solvents such as dichlor-omethane or benzene, and the solvent must be dry. Slow addition of the diazocarbonyl compound to the catalyst is not usually necessary. 

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocarbonyl compounds, there are fewer applications of diazomethane as a carbenoid precursor. Catalytic decomposition of diazomethane, CH2N2, has been reported as a general method for the methylenation of chemical compounds [12]. The efficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is poor. The preparative use of diazomethane in the synthesis of cyclopropane derivatives from olefins is mostly associated with the employment of palladium cat-... 

Alloum, A.B., and Villemin, D., Potassium fluoride on alumina. An easy preparation of diazocarbonyl compounds, Synth. Commun., 19, 2567, 1989. 

The most versatile carbene precursors are a-diazocarbonyl compounds such as diazoacetic acid esters because they are readily prepared, easy to handle and much more stable than ordinary diazoalkanes [10,38]. Nevertheless, one should always be aware of the potential hazards of diazo compounds in general [39],but if the necessary precautions are taken, they can be safely handled even on an industrial scale [18]. The most frequently used reagent is commercially available ethyl diazoacetate. Besides a-diazocarbonyl reagents, diazomethane [40,41 ] and a y-diazoacrylate derivative [42] have been used in enantioselective Cu-cata-lyzed cyclopropanations but the scope of these reactions has not been studied systematically. It has been shown in certain cases that diazo compounds can be replaced by other carbene precursors such as iodonium ylides, sulfonium yUdes, or lithiated sulfones [8,43],but successful applications of these reagents in enantioselective Cu-catalyzed reactions have not been reported yet. 

The catalytic transfer of carbenes to imines (Fig. 4) represents a method for the preparation of aziridines complementary to the imido transfer strategies summarized above. The synthetic accessibility of imines and diazocarbonyl compounds, combined with the relative cleanliness of diazo chemistry and the inherent convergence associated with the coupling of two potentially complex reaction partners offer considerable incentive for developing this approach. 

Reactions of a-diazocarbonyl compounds,halogen-substituted enolates and sulfur ylides with trialkylboranes were subsequently recorded and represent alternative methods of preparation (Scheme 3). 

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