A-diazo carbonyl compound

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Preparation of a-DiAzo Carbonyl Compounds via Phase Transfer Catalysis ... 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

Scheme 6.17 Intramolecular cyclopropanations of a-nitro-a-diazo carbonyl compounds.

The overall reaction is reminiscent of the Wolff rearrangement of a-diazo carbonyl compounds which gives ketenes. Compounds 6 formally represent their phosphorus analogues and are sometimes also designated as phosphenes 11... 

Addition of diazomethane to cyanoallene took place at the internal C=C bond of the cyanoallene to give 4-methylenepyrazoline 85. The following isomerization via 1,3-hydrogen shifts afforded 4-methyl-5-cyanopyrazole 86 [83], a-Diazo carbonyl compounds reacted in an analogous way [84]. 

Only a few methods are available for the synthesis of isomilnchnones, and the original techniques are summarized by Gingrich and Baum (10). Padwa and coworkers (25) provided a more recent historical account of the synthesis of isomilnchnones. The major new development is the generation of isomilnchnones using the rhodium(II)-catalyzed decomposition of a-diazo carbonyl compounds. In continuation of earlier work (28), Haddadin and Tannus (29) extended their new synthesis of isomilnchnones 51 from A(-benzoylphenylglyoxanilides (50) as illustrated in Scheme 10.6 to a series of new compounds. 

Doyle et al. (34) were the first group to generate isomiinchnones from diazo imides using Rh(II) catalysis. For example, isomiinchnone 60 was produced from diazo imide 59, but attempts to trap this species with ethyl acrylate were unsuccessful. The only material identified was the isomiinchnone hydrolysis product. This use of Rh(II) to generate a rhodium-carbenoid species from an a-diazo carbonyl compound is reminiscent of the first successful synthesis of... 

Sulfonium ylides generated through base-promoted deprotonation of sulfonium salt have been extensively studied. The reaction of sulfides with a diazo carbonyl compound in the presence of a transition metal catalyst is an alternative approach to obtain sulfonium ylides. Sulfonium ylides are more stable than the corresponding oxonium ylides. Stable sulfonium ylides generated by the reaction of an Rh(ii) carbene complex with thiophene have been reported (Figure 5). ... 

Oxepanes and oxocanes.5 These seven- and eight-membered ring ethers can be obtained by cyclization of a-diazo carbonyl compounds induced with Rh2(OAc)4. Examples ... 

Rearrangement of jS-thio-a-diazo carbonyl compounds (44) occurred upon decomposition of the diazo function by metals, especially Rh(II).43 1,2-Thio migration adducts (45) were obtained with moderate to high diastereoselectivities. The outcome of the decomposition of (46) by Rh(II) was shown to be highly dependent on the nature of the X substituent.44 When X = OH, (47) has been exclusively observed, whereas (48) was the only product isolated when X = NHC(0)CC13. 

T. Ye, M. A. McKervey, Organic Synthesis with a-Diazo Carbonyl Compounds, Chem. Rev. 1994, 94, 1091-1160. 

A. Padwa, D. J. Austin, Ligand Effects on the Chemoselectivity of Transition Metal Catalyzed Reactions of a-Diazo Carbonyl Compounds, Angew. Chem. Int. Ed. Engl. 1994, 33, 801-811. 

In the photochemistry of a-diazo carbonyl compounds, singlet carbenes undergo a Wolff rearrangement while triplet carbenes react with alkenes to afford cydopropanes. 

C—C—O+N—C. a-Hydroxy ketones react with monosubstituted cyanamides under the influence of sodium hydroxide to yield derivatives of 2-aminooxazole (equation 125) (76S591). Oxazoles are obtained by the action of nitriles on a-diazo carbonyl compounds in the presence of Lewis acids, such as aluminum chloride or boron trifluoride, and the reaction is thought to involve the intermediacy of nitrilium salts (equation 126). Nitrilium salts are also the effective agents in the formation of oxazoles from a-chloro ketones and nitriles in the presence of tin(IV) chloride (equation 127). 

Treatment of thioketone 635 with a-diazo carbonyl compounds in the presence of Rh2(OAc)4 gives 3-aminothio-phenes 637. Condensation of the ketene acetal with carbenoids, derived from diazo compounds, produces the intermediates 636, which undergo an intramolecular cyclization and subsequent aromatization to afford 637 (Scheme 95) <2002J(P1)2414, 20020L873>. 

Cyclopropyl carbonyl compounds, SbF, promotes condensation of a, -enones with a-diazo carbonyl compounds to form 1,2-disubstituted cyclopropyl carbonyl compounds. BF3 etherate or TiF4 is much less efficient. The reaction is subject to steric hindrance by substituents on the vinyl group. SbFs also promotes isomerization of the initial trans-cis mixture of products to the more stable isomer. ... 

Meier, H., Zeller, K. P. Wolff rearrangement of a-diazo carbonyl compounds. Arrgew. Chem. 1975, 87, 52-63. 

Calvo-Losada, S., Quirante, J. J. DFT study of competitive Wolff rearrangement and [1,2]-hydrogen shift of P-oxy-a-diazo carbonyl compounds. THEOCHEM1997, 398-399,435 43. 

The great majority of intramolecular cyclopropanation reactions of unsaturated a-diazo-carbonyl compounds have been achieved with copper catalysts, especially with copper powder or copper bronze, copper(II) sulfate, and bis(acetylacetonato)copper(II). Homogeneous catalysis by bis(salicylaldimato)copper(II) or copper(I) halide/trialkyl phosphite complexes has repeatedly been reported to be superior to heterogeneous catalysis by other copper(I) and cop-per(II) salts, e.g. formation of and 2. ... 

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

An example is illustrated in Scheme 67. The sequence can be performed directly on amino-modified resin without a special linker unit. a-Diazo carbonyl compounds of type 140 were reacted wifh an Rh(II) catalyst to form highly reactive Rh(II) carbenoids, which yielded isomiinchnones 141. These underwent [2-1-3] cycloadditions wifh alkynes to form bicyclic intermediates 142. Thermolytic cycloreversion led to fhe desired furans 143 in high purity [163, 164]. 

There has been continued interest in the synthesis of oxazoles from a-diazo carbonyl compounds and nitriles catalyzed by Lewis acids. The BFa-catalyzed reaction of a-diazoacetophenones or methyl p-nitrophenyldiazoacetate with chloroacetonitrile affords 5-aryl-2-chloromethyloxazoles or 2-chloromethyl-5-methoxy-4-(p-nitrophenyl)oxazole, respectively (Equation (19)) <89BCJ618>. The former products react with primary, secondary, and tertiary amines by nucleophilic displacement of the chloride group. Methyl or ethyl isocyanate may be used as the nitrile component to prepare... 

Tomioka, H., Okuno, H., Izawa, Y., Mechanism of the Photochemical Wolff Rearrangement The Role of Conformation in the Photolysis of a Diazo Carbonyl Compounds, J. Org. Chem. 1980, 45, 5278 5283. 

Another efficient method to obtain metal carbenoid species is by treating diazo compounds with catalytic amounts of transition metals (see preceding two papers) [22, 23, 24]. Although a-diazo carbonyl compounds [23] are very useful precursors for this transformation, alkyl- or aryl-substituted diazo compounds can be also used [24,25]. The most effective catalysts for this reaction are rhodium and copper based, but several other transition metals, possessing a vacant... 

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