Diazo compounds carbonyl

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 reactivity of diazo carbonyl compounds appears to be related to the conformational equilibria between s-cis and s-trans conformations. A concerted rearrangement is favored by the s-cis conformation.237 The /-butyl compound 19, which exists in the s-trans conformation, gives very little di-/-butylketene on photolysis.238 A similarly... 

In a flash photolysis study of a series of diazo carbonyl compounds, a correlation was found between the amount of carbene that could be trapped by pyridine and the amount of s-trans ketone.240... 

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]. 

The ability to produce 1,3-dipoles, through the rhodium-catalyzed decomposition of diazo carbonyl compounds, provides unique opportunities for the accomplishment of a variety of cycloaddition reactions, in both an intra- and intermolecular sense. These transformations are often highly regio- and diastereoselective, making them extremely powerful tools for synthetic chemistry. This is exemplified in the number of applications of this chemistry to the construction of heterocyclic and natural-product ring systems. Future developments are likely to focus on the enantioselective and combinatorial variants of these reactions. 

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... 

Similar conclusions concerning the photochemistry of diazo carbonyl compounds and diazirines have been reached using similar experiments and logic. 

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 ... 

Intramolecular cyclopropanation reactions of alkenyl diazo carbonyl compounds are among the most useful catalytic metal carbene transformations, and the diversity of their applications for organic syntheses is substantial [7,10,24,84]. Their catalytic asymmetric reactions, however, have only recently been reported. An early application of the Aratani catalyst 2 (A = PhCH2) to... 

As may now be expected from Cu(II) compounds, whose reduction to Cu(I) is a requirement for catalyst activation, product yield and enantioselectivity depend on the reagents and conditions used. Other diazo carbonyl compounds, including a (J-keto-a-diazo esters and oc-diazo esters, underwent intramolecular cyclopropanation in moderate-to-good yields, but with low enantiocontrol. 

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. 

The success achieved with the Rh(II)-catalyzed transformations of -oximino diazo carbonyl compounds prompted our group to study some additional systems where the C-N 7i-bond was configurationally locked so that azomethine ylide formation would readily occur. Toward this end, we investigated the Rh(II)-catalyzed behavior of isoxazoline 186 in the presence of DMAD. This reaction afforded the azomethine-derived cycloadduct 187 as a 4 1 mixture of diastereomers in 65% yield. A similar transformation occurred using the a-diazoacetophenone derivative 188 which produced isoxazolo[3,2-a]isoquinoline 189 as a 2 1 mixture of diastereomers in 82% yield.84... 

J. Adams, D. M. Spero, Rhodium(II) Catalyzed Reactions of Diazo-Carbonyl Compounds, Tetrahedron 1991, 47, 1765-1808. 

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. 

More recently, Pfaltz has reported high enantioselectivities for the cyclopropanation of monosubstituted alkenes and dienes with diazo carbonyl compounds using chiral (semicorrinato)copper complexes (P-Cu) (23-25), and Evans, Masamune, and Pfaltz subsequently discovered exceptional enantioselectivities in intermolecular cyclopropanation reactions with the analogous bis-oxazoline copper complexes (26-28). With the exception of the chiral (camphorquinone dioximato)cobalt(II) catalysts (N-Co) reported by Nakamura and coworkers (29,30), whose reactivities and selectivities differ considerably from copper catalysts, chiral complexes of metals other than copper have not exhibited similar promise for high optical yields in cyclopropanation reactions (37). 

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>. 

Boron enolatcs 6, which arc also used as activated derivatives of carbonyl sub-strates, " can be similarly obtained from silyl enolethers 4, - or from diazo-carbonyl compounds 7 (Fig. 7), as well as from a, P-unsaturated ketones. - ... 

Diazo-carbonyl compounds as starting material for Mannich synthesis. 

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. ... 

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