1- Diazo-2-butanone

Intramolecular cyclopropanation of 4-aryl-1 -diazo-2-butanones 240 allows construction of the bicyclo[5.3.0]decane framework 12). In a reaction sequence analogous to that described above for the intermolecular ketocarbenoid reaction, bicyclo-[5.3.0]deca-l,3,5-trien-8-ones 241 are formed. They rearrange to the conjugated isomers 242 at the high temperatures needed if the reaction is catalyzed by copper 2311 or CuCl 232), but can be isolated in excellent yield from the Rh2(OAc)4-promoted reaction which occurs at lower temperature 233... 

The comparison between the cycloaddition behavior of simple diazoketones and of ethyl diazopyruvate 56 towards the same olefin underlines the crucial influence of the ethoxycarbonyl group attached to the carbonyl function. This becomes once again evident when COOEt is replaced by an acetal function, such as in l-diazo-3,3-di-methoxy-2-butanone 86 with enol ethers and acetates, cyclopropanes rather than dihydrofurans are now obtained 113). ... 

Easily available copper(II) tartrate has also been used for an enantioselective cyclopropanation. From 3-methoxystyrene and 4-bromo-l-diazo-2-butanone, the cyclopropanes cis/trans-204 were obtained the mainly formed frans-isomer displayed an enantiomeric excess of 46% i99>. This reaction constituted the opening step of asymmetric total syntheses of equilenin and estrone. 

In an intramolecular version of ketocarbenoid a-C/H insertion, copper-promoted decomposition of l-diazo-3-(pyrrol-l-yl)-2-propanone (258a) or l-diazo-4-(pyrrol-l-yl)-2-butanone (258b) resulted in quantitative formation of the respective cycli-zation product 259 242 >. The cyclization 260 -> 261, on the other hand, is a low-yield reaction which is accompanied by olefin formation. The product ratio was found to vary with the copper catalyst used, but the total yield never exceeded 35 % 243>. 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

A. 1-Diazo-4-phenyl-2-butanone. A 1-L Erlenmeyer flask equipped with a two-inch magnetic stirring bar and a two-hole rubber stopper fitted with a 125-mL Teflon stopcock separatory funnel (Note 2 and a drying tube filled with potassium hydroxide (Note 3) is charged with a solution of 200 mmol (3.4 equiv) of diazomethane (Note 4) in 600 mL of dry ether. The solution is cooled to 0°C and stirred at high speed (Note 5). To this cooled solution, 10.0 g (59 mmol) of hydrocinnamoyl chloride (3-phenylpropionyl chloride) (Note 6) diluted to 125 mL with anhydrous ether is added dropwise over a 1 -hr period. The resulting reaction mixture is stirred cold for an additional 0.5 hr and then at room temperature for 1 hr. After this period of time the... 

A pure sample of diazo ketone can be obtained by chromatography on silica gel using 15% ethyl acetate/hexane as an eluent, Rf = 0.37. The checkers estimate the purity of the crude diazo ketone to be 90-91% based on careful column chromatography of 1 0-g aliquots. They further estimate that approximately 5-6% of 1 -chloro-4-phenyl-2-butanone is also produced in the reaction. The spectral properties of 1-diazo-4-phenyl-2-butanone are as follows 1H NMR (300 MHz, CDCI3) 8 2.59-2.64 (m, 2 H), 2.95 (t, 2 H, J = 7) 5.20 (broad s, 1 H), 7.17-7.31 (m, 5 H). 

The checkers found that on this scale a bulb-to-bulb (Kugelrohr) distillation could also be employed. The distilled product is contaminated with approximately 4-5% of 1 -chloro-4-phenyl-2-butanone which was produced in Step A. This impurity is easily removed by recrystallization from hexane. Alternatively, this impurity can be removed at the diazo ketone stage by column chromatography. The use of purified diazo ketone in Step B affords purer distilled product, but this modification has no significant effect on the overall yield. 

Diazo-4-phenyl-2-butanone 2-Butanone, 1 -diazo-4-pihenyl- (8,9) (10290-42-3) Diazomethane Methane, diazo- (8,9) (334-88-3)... 

These findings are not surprising since the alpha carbon atoms of these diazo compounds carry an aromatic ring. However, it has been observed recently by Dahn et al. [210] that solvent isotope effects are larger than 1 in the acid catalyzed hydrolyses of various secondary diazoketones (such as 3-diazo-2-butanone), ethyl a-diazopropionate, and l,l,l-trifluoro-2-diazopropane. Similar results have been obtained by Jugelt and Berseck... 

Similar conclusions may be drawn from a discussion of the reaction products. As the product ratios do not depend on [H30+], it is likely that all products are formed via a common intermediate. It is significant that alkenes are among the products of hydrolysis of 3-diazo-2-butanone and... 

The value of fef1 for the hydrolysis of diazoacetate ion is five powers of ten higher than that for the hydrolysis of 3-diazo-2-butanone (Table 17). Proton transfer is rate-determining in both cases. Part of the rate... 

Use of ethyl diazopyruvate or l-diazo-3,3-dimethoxy-2-butanone for cyclopropanation introduces additional functionality into the ring-opened products . j -Methylene y-butyrolactones result from bisalkoxycarbonyl-substituted cyclopropanes in three steps (equation 85) . ... 

Diketones Copper(I) acetylacetonate is a very effective copper catalyst for the insertion of an a-ketocarbene into C-C double bonds. Thus (3) can be obtained in 55% yield from the reaction of l-diazo-2-butanone (1) with isopropenyl acetate (2). When (3) is refluxed with 4% methanolic sodium hydroxide, 2,3-dimethylcyclo-pentene-2-one (5) is obtained in 85% yield. 

Reaction with st-diazoketones.1 DMAD reacts with 2-diazo-3-butanone (1) to give the N-acetylpyrazole (2). The reagent reacts with 2-diazocycIopentanone (3) to form (4), dimethyl 4,5-dihydro-7(6H)-oxopyrazoio[l,5-a]pyridine-2,3-dicarboxylate. 

Interestingly, 0,7-unsaturated a-diazoketones are also sources of cyclo-butanones when they are exposed to protic acid.1 For example, compound XI furnished XII in high yield upon contact with concentrated sulfuric acid (see Scheme 42.3). In a conceptually analogous reaction, /3,7-unsaturated a-diazo-ketones proved to be useful in the construction of cyclopentanones XIV1 in a polyolefinic cationic cyclization process reminiscent of the mechanism by which plants in nature build their polycyclic triterpenoid metabolites from squalene, that is, XV - XVI.12... 

The condensation of l-chloro-3-diazopiopanone (57) with aldehydes provides epoxy diazo ketones (equation 18). Treatment of a methanolic solution of (57) and benzaldehyde, in a stoichiometric ratio, with aqueous sodium hydroxide furnishes l-diazo-3,4-epoxy-4-phenyl-2-butanone (59a) in 69% yield the rrans-epoxide is obtained stereoselectively, analogous to the Darzens condensation of benzaldehyde and chloroacetone. The reaction is reported to proceed to give also the diazo ketones (59b-59e), and the epoxides obtained are exclusively of the trans configuration. ... 

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