Diazoacetoacetates

Benzoylphenyidiazomethane 2 Butan-l-yl diazoacetate t-Butyl diazoacetate t-Butyl-2-diazoacetoacetate Diazoacetonitrile 2-Diazocyclohexanone Diazocyclopentadiene 1 -Diazoindine... 

Diazocarbonyl compounds are especially useful in these reactions because of their ease of formation, relative stability, and controlled reactivity in catalytic reactions [ 1,11 ]. As outlined in Scheme 1, a wide diversity of methodologies are available for this synthesis, with access dependent on the nature of Z. Vinyl- and aryldiazoacetates are accessible by other pathways [2]. The order of reactivity toward diazo decomposition has diazoketones and diazoacetates much more reactive than diazoacetoacetates or diazomalonates. However, the influence of electronic effects on reactivities is more pronounced with phenyl- and vinyl-diazoacetates than with diazoacetoacetates and, especially, diazoacetates [12]. 

The synthesis of substituted 3,4-dihydrothiopyrans by the reaction of 2-amino-4,5-dihydrothiophene-3-carbonitriles with ethyl diazoacetoacetate involves rearrangement of initially formed 1,4-oxathiocines <96LA725>. 

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. 

Ethyl 2-diazoacetoacetate, 59, 69 Ethylene, 58, 73 Ethylene bromide, 55, 94 Ethylene carbonate, 58, 97... 

Rh2(OAc)4 has become the catalyst of choice for insertion of carbene moieties into the N—H bond of (3-lactams. Two cases of intermolecular reaction have been reported. The carbene unit derived from alkyl aryldiazoacetates 322 seems to be inserted only into the ring N—H bond of 323 246). Similarly, N-malonyl- 3-lactams 327 are available from diazomalonic esters 325 and (3-lactams 326 297). If, however, the acetate function in 326 is replaced by an alkylthio or arylthio group, C/S insertion rather than N/H insertion takes place (see Sect. 7.2). Reaction of ethyl diazoacetoacetate 57b with 328 also yields an N/H insertion product (329) 298>, rather than ethyl l-aza-4-oxa-3-methyl-7-oxabicyclo[3.2.0]hex-2-ene-2-earboxylate, as had been claimed before 299). 

C. t-Butyl diazoacetate. Into a 1-1. three-necked flask fitted with a stirrer, a dropping funnel, and a thermometer is placed a solution of 92.6 (0.50 mole) of /-butyl a-diazoacetoacetate in 150 ml. of methanol. After this solution has been cooled to 2-3° in an ice bath, a solution of sodium methoxide, prepared from 11.5 g. (0.50 g. atom) of sodium and 150 ml. of methanol, is added dropwise with stirring at such a rate that the reaction mixture remains within the temperature range 0-5° (about 30 minutes is required for the addition). After the addition is completed, the mixture is stirred in the ice bath for an additional 30 minutes. The red reaction solution is poured into 11. of ice water, and the resulting mixture is extracted with 500 ml. of ether. The aqueous phase is saturated with sodium chloride and extracted with two 500-ml. portions of ether (Note 8). The combined ethereal extracts are washed with 500 ml. of water and dried over anhydrous sodium sulfate. After the mixture has been filtered and the residue has been washed with ether, the bulk of the solvent... 

When a solution of the ester (155 R = H) in dioxan is warmed at 80 °C, the phosphonate (156) is produced together with about 5% yields of each of dimethyl hydrogen phosphonate and diazoacetoacetic ester (Scheme 8) the enol phosphate (157) could not be detected. The explanation for this sequence of reactions also relies on proton mobility, and the reaction is known to be acid-catalysed.124... 

Buten-l-yl diazoacetate, 2377 tert-Butyl diazoacetate, 2423 tert-Butyl 2-diazoacetoacetate, 3009 5-/er/-Butyl-3-diazo-3//-pyrazole, 2831 Cyanodiazoacetyl azide, 1346 5-Cyano-4-diazo-4//-l,2,3-triazole, 1345 Diazoacetaldehyde, 0710 Diazoacetonitrile, 0675 Diazoacetyl azide, 0679... 

Rhodium(II) catalyzed the addition of the carbene formed from methyl diazoacetoacetate, to the oxathiazolone (112 R = 4-MeOQH4) gives the 1,4,3-oxathiazine derivative (113) in low yield (6%), this probably proceeds through the intermediate sulfonium ylide (114), by decarboxylation and ring closure, either concominantly or sequentially (Scheme 14) <90JCR(S)343>. 

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). 

A similar carbenoid route to the fused /Mactam 5 involves reaction of ethyl diazoacetoacetate with 4-acctoxyazetidin-2-one (4) catalyzed by rhodium(II) acetate. Rhodium(II) acetate may also promote the cyclizalion step.6 For another route to compounds related to 5 see 8, 36. 37. 

Rhodium(II) catalyzed decomposition of ethyl diazoacetoacetate in thiophene gave no ylide, but only the 2-substituted product (67%) and the cyclopropane (mixture of stereoisomers) (79JCS(Pl)2624). 

A mixture of DL-threonine and DL-allothreonine was prepared by the hydrogenation of ethyl diazoacetoacetate over paltinum oxide in 70% ethanol containing sulfuric acid (eq. 9.90). 2,4-Dimethylpyrrole-3,5-dicarboxylic acid diethyl ester was also obtained as a byproduct. 

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