Ethyl diazoacetate reactions with ketones

Within the framework of the above methodology, 2-methylenedioxole 554 is accessible by trapping a carbene with ketene 555 (77JOM155). Ethyl diazoacetate reacts with substituted cyclohexanones in the presence of Cu(acac)2 in a similar manner to produce spirodioxoles 556 (80JHC721), while the reaction of ethyl diazopyruvate with ketone 557 furnishes the 1 2 adduct 558 [88CI(L)631],... 

As it is known from experience that the metal carbenes operating in most catalyzed reactions of diazo compounds are electrophilic species, it comes as no surprise that only a few examples of efficient catalyzed cyclopropanation of electron-poor alkeiies exist. One of those examples is the copper-catalyzed cyclopropanation of methyl vinyl ketone with ethyl diazoacetate contrasting with the 2-pyrazoline formation in the purely thermal reaction (for failures to obtain cyclopropanes by copper-catalyzed decomposition of diazoesters, see Table VIII in Ref. 6). 

When unsymmetrical ketones were used in this reaction (with BF3 as catalyst), the less highly substituted carbon preferentially migrated. The reaction can be made regioselective by applying this method to the a-halo ketone, in which case only the other carbon migrates. The ethyl diazoacetate procedure has also been applied to the acetals or ketals of a, P-unsaturated aldehydes and ketones. ... 

Palladium(II) acetate was found to be a good catalyst for such cyclopropanations with ethyl diazoacetate (Scheme 19) by analogy with the same transformation using diazomethane (see Sect. 2.1). The best yields were obtained with monosubstituted alkenes such as acrylic esters and methyl vinyl ketone (64-85 %), whereas they dropped to 10-30% for a,p-unsaturated carbonyl compounds bearing alkyl groups in a- or p-position such as ethyl crotonate, isophorone and methyl methacrylate 141). In none of these reactions was formation of carbene dimers observed. 7>ms-benzalaceto-phenone was cyclopropanated stereospecifically in about 50% yield PdCl2 and palladium(II) acetylacetonate were less efficient catalysts 34 >. Diazoketones may be used instead of diazoesters, as the cyclopropanation of acrylonitrile by diazoacenaph-thenone/Pd(OAc)2 (75 % yield) shows142). 

Treatment of benzaldehydes with ethyl diazoacetate and a catalytic quantity of the iron Lewis acid [ -CpFe(CO)2(THF)]+BF4 yields the expected homologated ketone (80). However, the major product in most cases is the aryl-shifted structure (81a), predominantly as its enol tautomer, 3-hydroxy-2-arylacrylic acid (81b). This novel reaction occurs via a 1,2-aryl shift. Although the mechanism has not been fully characterized, there is evidence for loss of THF to give a vacancy for the aldehyde to bind to the iron, followed by diazoacetate attachment. The product balance is then determined by the ratio of 1,2-aryl to -hydride shift, with the former favoured by electron-donating substituents on the aryl ring. An alternative mechanism involving epoxide intermediates was ruled out by a control experiment. 

It has been shown that the lead tetraacetate-mediated 1,2-aryl shift of various meta-substituted / -cyclohexyl aryl ketones, e.g. (10), results in excellent yields of the corresponding rearranged esters (11). A unique reaction, providing 3-hydroxy-2-arylacrylic acid ethyl esters (14), has been observed between aryl aldehydes and ethyl diazoacetate in the presence of the iron Lewis acid [rj — (C5H5)Fe(CO)2(THF)BF4], It appears that the enol esters are formed by an unusual 1,2-aryl shift from a possible intermediate (13), which in turn is formed from the reaction of the iron aldehyde complex (12) with ethyl diazoacetate (see Scheme 4). 

Asymmetric hydroboration.1 The key step in a synthesis of natural (+ )-hir-sutic add-C (1), based on an earlier synthesis of racemic 1, is an efficient asymmetric hydroboration of the meso-alkene 2. Reaction of 2 with (+ )-diisopinocampheyl-borane (90% ee) followed by oxidation provides the exo-alcohol 3 in 73% yield and in 92% optical purity. Ring expansion of the corresponding ketone with ethyl diazoacetate is not regioselective even in the presence of BF3 etherate or (C2H5)30+ BF4, but does afford the desired a-keto ester in the presence of SbCl5 (8, 500-501). Decarboxylation of the crude product gives (— )-4 in 90% ee after chromatography. 

Enamine formation occurs by the thermolysis of diazo compounds (Scheme 150)67 109,278 284 288,304 332 453 454 via a carbene-like intermediate.284 332 When R1 = Ph, it enters into competition with hydrogen migration,284,332 and the electrophilic character of the carbene enhances the migration of the dimethylaminophenyl more than the phenyl.332 When triazoline synthesis is carried out at temperatures higher than that at which thermolysis of diazo compounds occurs, enamines are obtained exclusively, as in the addition of phenyl azide to cinnamic nitriles and ketones, with phenyl migration dominating in the nitrile.284 Enamine is also formed quantitatively in the reaction of ethyl diazoacetate with benzylideneaniline at 110°C.455... 

Related to simple chain extension is ring expansion and contraction useful because some ring sizes are easier to make than others. So available cyclohexanone can be expanded into cycloheptanones such as the useful keto-ester 20 with an activated position for enolate reactions. The reagent is ethyl diazoacetate 18 readily available from glycine esters. Addition to the ketone 18 automatically... 

Aldehydes are efficiently converted to /3-diketo esters in 50-90 % yield by addition of ethyl diazoacetate in the presence of SnCl2 (Eq. 5). Although the reaction can be effected by a variety of Lewis acids, SnCl2, BF3, and GeCl2 are the most effective [14]. 1,3-Diketones can be prepared in 42-90 % yield by SnCl2-catalyzed reaction of a-diazo ketones with aldehydes (Eq. 6) [15]. 

The synthesis and relative stability of 3,5-diacyl-4,5-dihydro-l//-pyrazoles prepared by dipolar cycloaddition of enones and a-diazoketones has been published <2004JOC9085>. 3-Acyl-4-aryl-2-pyrazolines have been synthesized by the reaction of a,/3-unsaturated ketones with diazomethane <1996IJB1091>. Ethyl diazoacetate added to 1,3-diarylpropenones in a regioselective fashion to give the intermediate 4,5-dihydto-3//-pyrazole derivative 1,3-hydride shift in the latter led to the formation of the isomeric ethyl 4-aryl-5-aroyl-4,5-dihydro-l//-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-l/7-pyrazole-5-carboxylate in a ratio of 5 1 <2001RJ01517>. 1,3-Dipolar cycloaddition of 2-diazopropane with diarylideneacetones afforded diastereomeric bis-A -pyrazolines <1999T449>. 

Aryl diazomethanes and ethyl diazoacetate lose nitrogen completely when hydrogenated over palladium in neutral medium at room temperature and atmospheric pressure. Aryl diazoketones, however, under the same conditions, give the a-amino ketones which condense directly to the dihydropyrazines. The addition of acetic acid to the solvent for this later reaction permits the isolation of the amino ketone (Eqn. 19.32). With dilute hydrochlorie acid in the reaction mixture, complete loss of the nitrogen was observed. The hydrogenation of alkyl diazoketones in neutral or acetic acid solution results in hydrazone formation (Eqn. 19.33). ... 

In a mechanistic study on the Lewis acid catalyzed addition of ethyl diazoacetate to ketones a similar profile of rearrangement to the 3-keto esters was observed (Scheme 9). In the same reaction with acetophenones, substitution on the benzene ring was found to only slightly affect the otherwise 90 10 preference for migration of aryl versus methyl. ... 

The one-carbon expansion of cyclohexanones with introduction of a carbonyl group, trifluromethyl, cyano, phosphonate or benzenesulfonate has also been reported to proceed in the presence of Lewis acids (Scheme 14). The analogous reactions of larger ring ketones [expressed as ring size (yield)] with ethyl diazoacetate [7 (81%), 8 (85%)] and phenylsulfonyldiazomethane [7 (86%), 8 (27%), 12 (43%), 14 (48%), 15 (54%) and 16 (58%)] have also been reported. In the reaction of ethyl diazoacetate and... 

Three-membered heterocycles. Decomposition of diazo compounds by the iron complex in the presence of imines leads to aziridines. An analogous reaction of diazoalkanes with aldehydes gives some epoxides and the rearrangement products (ketones) owing to the Lewis acidic nature of the catalyst. Ethyl diazoacetate behaves differently, as 1,2-aryl shift occurs during the reaction. ... 

Spencer et at. used this reaction as a key step in the synthesis of racemic methyl vinhaticoate (6), a tetracyclic furanoid diterpene. Thus treatment of the a-methoxy-methylene ketone (4) with ethyl diazoacetate in the presence of copper sulfate... 

Schonberg and Frese987 report that reaction of ethyl diazoacetate or a diazo ketone with an aromatic thioketone in the presence of copper powder gives the / ,/ -disubstituted acrylic ester or the, / -unsaturated ketone, respectively, in 80-90% yield. 

Z)-Enediones. a-Diazo ketones dimerize with decomposition on exposure to the Ru-complex. As more than statistical quantitites of cross-reaction products are obtained from an a-diazo ketone with either ethyl diazoacetate or trimethylsilyldiazomethane, the method has a preparative value for the corresponding unsymmetrical (Z)-enones. 

Ethyl tetrahydrofuran-2-carboxylates. p-Alkoxy carbonyl compounds in which the alkoxy group is readily detached in the presence of a Lewis acid undergo condensation with ethyl diazoacetate. Tin(IV) chloride is a suitable catalyst for P-alkoxy aldehydes, but it requires zirconium(IV) chloride to effect a reaction with P-alkoxy ketones. 

The action of phosgene or thionyl chloride on the )V-(benzyl-oxycarbonyl)amino-acids PhCH202CNHCHRC02H (R == PhCH2 or Pr ) yields 2-oxazolin-5-ones (522), contrary to a previous report/ Numerous 3-oxazolin-5-ones (523 R , R R = alkyl or Ph) have been prepared from hydroxylamino-acids H0NHCHR C02H and ketones R COR. The revised structure (524) has been established by X-ray diffraction for the product of the reaction of ethyl diazoacetate with di-isopropylcarbodi-imide, catalysed by salts of transition metals. Treatment of the diazomethylphosphoryl compound (Me0)2P(0)CHN2 with aroyl isocyanates affords the 2-oxazolin-4-ones (525)/ ... 

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