Acetic acid, diazoesters

Unexpectedly, some diazoesters seem to react by way of carbene intermediates even in highly ionic media at room temperature.276 With acetic acid alone 2-furyldiazoacetic ester supplies two products retaining the furan ring. But if the acetic acid is mixed with ether or dichloromethane then a Z-alkenyne (Scheme 53) appears just as if a carbene had been formed. The... 

The -ketoester (90) (R = Bu ) undergoes hydrolysis and decarboxylation on treatment with acid and subsequent heating, yielding the 5-acetonyl derivative (89). In contrast, when (90) (R = Et) is allowed to react with aqueous acid, the acetic acid (91) (R = H) is isolated (Scheme 22) <82M793>. Treatment of the methyl ester (91) (R = R = Me) with triethylamine and tosyl azide leads to the diazoester which was shown by IR and NMR spectroscopy to exist in the open chain form (93) and not the cyclic form (92) (Scheme 22) <92JHC713>. 

Thallium(m) acetate effects a one-step synthesis of aliphatic a-acyloxy-carboxylic acids (Scheme 28) the transition state (92) is proposed. a-Aminoesters are readily oxidized to the corresponding a-diazoesters by isoamyl nitrite in the presence of acetic acid. A review has been published on the radical addition of carboxylic acids and derivatives to unsaturated linkages. ... 

Although the present procedure illustrates the formation of the diazoacetic ester without isolation of the intermediate ester of glyoxylic acid />-toluenesulfonylhydrazone, the two geometric isomers of this hydrazone can be isolated if only one molar equivalent of triethylamine is used in the reaction of the acid chloride with the alcohol. The extremely mild conditions required for the further conversion of these hydrazones to the diazo esters should be noted. Other methods for decomposing arylsulfonyl-hydrazones to form diazocarbonyl compounds have included aqueous sodium hydroxide, sodium hydride in dimethoxyethane at 60°, and aluminum oxide in methylene chloride or ethyl acetate." Although the latter method competes in mildness and convenience with the procedure described here, it was found not to be applicable to the preparation of aliphatic diazoesters such as ethyl 2-diazopropionate. Hence the conditions used in the present procedure may offer a useful complement to the last-mentioned method when the appropriate arylsulfonylhydrazone is available. 

Lewis acids efficiently catalyze the transfer of diazoketones and diazoesters to amides and nitriles to furnish 2,4,5-trisubstimted oxazoles (Scheme 1.49). In particular, Eguchi and co-workers found that BF3 OEt2 was the best catalyst for reaction of the adamantyl diazoketoester 180 with acetonitrile. Attempts to prepare 181 using Rh(II)acetate or photolysis were unsuccessful. Similarly, Ibata and Isogami °° described a general synthesis of 5-aryl-2-(chloromethyl)oxazoles 183 from a BF3.0Et2-catalyzed addition of a-diazoacetophenones 182 with chloro-acetonitrile. The yields were quite respectable (Table 1.12). 

On the way to further extension of the scope of Cp Co "-catalyzed C-H functionalization, Glorius and coworkers developed a condensation reaction of 2-arylpyridine derivatives and diazoesters to form unique polycyclic heteroaromatics having 6//-pyrido[2,l-a]isoquinolin-6-one skeletons (Scheme 10.15) [38]. The reaction is achieved by the combination of a bench-stable Co precatalyst [Cp Co(CO)l2] [39], a silver salt (AgSbFg), and an acetate source (KOAc) in trifluoroethanol. The in situ-formed Cp Co catalyst is proposed to play a dual role in this condensation reaction. First, it promotes formal carbene insertion into the ortho C-H bond through pyridine-directed C-H metalation, cobalt-carbene formation, carbene insertion into the aryl-Co bond, and protodemetalation. Second, it acts as a Lewis acid to facilitate nucleophilic attack of the pyridine moiety to the ester group, which eventually leads to the product through aromatization and elimination of methanol. The thus-synthesized polycyclic heteroarenes exhibit bright and color-tunable fluorescence in solution and in the solid state. 

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