Nitriles dimethyl diazomalonate

Much of the early work into the rhodium(II)-catalysed formation of oxazoles from diazocarbonyl compounds was pioneered by the group of Helquist. They first reported, in 1986, the rhodium(II) acetate catalysed reaction of dimethyl diazomalonate with nitriles.<86TL5559, 93T5445, 960S(74)229> A range of nitriles was screened, including aromatic, alkyl and vinyl derivatives with unsaturated nitriles, cyclopropanation was found to be a competing reaction (Table 3). 

Dimethyl diazomalonate undergoes reaction with nitriles in the presence of rhodium(II) acetate to give 2-substituted-4-carbomethoxy-l,3-oxazoles (255). The reaction proceeds with a wide range of nitriles,133-139 although cyclopropanation is a competing process in the case of unsaturated nitriles.129... 

A Rh2(OAc)4-catalyzed cycloaddition between nitrile 202 and dimethyl diazomalonate 203 gave oxazole 204 which was further elaborated into the side-chain of marine macrolide leucascandrolide A (Scheme 59) <2002JA13670>. 

In a model study, Helquist and co-workers described the reaction of dimethyl diazomalonate 128 with benzonitrile to prepare 5-methoxy-2-phenyl-4-oxazolecar-boxylic acid methyl ester 129 nearly quantitatively (Scheme 1.35). Several other 2-aryl-5-methoxy-4-oxazolecarboxylic acid methyl esters were prepared analogously. In addition, 2-aIkyl(aIkenyl)-5-methoxy-4-oxazolecarboxylic acid methyl esters were also prepared, although the yields for aliphatic nitriles were not as good, unless the nitrile was used as solvent. Other metal salts—including Rh2 (NHAc)4, Cu(OTf)2, Cu(C2Hs-acac)2, Rh2(02CC3H7)4, and Rh3(CO)ie— were not as effective as Rh2(OAc)4 in this reaction. 

Although Rh -catalyzed reaction of dimethyl diazomalonate with nitriles to afford 1,3-oxazoles (eq 4) generally gives high yields, it is incompatible with an a-amino function. Thus, an alternative route was proposed for preparation of oxazole derivatives of a-amino acids. This method involves Rh -catalyzed insertion into N-H bond of an amide, derived from the amino acid, followed by intramolecular condensation (eq 36). ... 

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