Oxazoles 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... 

The particular reaction described in Scheme 2 using dimethyl diazomalonate produces oxazoles 5 that bear a methoxy group at C-5. If desired, this substituent may be removed in some cases by reductive cleavage using LiB(Et)3H to give the 5-unsubstituted oxazoles 6.3.15 Alternatively, the 5-unsubstituted derivatives 6 may be obtained directly through the use of diazo formylacetate (2) in place of dimethyl diazomalonate (1).3 15 Some additional, representative examples of the use of 1 and 2 are shown below in the Table. 

ADDITIONAL EXAMPLES OF OXAZOLE FORMATION USING DIMETHYL DIAZOMALONATE 1 AND DIAZO FORMYLACETATE 2a... 

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>. 

One of the key steps in the total synthesis of phorboxazole A and B is the Rh(II)-catalyzed cycloaddition reaction of diethyl cyanomethylphosphonate with dimethyl diazomalonate to form the desired phosphonylated oxazole. ... 

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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