Rhodium-catalyzed migrative annulation and olefination of 2-aroylpyrroles with diazoesters

A one-pot synthesis of pyrrolo[1,2-c][1,3]oxazin-1-ones has been developed using the Rh-2(OAc)(4)-catalyzed annulation reaction of 2-aroyl-substituted NH-pyrroles with diazoesters. The reaction, in addition to the annulation product, affords two by-products: pyrrolylpyruvate ester and alpha-(methoxycarbonyloxy)-beta-pyrrol-2-yl cinnamate ester, which are converted to the pyrroboxazinone derivative under DBU catalysis in a one-pot fashion. Dimethyl diazomalonate reacts with pyrroles containing an acceptor-substituted aroyl group predominantly in the olefination fashion to form the cinnamate derivative, which can be isolated in moderate yields. Olefination of 2-aroylpyrroles is the main reaction when using methyl 2-diazoacetoacetate, methyl 2-diazo-2-(dimethoxyphosphoryl)acetate, and methyl 2-diazo-2-tosylacetate. The diazoester is embedded into both the annulation and olefination products in an unusually rearranged form. The experimental and DFT studies revealed an unprecedented reaction mechanism involving four catalytic cycles, one of which involves catalysis by Rh-2(OAc)(4), two by the starting pyrrole, and one by the methyl-hemiacetal of the final pyrroboxazinone.

Automated summary

A one-pot synthesis of pyrrolo[1,2-c][1,3]oxazin-1-ones has been achieved through the Rh-2(OAc)(4)-catalyzed annulation reaction of 2-aroyl-substituted NH-pyrroles with diazoesters. The reaction involves the formation of three different products: the annulation product, pyrrolylpyruvate ester, and alpha-(methoxycarbonyloxy)-beta-pyrrol-2-yl cinnamate ester, which are subsequently converted to the pyrroboxazinone derivative in a one-pot process catalyzed by DBU. The reaction mechanism involves four catalytic cycles, including Rh-2(OAc)(4) catalysis and catalysis by the starting pyrrole and the methyl-hemiacetal of the final pyrroboxazinone.