New synthesis of methyl 5-aryl or heteroaryl pyrrole-2-carboxylates by a tandem Sonogashira coupling/5-endo-dig-cyclization from β-iododehydroamino acid methyl esters and terminal alkynes

Abstract: A new and versatile ‘Pd’/CuI catalyzed protocol was developed for the synthesis in good to high yields of substituted pyrroles from N-Boc-β-iododehydroamino acid methyl esters and several terminal alkynes. This one-pot, two-step procedure occurs by a Sonogashira coupling followed by a 5-endo-dig-cyclization, which involves the nitrogen atom of the dehydroamino acid. After several experiments using different Pd(0) and Pd(II) species it was possible to establish the more general reaction conditions, which are: the use of a Pd(II) catalyst, CuI and Cs2CO3 as base in dry DMF at 70°C. The best yields were obtained with arylacetylenes bearing electron-donating groups and with electron-rich heteroarylacetylenes. [Copyright &y& Elsevier]