Three-step solution-phase combinatorial access to 1,2-disubstituted and 1,2,5-trisubstituted pyrroles from carboxylic esters.
An efficient diversity-oriented strategy has been developed for the solution-phase parallel synthesis of di- and trisubstituted pyrrole libraries. Methyl esters 1 were effectively converted to 1,2-di- and 1,2,5-trisubstituted pyrroles 5 and 6 in three steps. Treatment of ester 1 with vinylmagnesium bromide in the presence of copper (I) cyanide yielded the corresponding homoallylic ketone 2, which was subjected to ozonolysis or Tsuji-Wacker oxidation to yield the respective cyclization precursors 3 and 4 after aqueous workup. Compounds 3 and 4 were condensed without further purification with a primary amine to afford the desired 1,2-di- or 1,2,5-trisubstituted pyrroles 5 and 6 in good yield and purity.
Hansford
Karl A
KA
Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre Ville, Montréal, Québec, H3C 3J7, Canada.
Zanzarova
Valeria
V
Dörr
Aurélie
A
Lubell
William D
WD