2,3-Disubstituted Indoles by Stille Cross- Coupling Reaction

Significance

A one-pot procedure for the synthesis of 2-alkyl-3-substituted indoles from N-acyl-2-iodoanilines with 1-(tributylstannyl)-allenes is described. The initial Pd(0)-catalyzed Stille reaction leads to an allenyl intermediate, which, without isolation, is subjected to mild, TBAF-mediated cyclization to afford the 2-alkyl-3-substituted indoles in moderate to good yields. In addition, the effects of additives (e.g., TBAC, LiBr, LiCl) and phosphine ligands as well as electronic effects of the substituents in the iodoanilines were examined to establish optimized conditions. The procedure was also applied to the synthesis of indomethacin, a nonsteroidal anti-inflammatory drug.