Regioselectivity Control in Alkylation Reactions of Indolyl Ambident Anion.

The regioselectivity of N- and C-3(β)-alkylations of indolylmetal salts was studied under various conditions. The effect of counter metal ion is crucial in determining the regioselectivity. In tetrahydrofuran, exclusive N-alkylation occurred with the potassium salt, but the extent of C-3-alkylation increased with the sodium and lithium salts and became predominant with the magnesium bromide salt. However, N-alkylation was favoured generally in more polar solvents and for alkyl toluene-P-sulphonates it was favoured even with magnesium bromide salts. The reactivity and regioselectivity of the alkylations were correlated with the calculated electron density of the indolyl anion and with 13C n.m.r. chemical shifts of the metal salts.