Indium-Catalyzed Regioselective β-Alkylation of Pyrroles with Carbonyl Compounds and Hydrosilanes and Its Application to Construction of a Quaternary Carbon Center with a β-Pyrrolyl Group.
Treatment of N-substituted pyrroles with carbonyl compounds and nucleophiles under indium catalysis was found to be a promising method for preparing β-alkylpyrroles without contamination by α-alkylpyrroles. With this methodology, a variety of alkyl groups, which are primary, secondary, and tertiary as well as cyclic and functionalized types, can be introduced in place onto the pyrrole ring. The simplicity performable as a catalytic one-step process is one of the important features of this reaction. The substituent on the nitrogen atom of the product β-alkylpyrrole can be removed easily by literature procedures. Therefore, the indium-catalyzed β-alkylation plus the N-deprotection is a powerful system for all six variations, which are N-substituted and N-unsubstituted β-alkylpyrroles having primary, secondary, and tertiary alkyl groups. Our method is applicable to synthesizing, albeit in two steps, β-pyrrolyl-group-connected unsymmetrical tetraarylmethanes that have not been addressed thus far. Mechanistic studies showed the following three aspects: (1) dipyrrolylalkanes produced in situ from the pyrrole and carbonyl compound are key intermediates, (2) the selective β-alkylation is attributed to the selective elimination of an α-pyrrolyl group from the dipyrrolylalkane intermediates, and (3) the indium Lewis acid catalyst is indispensable for the progress of both stages.
Department of Applied Chemistry, School of Science and Technology, Meiji University , 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Japan.
Shota
S
Nomiyama
Department of Applied Chemistry, School of Science and Technology, Meiji University , 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Japan.
Takahiro
T
Ogura
Department of Applied Chemistry, School of Science and Technology, Meiji University , 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Japan.
Hiroaki
0000-0003-0493-7733
H
Ishida
Department of Applied Chemistry, School of Science and Technology, Meiji University , 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Japan.
Kazuki
K
Aoki
Department of Applied Chemistry, School of Science and Technology, Meiji University , 1-1-1 Higashimita, Tama-ku, Kawasaki 214-8571, Japan.
Teruhisa
T
Tsuchimoto