Lewis Acid Catalyzed Regioselective Hydroheteroarylation of Pentafulvenes

Abstract

A diverse approach toward the catalytic regioselective nucleophilic addition of nitrogen heterocycles to Lewis acid activated pentafulvenes has been established. The developed protocol introduces pentafulvenes as nonsymmetrical alkenes for the hydroheteroarylation reaction, providing alkylidenecyclopentenylation at the C-3 position of indoles and the C-2 position of pyrrole.

Recent Advances in the Chemistry of Pentafulvenes

“…A wide range of transition metals were used for this purpose. − Very recently, our group established an exceptional strategy toward the regioselective hydroheteroarylation of pentafulvenes with various indoles 292 and pyrrole in the presence of a Lewis acid (Scheme ). This protocol does not need dry solvents or inert atmospheres, and readily occurs at ambient temperature. This is the first report on the endo selective 1,2-addition of a nucleophile to fulvene catalyzed by a Lewis acid.…”

Lewis Acid Promoted Regioselective Double Hydro(hetero)arylation of 6,6′‐Dialkyl‐Substituted Pentafulvenes: A Facile Approach to Bisindole Derivatives

“…On the basis of this unusual reactivity, we presumed that a double hydro(hetero)arylation of pentafulvene might occur if the amount of indole was doubled. In the initial monitoring, the reaction afforded the double heteroarylation product ( 3bb , 12 %) along with the monosubstituted indole ( 4bb , 75 %, Scheme ) . Various spectroscopic analyses clearly indicated that the product formed was the cyclopentenylated bisindole.…”

“…of N ‐methylindole ( 2a ) with 2 mol‐% of Cu(OTf) 2 (OTf = triflate) in CH 3 CN at room temperature regioselectively afforded the alkylidenecyclopentenylated indole 4aa in 99 % yield (Scheme ). The reaction was found to be general for pentafulvenes derived from aromatic aldehydes or ketones and several substituted indoles …”

“…With alkyl‐substituted fulvene 1b as the substrate for the hydro(hetero)arylation, the reaction afforded multiple products with varying numbers of pentafulvene units. On the contrary, the reaction afforded a double alkylidenecyclopentenylated indole at the C‐2 and C‐3 position, 8a , if the amount of diphenylfulvene was doubled (Scheme , path b) …”

“…In recent years, much attention has been devoted to the development of transition‐metal/Lewis acid catalysis routes for the hydro(hetero)arylation of alkenes and dienes . We have established a regioselective Lewis acid catalyzed hydro(hetero)arylation of pentafulvenes . Herein, we would like to describe the Lewis acid catalyzed double hydro(hetero)arylation of 6,6′‐dialkyl‐substituted pentafulvenes to form bisindole derivatives.…”