Gold/scandium bimetallic relay catalysis of formal [5+2]- and [4+2]-annulations: access to tetracyclic indole scaffolds

Abstract

A series of benzo[b]carbazole and cyclohepta[b]indole derivatives were afforded in a 77% average yield with excellent regioselectivities enabled by Au(i)/Sc(iii) bimetallic relay catalysis.

Gold-based enantioselective bimetallic catalysis

“…Scheme 18c). 33 Notably, the authors attempted this formal [5+2]-annulation reaction in an asymmetric fashion by examining various chiral BOX ligands and Lewis acid catalysts. However, product 18h was obtained with maximum of 24% ee.…”

Sc(iii)-Based metal–organic frameworks

“…73 The incorporation of secondary metal ions in MOFs offers excellent prospects regarding desired applications, especially in gas capture and catalysis, as it provides better tailoring of structure and functionality. Recently, bimetallic combinations of gold-scandium 74 and silver-scandium 75 have been explored as novel catalytic systems for the production of high-value compounds with excellent regioselectivity/diastereoselectivity. These bimetallic systems could be incorporated in MOFs as well to explore new catalytic applications.…”

Synergistic Sc(III)/Au(I)-Catalyzed Dearomative Spiroannulation of 2-(Ethynyl)aryl Cyclopropanes with 2-Aryl Indoles

“…Based on the mechanistic studies and our previous report, a plausible mechanism for this spiroannulation is proposed in Scheme . First, the carbonyl group of 2-(ethynyl)­phenyl DAC 2aa coordinates the Sc­(III) catalyst to form intermediate A .…”

“…Recently, we disclosed a bimetallic-catalyzed tandem alkylation/migration of 2-(2alkynyl)aryl cyclopropanes (ACPs) with indoles to afford tetracyclic indoles. 16 We hypothesized that the spiroindolenines could be accessed by the Sc(III)/Au(I) bimetalliccatalyzed alkylation/5-exo-dig cyclization cascade of orthoterminal alkyne-substituted DACs with C2-substituted indoles when the migration process is intentionally interrupted. As part of our ongoing efforts to explore the diverse reactivity of ACPs, we herein report a dearomative spiroannulation of orthoterminal-alkyne-substituted DACs with C2-substituted indoles to diastereoselectively access spiroindolenines enabled by gold/scandium bimetallic catalysis (Scheme 1C).…”

“…Notably, the above elegant cases focused on the tandem cyclizations of terminal-alkyne-functionalized indoles. Recently, we disclosed a bimetallic-catalyzed tandem alkylation/migration of 2-(2-alkynyl)­aryl cyclopropanes (ACPs) with indoles to afford tetracyclic indoles . We hypothesized that the spiroindolenines could be accessed by the Sc­(III)/Au­(I) bimetallic-catalyzed alkylation/5- exo -dig cyclization cascade of ortho -terminal alkyne-substituted DACs with C2-substituted indoles when the migration process is intentionally interrupted.…”