InCl₃‐Mediated Addition of Indole to Isatogens: An Expeditious Synthesis of 13‐deoxy‐Isatisine A

Abstract

A strategy directed towards the total synthesis of isatisine A that involves several late-stage metal-catalyzed transformations that address the key carbon-carbon and carbon-heteroatom bond formations has been developed. As a part of this strategy, methods for the addition of indoles to isatogens that lead selectively to either 2,2-disubstituted N-hydroxyindolin-3-one or 2,2-disubstituted indolin-3-one compounds have been developed by employing InCl(3) as a catalyst or as the reagent. The present methods provide the first examples of the additions of indoles to the isatogen nucleus. To demonstrate its viability, the synthesis of 13-deoxy-isatisine A has been completed in ten steps from a known and easily available lactone.

Organocatalytic Enantioselective Mannich Reaction: Direct Access to Chiral β-Amino Esters

“…6 Consequently, a few methods have been reported for the enantioselective conversion of 3-indolinone-2-carboxylates into chiral compounds. 7 However, the construction of a chiral quaternary stereocenter is a challenging task for a synthetic chemist. 8 Furthermore, an asymmetric Mannich reaction is a powerful strategy to produce chiral ß-amino ketones and ß-amino esters.…”

“…On the other hand, a chiral 2,2-disubstituted indolin-3-one skeleton is often present in several biologically active natural products such as (+)-isatisine A, trigonoliimine C, mersicarpine, etc. , They are known to exhibit potent antiviral properties . Consequently, a few methods have been reported for the enantioselective conversion of 3-indolinone-2-carboxylates into chiral compounds . However, the construction of a chiral quaternary stereocenter is a challenging task for a synthetic chemist .…”

Pd‐Catalyzed One‐Pot Two‐Step Synthesis of 2‐(1H‐indol‐3‐yl)‐2‐phenylindolin‐3‐ones from 2‐Alkynyl Arylazides and Indoles

“…Based on its potential bioactivities, the synthesis of the indolin‐3‐ones with indoxyl functional group has been paid more attention. Many synthetic methods have been reported, such as trapping metallocarbene by organoazide, gold/copper co‐catalyzed oxidation of 2‐alkynylanilines, TEMPO/Pd‐catalyzed oxidation of indoles, DDQ‐promoted oxidative aza ‐Friedel‐Crafts alkylation of indole with 3‐indolelinone‐2‐carboxylates, InCl 3 ‐mediated addition of indol‐3‐one‐ N ‐oxide, Pd‐catalyzed oxidative dearomatization of 2‐arylindoles, visible light photocatalytic oxygenation of indoles and Mannich reaction of cyclic‐acylimines –. Although these reported reactions are efficient methods, the novel strategy for the preparation of indolin‐3‐ones bearing indoxyl group is still needed.…”

A modular total synthesis of (±)-trigonoliimine C

“…We employed an InCl 3mediated addition of indole C3 to an isatogen intermediate for the construction of the bis-indole core of isatisine A. [6][7][8] However, in the present case, the C2 of a tryptamine derivative needs to be added to the isatogen. This is one of the key reactions in our strategy that needs a detailed investigation.…”

“…[10][11][12] InCl 3 was found to be completely ineffective in carrying out the requisite transformation. 7 On the other hand, with the metal triflates employed such as zinc-, and ytterbium triflates, 9g intractable complex reaction mixtures were formed. The reaction with the [Au]-complex was facile at room temperature in dichloromethane and provided the corresponding indoleaddition product 8a with an intact N-OH unit.…”