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. 2023 Dec 14;15(4):1318-1323.
doi: 10.1039/d3sc06409c. eCollection 2024 Jan 24.

A four-component reaction to access 3,3-disubstituted indolines via the palladium-norbornene-catalyzed ortho amination/ ipso conjunctive coupling

Alexander J Rago  1 , Rong Ye  1 , Xin Liu  1 , Guangbin Dong  1
Affiliations

A four-component reaction to access 3,3-disubstituted indolines via the palladium-norbornene-catalyzed ortho amination/ ipso conjunctive coupling

Alexander J Rago et al. Chem Sci. .

Abstract

As an important class of multicomponent reactions, the palladium/norbornene (Pd/NBE) cooperative catalysis has been mainly restricted to the coupling of an aryl halide, an electrophile and a nucleophile. Here, we report the development of a Pd/NBE-catalyzed four-component reaction, which involves ortho C-H amination/ipso conjunctive coupling using an alkene and an external nucleophile. The use of alkene-tethered nitrogen electrophiles provides a rapid and modular synthesis of 3,3-disubstituted indolines from readily available aryl iodides. The reaction exhibits broad functional group tolerance, and its utility is exemplified in a streamlined formal synthesis of a rhodamine dye. Preliminary results of the asymmetric version of this reaction have also been obtained.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. The Pd/NBE cooperative catalysis.
Fig. 1
Fig. 1. Representative bioactive compounds bearing 3,3′-disubstituted indoline moieties.
Scheme 2
Scheme 2. Proposed catalytic cycle.
Scheme 3
Scheme 3. Synthetic application. aThe reaction was carried out with 6 (0.1 mmol), 2b (0.2 mmol), 3b (0.12 mmol), Pd(TFA)2 (15 mol%), L2 (35 mol%), N1 (100 mol%), Cs2CO3 (0.25 mmol) in 1.0 mL of toluene at 100 °C for 12 h.
See this image and copyright information in PMC

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