A general synthesis of indol-3-carboxylic esters by direct Pd-catalyzed oxidative carbonylation of readily available 2-alkynylaniline derivatives is reported. In particular, 2-alkynylanilines bearing an internal triple bond and a secondary amino group (1) were directly converted into indole-3-carboxylic esters 2 in fair to good yields (50-84%) when let to react with CO, O2, and an alcohol in the presence of the PdI2-KI catalytic system, under relatively mild conditions [100 °C and 20 atm (at 25 °C) of a 4:1 mixture CO-air]. On the other hand, under similar conditions, but in the presence of HC(OMe)3, 2-alkynylanilines bearing an internal triple bond and a primary amino group (7) afforded 1-(dimethoxymethyl)indole-3-carboxylic esters 9 through the intermediate formation of N-(dimethoxymethyl)-2-alkynylaniline derivatives II. Compounds 9 could be conveniently converted into N-unsubstituted indol-3-carboxylic esters 10 by a simple acidic treatment carried out in MeOH-H2O at 80 °C.

A General Synthesis of Indole-3-carboxylic Esters by Palladium-Catalyzed Direct Oxidative Carbonylation of 2-Alkynylaniline Derivatives

GABRIELE, Bartolo;VELTRI, Lucia;Mancuso R;
2012

Abstract

A general synthesis of indol-3-carboxylic esters by direct Pd-catalyzed oxidative carbonylation of readily available 2-alkynylaniline derivatives is reported. In particular, 2-alkynylanilines bearing an internal triple bond and a secondary amino group (1) were directly converted into indole-3-carboxylic esters 2 in fair to good yields (50-84%) when let to react with CO, O2, and an alcohol in the presence of the PdI2-KI catalytic system, under relatively mild conditions [100 °C and 20 atm (at 25 °C) of a 4:1 mixture CO-air]. On the other hand, under similar conditions, but in the presence of HC(OMe)3, 2-alkynylanilines bearing an internal triple bond and a primary amino group (7) afforded 1-(dimethoxymethyl)indole-3-carboxylic esters 9 through the intermediate formation of N-(dimethoxymethyl)-2-alkynylaniline derivatives II. Compounds 9 could be conveniently converted into N-unsubstituted indol-3-carboxylic esters 10 by a simple acidic treatment carried out in MeOH-H2O at 80 °C.
Synthetic methods; Nitrogen heterocycles; Alkynes; Carbonylation; Cyclization; Palladium; Indoles; Heterocycles
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/135974
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