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A General Synthesis of Indole‐3‐carboxylic Esters by Palladium‐Catalyzed Direct Oxidative Carbonylation of 2‐Alkynylaniline Derivatives
Author(s) -
Gabriele Bartolo,
Veltri Lucia,
Mancuso Raffaella,
Salerno Giuseppe,
Costa Mirco
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200120
Subject(s) - chemistry , carbonylation , indole test , catalysis , alcohol , medicinal chemistry , triple bond , palladium , oxidative phosphorylation , organic chemistry , double bond , carbon monoxide , biochemistry
A general synthesis of indole‐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, O 2 , and an alcohol in the presence of the PdI 2 /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 indole‐3‐carboxylic esters 10 by a simple acidic treatment carried out in MeOH/H 2 O at 80 °C.