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Synthesis of Indoles by Reductive Cyclization of Nitro Compounds Using Formate Esters as CO Surrogates
Author(s) -
Ahmed Fouad Manar,
Ferretti Francesco,
Formenti Dario,
Milani Fabio,
Ragaini Fabio
Publication year - 2021
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.202100789
Subject(s) - chemistry , formate , decarbonylation , catalysis , aryl , nitro , methyl formate , alkyl , ruthenium , medicinal chemistry , palladium , reductive elimination , combinatorial chemistry , organic chemistry , alcohol
Alkyl and aryl formate esters were evaluated as CO sources in the Pd‐ and Pd/Ru‐catalyzed reductive cyclization of 2‐nitrostyrenes to give indoles. Whereas the use of alkyl formates requires the presence of a ruthenium catalyst such as Ru 3 (CO) 12 , the reaction with phenyl formate can be performed by using a Pd/phenanthroline complex alone. Phenyl formate was found to be the most effective CO source and the desired products were obtained in excellent yields, often higher than those previously reported using pressurized CO. The reaction tolerates many functional groups, including sensitive ones like a free aldehydic group or a pendant pyrrole. Detailed experiments and kinetic studies allow to conclude that the activation of phenyl formate is base‐catalyzed and that the metal doesn't play a role in the decarbonylation step. The reactions can be performed in a single thick‐walled glass tube with as little as 0.2 mol‐% palladium catalyst and even on a 2 g scale. The same protocol can be extended to other nitro compounds, affording different heterocycles.