The reductive cyclization reaction of o-nitrostyrenes to generate indoles has been investigated for three decades using CO as a cheap reducing agent, but it remains an interesting area of research and improvements. However, using toxic CO gas has several drawbacks. As a result, it is highly preferable to use safe and efficient surrogates for in situ generation of CO from nontoxic and affordable sources. Among several CO sources that have been previously explored for the generation of gaseous CO, here we report the use of cheap and readily available formic acid as an effective reductant for the reductive cyclization of o-nitrostyrenes. The reaction is air and water tolerant and provides the desired indoles in yields up to 99%, at a low catalyst loading (0.5 mol %) and without generating toxic or difficult to separate byproducts. A cheap glass thick-walled "pressure tube" can be used instead of less available autoclaves, even on a 2 g scale, thus widening the applicability of our protocol.

Formic Acid as Carbon Monoxide Source in the Palladium-Catalyzed N-Heterocyclization of o-Nitrostyrenes to Indoles / M.A. Fouad, F. Ferretti, F. Ragaini. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1520-6904. - 88:8(2023 Apr 21), pp. 5108-5117. [10.1021/acs.joc.2c02613]

Formic Acid as Carbon Monoxide Source in the Palladium-Catalyzed N-Heterocyclization of o-Nitrostyrenes to Indoles

M.A. Fouad
Primo
;
F. Ferretti
Penultimo
;
F. Ragaini
Ultimo
2023

Abstract

The reductive cyclization reaction of o-nitrostyrenes to generate indoles has been investigated for three decades using CO as a cheap reducing agent, but it remains an interesting area of research and improvements. However, using toxic CO gas has several drawbacks. As a result, it is highly preferable to use safe and efficient surrogates for in situ generation of CO from nontoxic and affordable sources. Among several CO sources that have been previously explored for the generation of gaseous CO, here we report the use of cheap and readily available formic acid as an effective reductant for the reductive cyclization of o-nitrostyrenes. The reaction is air and water tolerant and provides the desired indoles in yields up to 99%, at a low catalyst loading (0.5 mol %) and without generating toxic or difficult to separate byproducts. A cheap glass thick-walled "pressure tube" can be used instead of less available autoclaves, even on a 2 g scale, thus widening the applicability of our protocol.
Settore CHIM/03 - Chimica Generale e Inorganica
Settore CHEM-03/A - Chimica generale e inorganica
Settore CHEM-05/A - Chimica organica
   Piano di Sostegno alla Ricerca 2015-2017 - Linea 2 "Dotazione annuale per attività istituzionali" (anno 2021)
   UNIVERSITA' DEGLI STUDI DI MILANO
21-apr-2023
19-gen-2023
https://pubs.acs.org/doi/10.1021/acs.joc.2c02613
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/953013
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