Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant

[Image: see text] A novel approach is reported for the enantioselective flow synthesis of rolipram comprising a telescoped asymmetric conjugate addition–oxidative aldehyde esterification sequence followed by trichlorosilane-mediated nitro group reduction and concomitant lactamization. The telescoped...

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Autores principales: Nagy, Bence S., Llanes, Patricia, Pericas, Miquel A., Kappe, C. Oliver, Ötvös, Sándor B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822492/
https://www.ncbi.nlm.nih.gov/pubmed/35050638
http://dx.doi.org/10.1021/acs.orglett.1c04300
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author Nagy, Bence S.
Llanes, Patricia
Pericas, Miquel A.
Kappe, C. Oliver
Ötvös, Sándor B.
author_facet Nagy, Bence S.
Llanes, Patricia
Pericas, Miquel A.
Kappe, C. Oliver
Ötvös, Sándor B.
author_sort Nagy, Bence S.
collection PubMed
description [Image: see text] A novel approach is reported for the enantioselective flow synthesis of rolipram comprising a telescoped asymmetric conjugate addition–oxidative aldehyde esterification sequence followed by trichlorosilane-mediated nitro group reduction and concomitant lactamization. The telescoped process takes advantage of a polystyrene-supported chiral organocatalyst along with in situ-generated persulfuric acid as a robust and scalable oxidant for direct aldehyde esterification. This approach demonstrates significantly improved productivity compared with earlier methodologies while ensuring environmentally benign metal-free conditions.
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spelling pubmed-88224922022-02-08 Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant Nagy, Bence S. Llanes, Patricia Pericas, Miquel A. Kappe, C. Oliver Ötvös, Sándor B. Org Lett [Image: see text] A novel approach is reported for the enantioselective flow synthesis of rolipram comprising a telescoped asymmetric conjugate addition–oxidative aldehyde esterification sequence followed by trichlorosilane-mediated nitro group reduction and concomitant lactamization. The telescoped process takes advantage of a polystyrene-supported chiral organocatalyst along with in situ-generated persulfuric acid as a robust and scalable oxidant for direct aldehyde esterification. This approach demonstrates significantly improved productivity compared with earlier methodologies while ensuring environmentally benign metal-free conditions. American Chemical Society 2022-01-20 2022-02-04 /pmc/articles/PMC8822492/ /pubmed/35050638 http://dx.doi.org/10.1021/acs.orglett.1c04300 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Nagy, Bence S.
Llanes, Patricia
Pericas, Miquel A.
Kappe, C. Oliver
Ötvös, Sándor B.
Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title_full Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title_fullStr Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title_full_unstemmed Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title_short Enantioselective Flow Synthesis of Rolipram Enabled by a Telescoped Asymmetric Conjugate Addition–Oxidative Aldehyde Esterification Sequence Using in Situ-Generated Persulfuric Acid as Oxidant
title_sort enantioselective flow synthesis of rolipram enabled by a telescoped asymmetric conjugate addition–oxidative aldehyde esterification sequence using in situ-generated persulfuric acid as oxidant
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8822492/
https://www.ncbi.nlm.nih.gov/pubmed/35050638
http://dx.doi.org/10.1021/acs.orglett.1c04300
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