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Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor

Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increas...

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Autores principales: Ibrahim, Malek Y. S., Abolhasani, Milad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068773/
https://www.ncbi.nlm.nih.gov/pubmed/35508490
http://dx.doi.org/10.1038/s41467-022-30175-0
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author Ibrahim, Malek Y. S.
Abolhasani, Milad
author_facet Ibrahim, Malek Y. S.
Abolhasani, Milad
author_sort Ibrahim, Malek Y. S.
collection PubMed
description Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H–H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity.
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spelling pubmed-90687732022-05-05 Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor Ibrahim, Malek Y. S. Abolhasani, Milad Nat Commun Article Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H–H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity. Nature Publishing Group UK 2022-05-04 /pmc/articles/PMC9068773/ /pubmed/35508490 http://dx.doi.org/10.1038/s41467-022-30175-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ibrahim, Malek Y. S.
Abolhasani, Milad
Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title_full Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title_fullStr Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title_full_unstemmed Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title_short Recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
title_sort recyclable cooperative catalyst for accelerated hydroaminomethylation of hindered amines in a continuous segmented flow reactor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068773/
https://www.ncbi.nlm.nih.gov/pubmed/35508490
http://dx.doi.org/10.1038/s41467-022-30175-0
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