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Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines
A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig re...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261767/ https://www.ncbi.nlm.nih.gov/pubmed/34276927 http://dx.doi.org/10.1039/d1sc01217g |
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author | Rani, Soniya Dash, Soumya Ranjan Bera, Asish Alam, Md Nirshad Vanka, Kumar Maity, Pradip |
author_facet | Rani, Soniya Dash, Soumya Ranjan Bera, Asish Alam, Md Nirshad Vanka, Kumar Maity, Pradip |
author_sort | Rani, Soniya |
collection | PubMed |
description | A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts. |
format | Online Article Text |
id | pubmed-8261767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-82617672021-07-16 Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines Rani, Soniya Dash, Soumya Ranjan Bera, Asish Alam, Md Nirshad Vanka, Kumar Maity, Pradip Chem Sci Chemistry A phosphite mediated stereoretentive C–H alkylation of N-alkylpyridinium salts derived from chiral primary amines was achieved. The reaction proceeds through the activation of the N-alkylpyridinium salt substrate with a nucleophilic phosphite catalyst, followed by a base mediated [1,2] aza-Wittig rearrangement and subsequent catalyst dissociation for an overall N to C-2 alkyl migration. The scope and degree of stereoretention were studied, and both experimental and theoretical investigations were performed to support an unprecedented aza-Wittig rearrangement–rearomatization sequence. A catalytic enantioselective version starting with racemic starting material and chiral phosphite catalyst was also established following our understanding of the stereoretentive process. This method provides efficient access to tertiary and quaternary stereogenic centers in pyridine systems, which are prevalent in drugs, bioactive natural products, chiral ligands, and catalysts. The Royal Society of Chemistry 2021-05-28 /pmc/articles/PMC8261767/ /pubmed/34276927 http://dx.doi.org/10.1039/d1sc01217g Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/ |
spellingShingle | Chemistry Rani, Soniya Dash, Soumya Ranjan Bera, Asish Alam, Md Nirshad Vanka, Kumar Maity, Pradip Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title | Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title_full | Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title_fullStr | Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title_full_unstemmed | Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title_short | Phosphite mediated asymmetric N to C migration for the synthesis of chiral heterocycles from primary amines |
title_sort | phosphite mediated asymmetric n to c migration for the synthesis of chiral heterocycles from primary amines |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261767/ https://www.ncbi.nlm.nih.gov/pubmed/34276927 http://dx.doi.org/10.1039/d1sc01217g |
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