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Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles
An asymmetric allylic alkylation/Cope rearrangement (AAA/[3,3]) capable of stereoselectively constructing vicinal stereocenters has been developed. Strategically integrated 4-methylation on the 3,3-dicyano-1,5-diene controls stereoselectivity and drives Cope rearrangement equilibrium in the forward...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993902/ https://www.ncbi.nlm.nih.gov/pubmed/36908968 http://dx.doi.org/10.1039/d2sc07021a |
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author | Nilova, Aleksandra Mannchen, Michael D. Noel, Abdias N. Semenova, Evgeniya Grenning, Alexander J. |
author_facet | Nilova, Aleksandra Mannchen, Michael D. Noel, Abdias N. Semenova, Evgeniya Grenning, Alexander J. |
author_sort | Nilova, Aleksandra |
collection | PubMed |
description | An asymmetric allylic alkylation/Cope rearrangement (AAA/[3,3]) capable of stereoselectively constructing vicinal stereocenters has been developed. Strategically integrated 4-methylation on the 3,3-dicyano-1,5-diene controls stereoselectivity and drives Cope rearrangement equilibrium in the forward direction. The AAA/[3,3] sequence rapidly converts abundant achiral and racemic starting materials into valuable (hetero)cycloalkane building blocks bearing significant functional and stereochemical complexity, highlighting the value of (hetero)cyclohexylidenemalononitriles as launching points for complex heterocycle synthesis. On this line, the resulting alkylidenemalononitrile moiety can be readily converted into amides via Hayashi–Lear amidation to ultimately yield amido-piperidines, tropanes, and related scaffolds with 3–5 stereocenters and drug-like functionality. |
format | Online Article Text |
id | pubmed-9993902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-99939022023-03-09 Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles Nilova, Aleksandra Mannchen, Michael D. Noel, Abdias N. Semenova, Evgeniya Grenning, Alexander J. Chem Sci Chemistry An asymmetric allylic alkylation/Cope rearrangement (AAA/[3,3]) capable of stereoselectively constructing vicinal stereocenters has been developed. Strategically integrated 4-methylation on the 3,3-dicyano-1,5-diene controls stereoselectivity and drives Cope rearrangement equilibrium in the forward direction. The AAA/[3,3] sequence rapidly converts abundant achiral and racemic starting materials into valuable (hetero)cycloalkane building blocks bearing significant functional and stereochemical complexity, highlighting the value of (hetero)cyclohexylidenemalononitriles as launching points for complex heterocycle synthesis. On this line, the resulting alkylidenemalononitrile moiety can be readily converted into amides via Hayashi–Lear amidation to ultimately yield amido-piperidines, tropanes, and related scaffolds with 3–5 stereocenters and drug-like functionality. The Royal Society of Chemistry 2023-02-14 /pmc/articles/PMC9993902/ /pubmed/36908968 http://dx.doi.org/10.1039/d2sc07021a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Nilova, Aleksandra Mannchen, Michael D. Noel, Abdias N. Semenova, Evgeniya Grenning, Alexander J. Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title | Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title_full | Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title_fullStr | Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title_full_unstemmed | Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title_short | Vicinal stereocenters via asymmetric allylic alkylation and Cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
title_sort | vicinal stereocenters via asymmetric allylic alkylation and cope rearrangement: a straightforward route to functionally and stereochemically rich heterocycles |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9993902/ https://www.ncbi.nlm.nih.gov/pubmed/36908968 http://dx.doi.org/10.1039/d2sc07021a |
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