Cargando…
A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis
[Image: see text] A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promo...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2014
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954459/ https://www.ncbi.nlm.nih.gov/pubmed/24467274 http://dx.doi.org/10.1021/ja4126565 |
_version_ | 1782307477411332096 |
---|---|
author | Gao, Fang Carr, James L. Hoveyda, Amir H. |
author_facet | Gao, Fang Carr, James L. Hoveyda, Amir H. |
author_sort | Gao, Fang |
collection | PubMed |
description | [Image: see text] A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 S(N)2′:S(N)2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E. |
format | Online Article Text |
id | pubmed-3954459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-39544592015-01-28 A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis Gao, Fang Carr, James L. Hoveyda, Amir H. J Am Chem Soc [Image: see text] A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0–5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl–(pinacolatoboron) [alkenyl–B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 S(N)2′:S(N)2, and 99:1 enantiomeric ratio (er). NHC–Cu-catalyzed EAS with alkenyl–B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E. American Chemical Society 2014-01-28 2014-02-05 /pmc/articles/PMC3954459/ /pubmed/24467274 http://dx.doi.org/10.1021/ja4126565 Text en Copyright © 2014 American Chemical Society |
spellingShingle | Gao, Fang Carr, James L. Hoveyda, Amir H. A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title | A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title_full | A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title_fullStr | A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title_full_unstemmed | A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title_short | A Broadly Applicable NHC–Cu-Catalyzed Approach for Efficient, Site-, and Enantioselective Coupling of Readily Accessible (Pinacolato)alkenylboron Compounds to Allylic Phosphates and Applications to Natural Product Synthesis |
title_sort | broadly applicable nhc–cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954459/ https://www.ncbi.nlm.nih.gov/pubmed/24467274 http://dx.doi.org/10.1021/ja4126565 |
work_keys_str_mv | AT gaofang abroadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis AT carrjamesl abroadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis AT hoveydaamirh abroadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis AT gaofang broadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis AT carrjamesl broadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis AT hoveydaamirh broadlyapplicablenhccucatalyzedapproachforefficientsiteandenantioselectivecouplingofreadilyaccessiblepinacolatoalkenylboroncompoundstoallylicphosphatesandapplicationstonaturalproductsynthesis |