Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis
Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrol...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/12/3661 |
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| author | Ahmed Numan Matthew Brichacek |
| author_facet | Ahmed Numan Matthew Brichacek |
| author_sort | Ahmed Numan |
| collection | DOAJ |
| description | Organophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries. Herein, enantioenriched phosphorus centers have been synthesized using chiral nucleophilic catalysis. Racemic <i>H</i>-phosphinate species were coupled with nucleophilic alcohols under halogenating conditions. Chiral phosphonate products were synthesized in acceptable yields (33–95%) and modest enantioselectivity (up to 62% <i>ee</i>) was observed after identification of an appropriate chiral catalyst and optimization of the solvent, base, and temperature. Nucleophilic catalysis has a tremendous potential to produce enantioenriched phosphate mimics that could be used as prodrugs or chemical biology probes. |
| first_indexed | 2024-03-10T10:22:23Z |
| format | Article |
| id | doaj.art-55f552fc0f38447d8d4ecdbe419f8f8b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:22:23Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-55f552fc0f38447d8d4ecdbe419f8f8b2023-11-22T00:16:27ZengMDPI AGMolecules1420-30492021-06-012612366110.3390/molecules26123661Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic CatalysisAhmed Numan0Matthew Brichacek1Department of Chemistry, University of Maine, Orono, ME 04469, USADepartment of Chemistry, University of Maine, Orono, ME 04469, USAOrganophosphates have been widely used in agrochemistry, as reagents for organic synthesis, and in biochemistry. Phosphate mimics possessing four unique substituents, and thereby a chirality center, are useful in transition metal catalysis and as nucleotide therapeutics. The catalytic, stereocontrolled synthesis of phosphorus-stereogenic centers is challenging and traditionally depends on a resolution or use of stochiometric auxiliaries. Herein, enantioenriched phosphorus centers have been synthesized using chiral nucleophilic catalysis. Racemic <i>H</i>-phosphinate species were coupled with nucleophilic alcohols under halogenating conditions. Chiral phosphonate products were synthesized in acceptable yields (33–95%) and modest enantioselectivity (up to 62% <i>ee</i>) was observed after identification of an appropriate chiral catalyst and optimization of the solvent, base, and temperature. Nucleophilic catalysis has a tremendous potential to produce enantioenriched phosphate mimics that could be used as prodrugs or chemical biology probes.https://www.mdpi.com/1420-3049/26/12/3661asymmetric synthesisnucleophilic catalystphosphorylationstereogenic phosphorusdynamic kinetic resolution |
| spellingShingle | Ahmed Numan Matthew Brichacek Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis Molecules asymmetric synthesis nucleophilic catalyst phosphorylation stereogenic phosphorus dynamic kinetic resolution |
| title | Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis |
| title_full | Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis |
| title_fullStr | Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis |
| title_full_unstemmed | Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis |
| title_short | Asymmetric Synthesis of Stereogenic Phosphorus P(V) Centers Using Chiral Nucleophilic Catalysis |
| title_sort | asymmetric synthesis of stereogenic phosphorus p v centers using chiral nucleophilic catalysis |
| topic | asymmetric synthesis nucleophilic catalyst phosphorylation stereogenic phosphorus dynamic kinetic resolution |
| url | https://www.mdpi.com/1420-3049/26/12/3661 |
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