Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides
The isothiourea-catalyzed enantioselective 1,6-conjugate addition of <i>para</i>-nitrophenyl esters to 2,6-disubstituted <i>para</i>-quinone methides is reported. <i>para</i>-Nitrophenoxide, generated in situ from initial <i>N</i>-acylation of the isot...
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| Format: | Article |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6333 |
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| author | Jude N. Arokianathar Will C. Hartley Calum McLaughlin Mark D. Greenhalgh Darren Stead Sean Ng Alexandra M. Z. Slawin Andrew D. Smith |
| author_facet | Jude N. Arokianathar Will C. Hartley Calum McLaughlin Mark D. Greenhalgh Darren Stead Sean Ng Alexandra M. Z. Slawin Andrew D. Smith |
| author_sort | Jude N. Arokianathar |
| collection | DOAJ |
| description | The isothiourea-catalyzed enantioselective 1,6-conjugate addition of <i>para</i>-nitrophenyl esters to 2,6-disubstituted <i>para</i>-quinone methides is reported. <i>para</i>-Nitrophenoxide, generated in situ from initial <i>N</i>-acylation of the isothiourea by the <i>para</i>-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of <i>para</i>-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er). |
| first_indexed | 2024-03-10T05:56:38Z |
| format | Article |
| id | doaj.art-355f0306f6ad4c5f949bcd0c0470370b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:56:38Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-355f0306f6ad4c5f949bcd0c0470370b2023-11-22T21:19:41ZengMDPI AGMolecules1420-30492021-10-012621633310.3390/molecules26216333Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone MethidesJude N. Arokianathar0Will C. Hartley1Calum McLaughlin2Mark D. Greenhalgh3Darren Stead4Sean Ng5Alexandra M. Z. Slawin6Andrew D. Smith7EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKAstraZeneca, Oncology R&D, Research & Early Development, Darwin Building, 310, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, UKSyngenta, Jealott’s Hill International Research Centre, Bracknell RG42 6EY, UKEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKEaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UKThe isothiourea-catalyzed enantioselective 1,6-conjugate addition of <i>para</i>-nitrophenyl esters to 2,6-disubstituted <i>para</i>-quinone methides is reported. <i>para</i>-Nitrophenoxide, generated in situ from initial <i>N</i>-acylation of the isothiourea by the <i>para</i>-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of <i>para</i>-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).https://www.mdpi.com/1420-3049/26/21/6333isothioureaammonium enolatearyloxidequinone methideester functionalization1,6-conjugate addition |
| spellingShingle | Jude N. Arokianathar Will C. Hartley Calum McLaughlin Mark D. Greenhalgh Darren Stead Sean Ng Alexandra M. Z. Slawin Andrew D. Smith Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides Molecules isothiourea ammonium enolate aryloxide quinone methide ester functionalization 1,6-conjugate addition |
| title | Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides |
| title_full | Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides |
| title_fullStr | Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides |
| title_full_unstemmed | Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides |
| title_short | Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to <i>para</i>-Quinone Methides |
| title_sort | isothiourea catalyzed enantioselective α alkylation of esters via 1 6 conjugate addition to i para i quinone methides |
| topic | isothiourea ammonium enolate aryloxide quinone methide ester functionalization 1,6-conjugate addition |
| url | https://www.mdpi.com/1420-3049/26/21/6333 |
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