Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A.
The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and pro...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826277504758841344 |
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| author | Wang, C Yu, M Kyle, A Jakubec, P Dixon, D Schrock, R Hoveyda, A |
| author_facet | Wang, C Yu, M Kyle, A Jakubec, P Dixon, D Schrock, R Hoveyda, A |
| author_sort | Wang, C |
| collection | OXFORD |
| description | The first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z), and nakadomarin A (15-membered ring: up to 97% Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule. |
| first_indexed | 2024-03-06T23:29:54Z |
| format | Journal article |
| id | oxford-uuid:6bab8a94-771a-4ec4-9626-01992262584c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:29:54Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:6bab8a94-771a-4ec4-9626-01992262584c2022-03-26T19:05:38ZEfficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6bab8a94-771a-4ec4-9626-01992262584cEnglishSymplectic Elements at Oxford2013Wang, CYu, MKyle, AJakubec, PDixon, DSchrock, RHoveyda, AThe first broadly applicable set of protocols for efficient Z-selective formation of macrocyclic disubstituted alkenes through catalytic ring-closing metathesis (RCM) is described. Cyclizations are performed with 1.2-7.5 mol% of a Mo- or W-based monoaryloxide pyrrolide (MAP) complex at 22 °C and proceed to complete conversion typically within two hours. Utility is demonstrated by synthesis of representative macrocyclic alkenes, such as natural products yuzu lactone (13-membered ring: 73% Z) epilachnene (15-membered ring: 91% Z), ambrettolide (17-membered ring: 91% Z), an advanced precursor to epothilones C and A (16-membered ring: up to 97% Z), and nakadomarin A (15-membered ring: up to 97% Z). We show that catalytic Z-selective cyclizations can be performed efficiently on gram-scale with complex molecule starting materials and catalysts that can be handled in air. We elucidate several critical principles of the catalytic protocol: 1) The complementary nature of the Mo catalysts, which deliver high activity but can be more prone towards engendering post-RCM stereoisomerization, versus W variants, which furnish lower activity but are less inclined to cause loss of kinetic Z selectivity. 2) Reaction time is critical to retaining kinetic Z selectivity not only with MAP species but with the widely used Mo bis(hexafluoro-tert-butoxide) complex as well. 3) Polycyclic structures can be accessed without significant isomerization at the existing Z alkenes within the molecule. |
| spellingShingle | Wang, C Yu, M Kyle, A Jakubec, P Dixon, D Schrock, R Hoveyda, A Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title | Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title_full | Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title_fullStr | Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title_full_unstemmed | Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title_short | Efficient and selective formation of macrocyclic disubstituted Z alkenes by ring-closing metathesis (RCM) reactions catalyzed by Mo- or W-based monoaryloxide pyrrolide (MAP) complexes: applications to total syntheses of epilachnene, yuzu lactone, ambrettolide, epothilone C, and nakadomarin A. |
| title_sort | efficient and selective formation of macrocyclic disubstituted z alkenes by ring closing metathesis rcm reactions catalyzed by mo or w based monoaryloxide pyrrolide map complexes applications to total syntheses of epilachnene yuzu lactone ambrettolide epothilone c and nakadomarin a |
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