Modular sulfondiimine synthesis using a stable sulfinylamine reagent
Sulfondiimines—the double aza-analogues of sulfones—hold significant potential as leads in discovery chemistry, yet their application in this arena has been held back by the scarcity of appropriate synthetic routes. Existing methods employ sulfides as substrates, and rely on consecutive imination re...
| Main Authors: | , , |
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| Format: | Journal article |
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American Chemical Society
2019
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| _version_ | 1826291012997218304 |
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| author | Zhang, Z Davies, T Willis, M |
| author_facet | Zhang, Z Davies, T Willis, M |
| author_sort | Zhang, Z |
| collection | OXFORD |
| description | Sulfondiimines—the double aza-analogues of sulfones—hold significant potential as leads in discovery chemistry, yet their application in this arena has been held back by the scarcity of appropriate synthetic routes. Existing methods employ sulfides as substrates, and rely on consecutive imination reactions using the hazardous reagent O-mesitylenesulfonyl hydroxylamine. Here we report a method for sulfondiimine synthesis that does not begin with a sulfide or a thiol, and instead employs two Grignard reagents and a bespoke sulfinylamine (R—N═S═O) reagent as starting materials. Lewis acid-mediated assembly of these three components provides efficient access to a series of sulfilimine intermediates. A novel rhodium-catalyzed imination of these electron-rich sulfilimines then delivers a varied range of sulfondiimines featuring orthogonal N-functionalization. Conditions for the selective manipulation of both N-atoms of the sulfondiimines are reported, allowing access to a broad range of mono- and difunctionalized products. The oxidation of the sulfilimine intermediates is also described, and provides a complementary route to sulfoximines. |
| first_indexed | 2024-03-07T02:52:59Z |
| format | Journal article |
| id | oxford-uuid:ae51dde3-701e-4cc3-b3db-73631f1b4007 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T02:52:59Z |
| publishDate | 2019 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:ae51dde3-701e-4cc3-b3db-73631f1b40072022-03-27T03:41:43ZModular sulfondiimine synthesis using a stable sulfinylamine reagentJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ae51dde3-701e-4cc3-b3db-73631f1b4007Symplectic Elements at OxfordAmerican Chemical Society2019Zhang, ZDavies, TWillis, MSulfondiimines—the double aza-analogues of sulfones—hold significant potential as leads in discovery chemistry, yet their application in this arena has been held back by the scarcity of appropriate synthetic routes. Existing methods employ sulfides as substrates, and rely on consecutive imination reactions using the hazardous reagent O-mesitylenesulfonyl hydroxylamine. Here we report a method for sulfondiimine synthesis that does not begin with a sulfide or a thiol, and instead employs two Grignard reagents and a bespoke sulfinylamine (R—N═S═O) reagent as starting materials. Lewis acid-mediated assembly of these three components provides efficient access to a series of sulfilimine intermediates. A novel rhodium-catalyzed imination of these electron-rich sulfilimines then delivers a varied range of sulfondiimines featuring orthogonal N-functionalization. Conditions for the selective manipulation of both N-atoms of the sulfondiimines are reported, allowing access to a broad range of mono- and difunctionalized products. The oxidation of the sulfilimine intermediates is also described, and provides a complementary route to sulfoximines. |
| spellingShingle | Zhang, Z Davies, T Willis, M Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title | Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title_full | Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title_fullStr | Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title_full_unstemmed | Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title_short | Modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| title_sort | modular sulfondiimine synthesis using a stable sulfinylamine reagent |
| work_keys_str_mv | AT zhangz modularsulfondiiminesynthesisusingastablesulfinylaminereagent AT daviest modularsulfondiiminesynthesisusingastablesulfinylaminereagent AT willism modularsulfondiiminesynthesisusingastablesulfinylaminereagent |