Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides
Sulfoximines and sulfonimidamides are promising compounds for medicinal and agrochemistry. As monoaza analogues of sulfones and sulfonamides, respectively, they combine good physicochemical properties, high stability, and the ability to build complexity from a three-dimensional core. However, a lack...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
American Chemical Society
2020
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| _version_ | 1826282411887951872 |
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| author | Davies, TQ Tilby, MJ Ren, J Parker, NA Skolc, D Hall, A Duarte, F Willis, MC |
| author_facet | Davies, TQ Tilby, MJ Ren, J Parker, NA Skolc, D Hall, A Duarte, F Willis, MC |
| author_sort | Davies, TQ |
| collection | OXFORD |
| description | Sulfoximines and sulfonimidamides are promising compounds for medicinal and agrochemistry. As monoaza analogues of sulfones and sulfonamides, respectively, they combine good physicochemical properties, high stability, and the ability to build complexity from a three-dimensional core. However, a lack of quick and efficient methods to prepare these compounds has hindered their uptake in molecule discovery programmes. Herein, we describe a unified, one-pot approach to both sulfoximines and sulfonimidamides, which exploits the high electrophilicity of sulfinyl nitrenes. We generate these rare reactive intermediates from a novel sulfinylhydroxylamine (R–O–N=S=O) reagent through an N–O bond fragmentation process. Combining sulfinyl nitrenes with carbon and nitrogen nucleophiles enables the synthesis of sulfoximines and sulfonimidamides in a reaction time of just 15 min. Alkyl, (hetero)aryl, and alkenyl organometallic reagents can all be used as the first or second component in the reaction, while primary and secondary amines, and anilines, all react with high efficiency as the second nucleophile. The tolerance of the reaction to steric and electronic factors has allowed for the synthesis of the most diverse set of sulfoximines and sulfonimidamides yet described. Experimental and computational investigations support the intermediacy of sulfinyl nitrenes, with nitrene formation proceeding via a transient triplet intermediate before reaching a planar singlet species. |
| first_indexed | 2024-03-07T00:43:27Z |
| format | Journal article |
| id | oxford-uuid:83d77de3-b317-4755-9453-ccf610bccf8b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:43:27Z |
| publishDate | 2020 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:83d77de3-b317-4755-9453-ccf610bccf8b2022-03-26T21:47:02ZHarnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamidesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:83d77de3-b317-4755-9453-ccf610bccf8bEnglishSymplectic ElementsAmerican Chemical Society2020Davies, TQTilby, MJRen, JParker, NASkolc, DHall, ADuarte, FWillis, MCSulfoximines and sulfonimidamides are promising compounds for medicinal and agrochemistry. As monoaza analogues of sulfones and sulfonamides, respectively, they combine good physicochemical properties, high stability, and the ability to build complexity from a three-dimensional core. However, a lack of quick and efficient methods to prepare these compounds has hindered their uptake in molecule discovery programmes. Herein, we describe a unified, one-pot approach to both sulfoximines and sulfonimidamides, which exploits the high electrophilicity of sulfinyl nitrenes. We generate these rare reactive intermediates from a novel sulfinylhydroxylamine (R–O–N=S=O) reagent through an N–O bond fragmentation process. Combining sulfinyl nitrenes with carbon and nitrogen nucleophiles enables the synthesis of sulfoximines and sulfonimidamides in a reaction time of just 15 min. Alkyl, (hetero)aryl, and alkenyl organometallic reagents can all be used as the first or second component in the reaction, while primary and secondary amines, and anilines, all react with high efficiency as the second nucleophile. The tolerance of the reaction to steric and electronic factors has allowed for the synthesis of the most diverse set of sulfoximines and sulfonimidamides yet described. Experimental and computational investigations support the intermediacy of sulfinyl nitrenes, with nitrene formation proceeding via a transient triplet intermediate before reaching a planar singlet species. |
| spellingShingle | Davies, TQ Tilby, MJ Ren, J Parker, NA Skolc, D Hall, A Duarte, F Willis, MC Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title | Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title_full | Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title_fullStr | Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title_full_unstemmed | Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title_short | Harnessing sulfinyl nitrenes: a unified one-pot synthesis of sulfoximines and sulfonimidamides |
| title_sort | harnessing sulfinyl nitrenes a unified one pot synthesis of sulfoximines and sulfonimidamides |
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