Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions
Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functi...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Published: |
American Chemical Society
2018
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| _version_ | 1826259320060248064 |
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| author | Markovic, T Murray, P Rocke, B Shavnya, A Blakemore, D Willis, M |
| author_facet | Markovic, T Murray, P Rocke, B Shavnya, A Blakemore, D Willis, M |
| author_sort | Markovic, T |
| collection | OXFORD |
| description | Heterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant to the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents, and when treated with a Pd(0)-catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, the pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents. |
| first_indexed | 2024-03-06T18:47:59Z |
| format | Journal article |
| id | oxford-uuid:0f32f36f-fbe0-497a-92ca-2e21f89c2f11 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T18:47:59Z |
| publishDate | 2018 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:0f32f36f-fbe0-497a-92ca-2e21f89c2f112022-03-26T09:49:57ZHeterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0f32f36f-fbe0-497a-92ca-2e21f89c2f11Symplectic Elements at OxfordAmerican Chemical Society2018Markovic, TMurray, PRocke, BShavnya, ABlakemore, DWillis, MHeterocyclic sulfinates are effective reagents in palladium-catalyzed coupling reactions with aryl and heteroaryl halides, often providing high yields of the targeted biaryl. However, the preparation and purification of complex heterocylic sulfinates can be problematic. In addition, sulfinate functionality is not tolerant to the majority of synthetic transformations, making these reagents unsuitable for multistep elaboration. Herein, we show that heterocyclic allylsulfones can function as latent sulfinate reagents, and when treated with a Pd(0)-catalyst and an aryl halide, undergo deallylation, followed by efficient desulfinylative cross-coupling. A broad range of allyl heteroarylsulfones are conveniently prepared, using several complementary routes, and are shown to be effective coupling partners with a variety of aryl and heteroaryl halides. We demonstrate that the allylsulfone functional group can tolerate a range of standard synthetic transformations, including orthogonal C- and N-coupling reactions, allowing multistep elaboration. The allylsulfones are successfully coupled with a variety of medicinally relevant substrates, demonstrating their applicability in demanding cross-coupling transformations. In addition, the pharmaceutical agents crizotinib and etoricoxib were prepared using allyl heteroaryl sulfone coupling partners, further demonstrating the utility of these new reagents. |
| spellingShingle | Markovic, T Murray, P Rocke, B Shavnya, A Blakemore, D Willis, M Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title | Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title_full | Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title_fullStr | Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title_full_unstemmed | Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title_short | Heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium-catalyzed cross-coupling reactions |
| title_sort | heterocyclic allylsulfones as latent heteroaryl nucleophiles in palladium catalyzed cross coupling reactions |
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