Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups
Abstract Sulfur‐containing functional groups (SFGs) are increasingly important for modern medicinal chemistry and their large structural diversity provides many opportunities for lead optimization. In an effort to simplify the access to the full set of SFGs, we report herein a versatile strategy uti...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley-VCH
2024-11-01
|
| Series: | ChemistryEurope |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ceur.202400053 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846169756742189056 |
|---|---|
| author | Yue Liu Dr. Takashi Okazoe Dr. Tim Gatzenmeier Prof. Dr. Kyoko Nozaki |
| author_facet | Yue Liu Dr. Takashi Okazoe Dr. Tim Gatzenmeier Prof. Dr. Kyoko Nozaki |
| author_sort | Yue Liu |
| collection | DOAJ |
| description | Abstract Sulfur‐containing functional groups (SFGs) are increasingly important for modern medicinal chemistry and their large structural diversity provides many opportunities for lead optimization. In an effort to simplify the access to the full set of SFGs, we report herein a versatile strategy utilizing (hetero)aryl trityl sulfides (ArSCPh3) as the common precursors. We developed a mild and high yielding Pd‐catalyzed thiotritylation cross‐coupling methodology to afford ArSCPh3 compounds from (hetero)aryl bromides and iodides. Efficient chemoselective derivatizations provided access to eight different SFGs and sulfur(VI) fluorine exchange (SuFEx) hubs, which open up further downstream derivatizations towards the full set of SFGs. Thereby obtainable sulfur motifs include aryl sulfur pentafluorides (ArSF5), aryl tetrafluoro‐λ6‐sulfanyl chlorides (ArSF4Cl), aryl sulfonimidoyl fluorides (ArS(O)(NR)F), aryl sulfonyl fluorides (ArSO2F), aryl sulfonic acids (ArSO3H), and aryl sulfinyl fluorides (ArSOF), which are all valuable functional groups in modern drug discovery. |
| format | Article |
| id | doaj-art-bec70674f1e74649a1d90a28e13b25bd |
| institution | Kabale University |
| issn | 2751-4765 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | ChemistryEurope |
| spelling | doaj-art-bec70674f1e74649a1d90a28e13b25bd2024-11-12T09:17:45ZengWiley-VCHChemistryEurope2751-47652024-11-0126n/an/a10.1002/ceur.202400053Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional GroupsYue Liu0Dr. Takashi Okazoe1Dr. Tim Gatzenmeier2Prof. Dr. Kyoko Nozaki3Department of Chemistry and Biotechnology Graduate School of Engineering The University of Tokyo 2-11-16 Yayoi Bunkyo-Ku, Tokyo 113-0032 JapanDepartment of Chemistry and Biotechnology Graduate School of Engineering The University of Tokyo 2-11-16 Yayoi Bunkyo-Ku, Tokyo 113-0032 JapanDepartment of Chemistry and Biotechnology Graduate School of Engineering The University of Tokyo 2-11-16 Yayoi Bunkyo-Ku, Tokyo 113-0032 JapanDepartment of Chemistry and Biotechnology Graduate School of Engineering The University of Tokyo 2-11-16 Yayoi Bunkyo-Ku, Tokyo 113-0032 JapanAbstract Sulfur‐containing functional groups (SFGs) are increasingly important for modern medicinal chemistry and their large structural diversity provides many opportunities for lead optimization. In an effort to simplify the access to the full set of SFGs, we report herein a versatile strategy utilizing (hetero)aryl trityl sulfides (ArSCPh3) as the common precursors. We developed a mild and high yielding Pd‐catalyzed thiotritylation cross‐coupling methodology to afford ArSCPh3 compounds from (hetero)aryl bromides and iodides. Efficient chemoselective derivatizations provided access to eight different SFGs and sulfur(VI) fluorine exchange (SuFEx) hubs, which open up further downstream derivatizations towards the full set of SFGs. Thereby obtainable sulfur motifs include aryl sulfur pentafluorides (ArSF5), aryl tetrafluoro‐λ6‐sulfanyl chlorides (ArSF4Cl), aryl sulfonimidoyl fluorides (ArS(O)(NR)F), aryl sulfonyl fluorides (ArSO2F), aryl sulfonic acids (ArSO3H), and aryl sulfinyl fluorides (ArSOF), which are all valuable functional groups in modern drug discovery.https://doi.org/10.1002/ceur.202400053thiolation cross-couplingsulfur functional groupsPd catalysisSuFEx chemistrydrug derivatization |
| spellingShingle | Yue Liu Dr. Takashi Okazoe Dr. Tim Gatzenmeier Prof. Dr. Kyoko Nozaki Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups ChemistryEurope thiolation cross-coupling sulfur functional groups Pd catalysis SuFEx chemistry drug derivatization |
| title | Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups |
| title_full | Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups |
| title_fullStr | Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups |
| title_full_unstemmed | Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups |
| title_short | Pd‐Catalyzed Thiotritylation Cross‐Coupling of Aryl Bromides and Iodides to Access Sulfur Functional Groups |
| title_sort | pd catalyzed thiotritylation cross coupling of aryl bromides and iodides to access sulfur functional groups |
| topic | thiolation cross-coupling sulfur functional groups Pd catalysis SuFEx chemistry drug derivatization |
| url | https://doi.org/10.1002/ceur.202400053 |
| work_keys_str_mv | AT yueliu pdcatalyzedthiotritylationcrosscouplingofarylbromidesandiodidestoaccesssulfurfunctionalgroups AT drtakashiokazoe pdcatalyzedthiotritylationcrosscouplingofarylbromidesandiodidestoaccesssulfurfunctionalgroups AT drtimgatzenmeier pdcatalyzedthiotritylationcrosscouplingofarylbromidesandiodidestoaccesssulfurfunctionalgroups AT profdrkyokonozaki pdcatalyzedthiotritylationcrosscouplingofarylbromidesandiodidestoaccesssulfurfunctionalgroups |