Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors
We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double CC/CO arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most...
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| مؤلفون آخرون: | , , , , , |
| التنسيق: | article |
| منشور في: |
2025
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://dx.doi.org/10.1016/j.jorganchem.2025.123526 https://www.sciencedirect.com/science/article/pii/S0022328X25000208 http://hdl.handle.net/10576/64075 |
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| _version_ | 1857415087474606080 |
|---|---|
| author | Raed M., Al-Zoubi |
| author2 | Al-Jammal, Walid K. Shkoor, Mohanad Bani-Yaseen, Abdulilah D. Khan, Abbas Agouni, Abdelali McDonald, Robert |
| author2_role | author author author author author author |
| author_facet | Raed M., Al-Zoubi Al-Jammal, Walid K. Shkoor, Mohanad Bani-Yaseen, Abdulilah D. Khan, Abbas Agouni, Abdelali McDonald, Robert |
| author_role | author |
| dc.creator.none.fl_str_mv | Raed M., Al-Zoubi Al-Jammal, Walid K. Shkoor, Mohanad Bani-Yaseen, Abdulilah D. Khan, Abbas Agouni, Abdelali McDonald, Robert |
| dc.date.none.fl_str_mv | 2025-04-08T10:14:03Z 2025-01-21 |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://dx.doi.org/10.1016/j.jorganchem.2025.123526 Al-Zoubi, R. M., Al-Jammal, W. K., Shkoor, M., Bani-Yaseen, A. D., Khan, A., Agouni, A., & McDonald, R. (2025). Regioselective Domino C–C/C–O Arylation of 1, 2, 3-Triiodobenzenes and 1, 3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo [b] furan as Potential ALK Inhibitors. Journal of Organometallic Chemistry, 123526. 0022-328X https://www.sciencedirect.com/science/article/pii/S0022328X25000208 http://hdl.handle.net/10576/64075 1028 1872-8561 |
| dc.language.none.fl_str_mv | en |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.rights.none.fl_str_mv | http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |
| dc.title.none.fl_str_mv | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| dc.type.none.fl_str_mv | Article info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | We report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double CC/CO arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most reactive and least sterically hindered. The O-arylation reactions were selectively performed with the more reactive carbonyl group. This domino process demonstrated excellent substrate tolerance. Under optimized conditions, the reaction of electron-deficient 1,2,3-triiodoarenes with dicarbonyl compounds afforded the highest isolated yields. Furthermore, the designed novel compounds were screened against ALK, revealing that among the 17 tested, ALK-9p, ALK-9b, ALK-9n, and ALK-9m exhibited the best docking scores using the extra-precision docking method. Molecular simulations of these compounds with ALK confirmed their stable binding behavior, compact topology, and minimal residue flexibility. Finally, binding free energy calculations using MM/PBSA and MM/GBSA methods further validated the pharmacological potential of these shortlisted hits as ALK inhibitors. These results demand prompt experimental validation to determine the promising clinical applications of these compounds in the management of cancer |
| eu_rights_str_mv | openAccess |
| format | article |
| id | qu_4ef0d7d198f55bc5ef1577d19652c34a |
| identifier_str_mv | Al-Zoubi, R. M., Al-Jammal, W. K., Shkoor, M., Bani-Yaseen, A. D., Khan, A., Agouni, A., & McDonald, R. (2025). Regioselective Domino C–C/C–O Arylation of 1, 2, 3-Triiodobenzenes and 1, 3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo [b] furan as Potential ALK Inhibitors. Journal of Organometallic Chemistry, 123526. 0022-328X 1028 1872-8561 |
| language_invalid_str_mv | en |
| network_acronym_str | qu |
| network_name_str | Qatar University repository |
| oai_identifier_str | oai:qspace.qu.edu.qa:10576/64075 |
| publishDate | 2025 |
| publisher.none.fl_str_mv | Elsevier |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| spelling | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitorsRaed M., Al-ZoubiAl-Jammal, Walid K.Shkoor, MohanadBani-Yaseen, Abdulilah D.Khan, AbbasAgouni, AbdelaliMcDonald, RobertBenzofuranIodinationArylationC-C couplingC-O couplingSubstituent effectRegioselectivityWe report a simple, direct, and regioselective protocol for the synthesis of 2,3-disubstituted 7-iodobenzo[b]furans via domino double CC/CO arylations of 1,2,3-triiodobenzene and 1,3-dicarbonyl compounds. Remarkably, the C-arylation occurred exclusively at the terminal positions, which are the most reactive and least sterically hindered. The O-arylation reactions were selectively performed with the more reactive carbonyl group. This domino process demonstrated excellent substrate tolerance. Under optimized conditions, the reaction of electron-deficient 1,2,3-triiodoarenes with dicarbonyl compounds afforded the highest isolated yields. Furthermore, the designed novel compounds were screened against ALK, revealing that among the 17 tested, ALK-9p, ALK-9b, ALK-9n, and ALK-9m exhibited the best docking scores using the extra-precision docking method. Molecular simulations of these compounds with ALK confirmed their stable binding behavior, compact topology, and minimal residue flexibility. Finally, binding free energy calculations using MM/PBSA and MM/GBSA methods further validated the pharmacological potential of these shortlisted hits as ALK inhibitors. These results demand prompt experimental validation to determine the promising clinical applications of these compounds in the management of cancerThe Deanship of Research at Jordan University of Science and Technology (JUST) has provided funding for this project (Grant No. 834/2018 ) and Qatar University (Grants No. QUT2RP-CPH-24/25-477 and QUPD-CPH-23/24-592 ).Elsevier2025-04-08T10:14:03Z2025-01-21Articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1016/j.jorganchem.2025.123526Al-Zoubi, R. M., Al-Jammal, W. K., Shkoor, M., Bani-Yaseen, A. D., Khan, A., Agouni, A., & McDonald, R. (2025). Regioselective Domino C–C/C–O Arylation of 1, 2, 3-Triiodobenzenes and 1, 3-Diketones: Synthesis and In Silico Evaluation of 7-Iodobenzo [b] furan as Potential ALK Inhibitors. Journal of Organometallic Chemistry, 123526.0022-328Xhttps://www.sciencedirect.com/science/article/pii/S0022328X25000208http://hdl.handle.net/10576/6407510281872-8561enhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:qspace.qu.edu.qa:10576/640752025-04-08T19:05:49Z |
| spellingShingle | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors Raed M., Al-Zoubi Benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |
| status_str | publishedVersion |
| title | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| title_full | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| title_fullStr | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| title_full_unstemmed | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| title_short | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| title_sort | Regioselective domino C–C/C–O arylation of 1,2,3-triiodobenzenes and 1,3-diketones: Synthesis and in silico evaluation of 7-iodobenzo[b]furan as potential ALK inhibitors |
| topic | Benzofuran Iodination Arylation C-C coupling C-O coupling Substituent effect Regioselectivity |
| url | http://dx.doi.org/10.1016/j.jorganchem.2025.123526 https://www.sciencedirect.com/science/article/pii/S0022328X25000208 http://hdl.handle.net/10576/64075 |