[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-121152-en":3,"doc-seo-121152-105":30,"detail-sidebar-cat-0-en-105":91},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":4,"category_id":11,"category_name":12,"doc_title":13,"doc_description":14,"doc_content":15,"file_id":16,"file_url":17,"file_type":18,"file_size":19,"view_count":20,"is_deleted":4,"is_public":20,"is_downloadable":20,"audit_status":20,"page_count":21,"language":22,"language_code":23,"site_id":24,"html_lang":23,"table_of_contents":25,"faqs":26,"seo_title":27,"seo_description":14,"update_tm":28,"read_time":29},121152,1099514068035,"Ezra","https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c",8,"Research & Report","Hybrid Machine Learning Approach to Predict the Site Selectivity of Iridium-Catalyzed Arene Borylation","Arene and heteroarene C–H borylation enables site-selective functionalization of complex molecules, yet predicting which C–H bond undergoes borylation is difficult when multiple arenes compete. A hybrid model, combining density functional theory, semiempirical quantum mechanics, cheminformatics, linear regression, and machine learning, predicts Site of Borylation and extrapolates to new chemical space. Experimental validation shows higher accuracy than prior machine-learning models or human experts, supporting experiment design in pharmaceutical development.","UC Berkeley  \nUC Berkeley Previously Published Works  \nTitle  \nHybrid Machine Learning Approach to Predict the Site Selectivity of Iridium-Catalyzed Arene Borylation  \nPermalink  \n[https://escholarship.org/uc/item/7dc6w83w](https://escholarship.org/uc/item/7dc6w83w)  \nJournal  \nJournal of the American Chemical Society, 145(31)  \nISSN  \n0002-7863  \nAuthors  \nCaldeweyher, Eike  \nElkin, Masha Gheibi, Golsa et al.  \nPublication Date  \n2023-08-09  \nDOI  \n10.1021/jacs.3c04986  \nPeer reviewed  \n[eScholarship.org](eScholarship.org) Powered by the California Digital Library  \nUniversity of California  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \n\n|  | HHS Public Access\u003Cbr>Author manuscript\u003Cbr>J Am Chem Soc. Author manuscript; available in PMC 2025 January 10. |\n| --- | --- |\n\nPublished in final edited form as:  \nJ Am Chem Soc. 2023 August 09; 145(31): 17367–17376. doi:10.1021/jacs.3c04986 .  \nHybrid Machine Learning Approach to Predict the Site Selectivity of Iridium-Catalyzed Arene Borylation  \nEike Caldeweyher\\# ,  \nData Science & Modelling, Pharmaceutical Sciences, R&D, AstraZeneca Gothenburg, SE-431 83 Mölndal, Sweden  \nMasha Elkin\\# ,  \nDepartment of Chemistry, University of California, Berkeley, California 94720, United States  \nGolsa Gheibi,  \nDepartment of Chemistry, University of California, Berkeley, California 94720, United States  \nMagnus Johansson,  \nCardiovascular, Renal and Metabolism, Biopharmaceuticals R&D, AstraZeneca Gothenburg, SE-431 83 Mölndal, Sweden; Department of Organic Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden  \nChristian Sköld,  \nDrug Design and Discovery, Department of Medicinal Chemistry, Uppsala University, SE-751 23 Uppsala, Sweden  \nPer-Ola Norrby,  \nData Science & Modelling, Pharmaceutical Sciences, R&D, AstraZeneca Gothenburg, SE-431 83 Mölndal, Sweden  \nJohn F. Hartwig  \nDepartment of Chemistry, University of California, Berkeley, California 94720, United States  \nAbstract  \nThe borylation of aryl and heteroaryl C–H bonds is valuable for the site-selective functionalization ofC–H bonds in complex molecules. Iridium catalysts ligated by bipyridine ligands catalyze the borylation of the C–H bond that is most acidic and least sterically hindered in an arene, but predicting the site of borylation in molecules containing multiple arenes is difficult. To address  \nCorresponding Authors: Per-Ola Norrby – Data Science & Modelling, Pharmaceutical Sciences, R&D, AstraZeneca Gothenburg,  \nSE-431 83 Mölndal, Sweden; [per-ola.norrby@astrazeneca.com](per-ola.norrby@astrazeneca.com), John F. Hartwig – Department of Chemistry, University of Ca\\# Alifouthnria,CoBerkeleyntributio,nCalifornias 94720, United States; [jhartwig@berkeley.edu](jhartwig@berkeley.edu).  \nE.C. and M.E. contributed equally to this work. All authors conceptualized the project and designed experiments.  \nThe authors declare no competing financial interest.  \nASSOCIATED CONTENT Supporting Information  \nThe Supporting Information is available free of charge at [https://pubs.acs.org/doi/10.1021/jacs.3c04986](https://pubs.acs.org/doi/10.1021/jacs.3c04986) .  \nAll experimental procedures, details of the computational workflow, and human survey results (PDF)  \nNP model statistics (XLSX)  \nPLS model statistics (XLSX)  \nAuthor Manuscr ipt Author Manuscr ipt Author Manuscr ipt Author Manuscript  \nCaldeweyher et al. Page 2  \nthis challenge, we report a hybrid computational model that predicts the Site of Borylation (SoBo) in complex molecules. The SoBo model combines density functional theory, semiempirical quantum mechanics, cheminformatics, linear regression, and machine learning to predict site selectivity and to extrapolate these predictions to new chemical space. Experimental validation of SoBo showed that the model predicts the major site of borylation of pharmaceutical intermediates with higher accuracy than prior machine-learning models or human experts, demonstrating that SoBo will be useful to g","cbCailXNwPsdcG0I","https://ap.wps.com/l/cbCailXNwPsdcG0I","pdf",1538283,1,19,"English","en",105,"# Abstract\n# Introduction\n## Challenge in site-selective C–H borylation\n## Hybrid computational model approach\n## Experimental validation and application","[{\"question\":\"Why is predicting site selectivity in iridium-catalyzed arene borylation difficult?\",\"answer\":\"Because molecules can contain multiple arenes and many competing chemical factors affect relative reaction rates, making site outcomes hard to forecast with simple heuristics.\"},{\"question\":\"What components are combined in the reported hybrid model?\",\"answer\":\"The model integrates density functional theory, semiempirical quantum mechanics, cheminformatics, linear regression, and machine learning to predict Site of Borylation and extrapolate to new chemical space.\"},{\"question\":\"How does the SoBo model perform compared with prior models or human experts?\",\"answer\":\"Experimental validation indicates the model predicts the major borylation site of pharmaceutical intermediates with higher accuracy than previous machine-learning models or human experts.\"}]","Hybrid Machine Learning Approach to Predict the Site Selectivity of Iridium-Catalyzed Arene Borylation | PDF",1785734114,48,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":13,"keywords":34,"description":14,"schema_data":35,"social_meta":86,"head_meta":88,"extra_data":90,"updated_unix":28},"hybrid-machine-learning-approach-to-predict-the-site-selectivity-of-iridium-catalyzed-arene-borylation","",{"@graph":36,"@context":85},[37,54,68],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,51],{"item":41,"name":42,"@type":43,"position":20},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/document/","Document",2,{"item":49,"name":12,"@type":43,"position":50},"https://docshare.wps.com/document/research-report/",3,{"item":52,"name":13,"@type":43,"position":53},"https://docshare.wps.com/document/hybrid-machine-learning-approach-to-predict-the-site-selectivity-of-iridium-catalyzed-arene-borylation/121152/",4,{"url":52,"name":13,"@type":55,"author":56,"headline":13,"publisher":58,"fileFormat":61,"inLanguage":23,"description":14,"dateModified":62,"datePublished":62,"encodingFormat":61,"isAccessibleForFree":63,"interactionStatistic":64},"DigitalDocument",{"name":9,"@type":57},"Person",{"url":41,"name":59,"@type":60},"DocShare","Organization","application/pdf","2026-08-03",true,{"@type":65,"interactionType":66,"userInteractionCount":20},"InteractionCounter",{"@type":67},"ViewAction",{"@type":69,"mainEntity":70},"FAQPage",[71,77,81],{"name":72,"@type":73,"acceptedAnswer":74},"Why is predicting site selectivity in iridium-catalyzed arene borylation difficult?","Question",{"text":75,"@type":76},"Because molecules can contain multiple arenes and many competing chemical factors affect relative reaction rates, making site outcomes hard to forecast with simple heuristics.","Answer",{"name":78,"@type":73,"acceptedAnswer":79},"What components are combined in the reported hybrid model?",{"text":80,"@type":76},"The model integrates density functional theory, semiempirical quantum mechanics, cheminformatics, linear regression, and machine learning to predict Site of Borylation and extrapolate to new chemical space.",{"name":82,"@type":73,"acceptedAnswer":83},"How does the SoBo model perform compared with prior models or human experts?",{"text":84,"@type":76},"Experimental validation indicates the model predicts the major borylation site of pharmaceutical intermediates with higher accuracy than previous machine-learning models or human experts.","https://schema.org",{"og:url":52,"og:type":87,"og:title":13,"og:site_name":59,"og:description":14},"article",{"robots":89,"canonical":52},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":92},[93,97,101,105,110,115,120,123,128,131,135],{"id":20,"doc_module":4,"doc_module_name":46,"category_name":94,"show_sort_weight":95,"slug":96},"Story & Novel",90,"story-novel",{"id":47,"doc_module":4,"doc_module_name":46,"category_name":98,"show_sort_weight":99,"slug":100},"Literature",80,"literature",{"id":53,"doc_module":4,"doc_module_name":46,"category_name":102,"show_sort_weight":103,"slug":104},"Exam",70,"exam",{"id":106,"doc_module":4,"doc_module_name":46,"category_name":107,"show_sort_weight":108,"slug":109},5,"Comic",60,"comic",{"id":111,"doc_module":4,"doc_module_name":46,"category_name":112,"show_sort_weight":113,"slug":114},6,"Technology",50,"technology",{"id":116,"doc_module":4,"doc_module_name":46,"category_name":117,"show_sort_weight":118,"slug":119},7,"Healthcare",40,"healthcare",{"id":11,"doc_module":4,"doc_module_name":46,"category_name":12,"show_sort_weight":121,"slug":122},30,"research-report",{"id":124,"doc_module":4,"doc_module_name":46,"category_name":125,"show_sort_weight":126,"slug":127},9,"Religion & Spirituality",20,"religion-spirituality",{"id":126,"doc_module":4,"doc_module_name":46,"category_name":129,"show_sort_weight":126,"slug":130},"World Cup","world-cup",{"id":132,"doc_module":4,"doc_module_name":46,"category_name":133,"show_sort_weight":132,"slug":134},10,"Lifestyle","lifestyle",{"id":21,"doc_module":4,"doc_module_name":46,"category_name":136,"show_sort_weight":106,"slug":137},"General","general"]