[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-detail-174005-en":3,"doc-seo-174005-105":30,"detail-sidebar-cat-1-en-105":90},{"code":4,"msg":5,"data":6},0,"success",{"doc_id":7,"user_id":8,"nickname":9,"user_avatar":10,"doc_module":11,"category_id":12,"category_name":13,"doc_title":14,"doc_description":15,"doc_content":16,"file_id":17,"file_url":18,"file_type":19,"file_size":20,"view_count":4,"is_deleted":4,"is_public":11,"is_downloadable":11,"audit_status":11,"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":15,"update_tm":28,"read_time":29},174005,962084925290,"Caleb Sterling","https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45",1,158,"General","Enantioselective construction of a congested quaternary stereogenic center in isoindolinones bearing three aryl groups - Abstract","Enantioselective construction of a congested quaternary stereogenic center with three aryl groups in isoindolinone derivatives is achieved through an efficient formal Betti reaction. The method uses phenols and diaryl ketimines generated in situ from isoindolinone alcohols. Catalysis by a chiral phosphoric acid enables a broad range of ketimines and phenols to react, affording products in high yields with strong regioselectivity and enantioselectivity, delivering stereochemically complex isoindolinone scaffolds.","Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia. E-mail: \u0013 HYPERLINK \"mailto:matija.gredicak@irb.hr\" \u0014matija.gredicak@irb.hr\u0015\nState Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China. E-mail: \u0013 HYPERLINK \"mailto:slyou@sioc.ac.cn\" \u0014slyou@sioc.ac.cn\u0015\nElectronic Supplementary Information (ESI) available: [details of any supplementary information available should be included here]. See DOI: 10.1039/x0xx00000x\nReceived 00th January 20xx,\nAccepted 00th January 20xx\nDOI: 10.1039/x0xx00000x\n\u000eEnantioselective construction of a congested quaternary stereogenic center in isoindolinones bearing three aryl groups via an organocatalytic formal Betti reaction\nArben Beriša,a Danijel Glavač,a Chao Zheng,b Shu-Li Youb* and Matija Gredičaka*\nAn efficient enantioselective formal Betti reaction between phenols and diaryl ketimines generated in situ from isoindolinone alcohols is described. In a reaction catalyzed by a chiral phosphoric acid, a broad range of ketimines and phenols afforded isoindolinone derivatives comprising a congested quaternary stereogenic center bearing three aryl groups in high yields, and high regioselectivities and enantioselectivities.\nIntroduction\nArylation of benzophenone-derived ketimines is the most effective and straightforward route towards the construction of a quaternary stereogenic center bearing three phenyl rings. The scarcity of reported methodologies stems from the remarkably low reactivity of bis-aromatic ketimines, and from the inherent difficulty for the catalyst to control the enantioselectivity due to the lack of sufficient steric difference between two phenyl rings. Hence, only few notable examples of asymmetric arylations of diaryl ketimines have been reported to date.\nIn 2012, Hayashi and Nishimura developed an enantioselective arylation of saccharin-derived cyclic ketimines with arylboroxines in the presence of a chiral rhodium complex.1 Following this seminal work, several rhodium2 and palladium3 catalyzed asymmetric arylations of cyclic N-sulfonyl diaryl ketimines have been reported in the literature. In contrast to these elegant examples on transition-metal catalysis, their organocatalytic counterparts are virtually non-existent in the literature. Although asymmetric organocatalytic additions of phenyl-derived nucleophiles to aldimines are well known,4 reports on their additions to ketimines are rather scarce in the literature.5 Reported strategies usually employ naphthol derivatives as nucleophiles, and isatine-derived ketimines as electrophiles (Scheme 1).6\nIn this context, seminal report by Pedro describes quinine-thiourea catalyzed addition of naphthols and electron-rich phenols to isatin derived ketimines.6a The same type of nucleophile was utilized in the quinine-squaramide catalyzed addition to quinazoline-type cyclic trifluoromethyl ketimines reported by Wang and Xie.6d In 2020, Li developed regio- and enantioselective addition of electron-rich phenols to isatin-derived ketimines.7 However, to the best of our knowledge, there are no reports on the asymmetric organocatalytic methodologies for the construction of quaternary centers of chirality bearing three phenyl rings.\n\u0013 EMBED ChemDraw.Document.6.0 \u0014\n\u0015\nScheme 1. Enantioselective organocatalytic additions of phenol derivatives to ketimines for the generation of tetrasubstituted stereogenic centers.\nOn the other hand, 3,3-disubstituted isoindolinones are core structural skeletons embedded in many natural products and biologically active compounds (Scheme 2).8 Their biological activities are greatly influenced by the type of substituents and absolute configuration on this position. Hence, it is not surprising that the stereoselective synthesis of chiral isoindolinone derivatives – particularly the ones possessing quaternary stereogenic center – has received a lot of attention i","cbCaiflcpM1Dwp16","https://ap.wps.com/l/cbCaiflcpM1Dwp16","docx",5181639,8,"English","en",105,"# Introduction\n## Background and limitations\n## Prior transition-metal and organocatalytic work\n## Structural relevance of isoindolinones\n# Results and discussion\n## Chiral phosphoric acid screening and optimization","[{\"question\":\"What is the key transformation described in the document?\",\"answer\":\"An efficient enantioselective formal Betti reaction forms isoindolinone derivatives via reactions between phenols and diaryl ketimines generated in situ from isoindolinone alcohols.\"},{\"question\":\"Which catalyst class is used to achieve enantioselectivity?\",\"answer\":\"A chiral phosphoric acid catalyzes the reaction, enabling high enantioselectivity and regioselectivity across a range of substrates.\"},{\"question\":\"How do catalyst substituents affect the enantiomeric outcome?\",\"answer\":\"Changing substituents on the chiral phosphoric acid impacts enantioselectivity; some bulkier or differently positioned groups reduce enantiomeric ratios, while certain aromatic substitutions improve enantioselective purity.\"}]","Enantioselective construction of a congested quaternary stereogenic center in isoindolinones bearing three aryl groups - Abstract | DOCX",1788309125,3,{"code":4,"msg":31,"data":32},"ok",{"site_id":24,"language":23,"slug":33,"title":14,"keywords":34,"description":15,"schema_data":35,"social_meta":85,"head_meta":87,"extra_data":89,"updated_unix":28},"enantioselective-construction-of-a-congested-quaternary-stereogenic-center-in-isoindolinones-bearing-three-aryl-groups-abstract","",{"@graph":36,"@context":84},[37,53,67],{"@type":38,"itemListElement":39},"BreadcrumbList",[40,44,48,50],{"item":41,"name":42,"@type":43,"position":11},"https://docshare.wps.com","Home","ListItem",{"item":45,"name":46,"@type":43,"position":47},"https://docshare.wps.com/template/","Template",2,{"item":49,"name":13,"@type":43,"position":29},"https://docshare.wps.com/template/general/",{"item":51,"name":14,"@type":43,"position":52},"https://docshare.wps.com/template/enantioselective-construction-of-a-congested-quaternary-stereogenic-center-in-isoindolinones-bearing-three-aryl-groups-abstract/174005/",4,{"url":51,"name":14,"@type":54,"author":55,"headline":14,"publisher":57,"fileFormat":60,"inLanguage":23,"description":15,"dateModified":61,"datePublished":61,"encodingFormat":60,"isAccessibleForFree":62,"interactionStatistic":63},"DigitalDocument",{"name":9,"@type":56},"Person",{"url":41,"name":58,"@type":59},"DocShare","Organization","application/vnd.openxmlformats-officedocument.wordprocessingml.document","2026-09-02",true,{"@type":64,"interactionType":65,"userInteractionCount":4},"InteractionCounter",{"@type":66},"ViewAction",{"@type":68,"mainEntity":69},"FAQPage",[70,76,80],{"name":71,"@type":72,"acceptedAnswer":73},"What is the key transformation described in the document?","Question",{"text":74,"@type":75},"An efficient enantioselective formal Betti reaction forms isoindolinone derivatives via reactions between phenols and diaryl ketimines generated in situ from isoindolinone alcohols.","Answer",{"name":77,"@type":72,"acceptedAnswer":78},"Which catalyst class is used to achieve enantioselectivity?",{"text":79,"@type":75},"A chiral phosphoric acid catalyzes the reaction, enabling high enantioselectivity and regioselectivity across a range of substrates.",{"name":81,"@type":72,"acceptedAnswer":82},"How do catalyst substituents affect the enantiomeric outcome?",{"text":83,"@type":75},"Changing substituents on the chiral phosphoric acid impacts enantioselectivity; some bulkier or differently positioned groups reduce enantiomeric ratios, while certain aromatic substitutions improve enantioselective purity.","https://schema.org",{"og:url":51,"og:type":86,"og:title":14,"og:site_name":58,"og:description":15},"article",{"robots":88,"canonical":51},"index,follow",{"doc_id":7,"site_id":24},{"code":4,"msg":5,"data":91},[92,97,102,107,112,117,122,127,132],{"id":93,"doc_module":11,"doc_module_name":46,"category_name":94,"show_sort_weight":95,"slug":96},11,"Presentations",90,"presentations",{"id":98,"doc_module":11,"doc_module_name":46,"category_name":99,"show_sort_weight":100,"slug":101},12,"Resumes",80,"resumes",{"id":103,"doc_module":11,"doc_module_name":46,"category_name":104,"show_sort_weight":105,"slug":106},14,"Invoices",70,"invoices",{"id":108,"doc_module":11,"doc_module_name":46,"category_name":109,"show_sort_weight":110,"slug":111},15,"Posters",60,"posters",{"id":113,"doc_module":11,"doc_module_name":46,"category_name":114,"show_sort_weight":115,"slug":116},16,"Social Media",50,"social-media",{"id":118,"doc_module":11,"doc_module_name":46,"category_name":119,"show_sort_weight":120,"slug":121},17,"Forms",40,"forms",{"id":123,"doc_module":11,"doc_module_name":46,"category_name":124,"show_sort_weight":125,"slug":126},18,"Letters",30,"letters",{"id":128,"doc_module":11,"doc_module_name":46,"category_name":129,"show_sort_weight":130,"slug":131},21,"Paper Templates",5,"papers-templates",{"id":12,"doc_module":11,"doc_module_name":46,"category_name":13,"show_sort_weight":4,"slug":133},"general-158"]