prikaz prve stranice dokumenta Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama
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doctoral thesis
Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama
2019. urn:nbn:hr:193:260749
Glavač, Danijel
University of Rijeka
Faculty of Biotechnology and Drug Development

Cite this document

Glavač, D. (2019). Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama (Doctoral thesis). Rijeka: University of Rijeka. Retrieved from https://urn.nsk.hr/urn:nbn:hr:193:260749

Glavač, Danijel. "Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama." Doctoral thesis, University of Rijeka, 2019. https://urn.nsk.hr/urn:nbn:hr:193:260749

Glavač, Danijel. "Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama." Doctoral thesis, University of Rijeka, 2019. https://urn.nsk.hr/urn:nbn:hr:193:260749

Glavač, D. (2019). 'Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama', Doctoral thesis, University of Rijeka, accessed 17 November 2024, https://urn.nsk.hr/urn:nbn:hr:193:260749

Glavač D. Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama [Doctoral thesis]. Rijeka: University of Rijeka; 2019 [cited 2024 November 17] Available at: https://urn.nsk.hr/urn:nbn:hr:193:260749

D. Glavač, "Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama", Doctoral thesis, University of Rijeka, Rijeka, 2019. Available at: https://urn.nsk.hr/urn:nbn:hr:193:260749

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Metadata
TitleEnantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama
Title (english)Chiral brØnsted acid-catalyzed enentioselective synthesis of α-quaternary (triaryl)methanamines
AuthorDanijel Glavač
MentorMatija Gredičak (mentor)
Committee memberKarlo Wittine (predsjednik povjerenstva)
Committee memberSrećko Kirin (član povjerenstva)
Committee memberNela Malatesti (član povjerenstva)
Committee memberMatija Gredičak (član povjerenstva)
GranterUniversity of Rijeka
(Faculty of Biotechnology and Drug Development)
Rijeka
Defense date and country2019-09-20, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Universal decimal classification
(UDC)		577 - Biochemistry. Molecular biology. Biophysics
Abstract
U sklopu ove disertacije pripravljena je serija α-(diaril) izoindolinonskih alkohola 1–24 koja je poslužila kao polazni supstrat za razvoj metodologije priprave kiralnih α-(3-indolil)(diaril)metanamina 26–60 i α-(triaril)metanamina 61–91. Provedeno je detaljno ispitivanje priprave 3-supstituiranih 3-hidroksiizoindolinona upotrebom organometalnih reagensa. Fenilni supstituenti s elektron-donirajućim skupinama reagirali su s ftalimidom u Grignardovoj reakciji, dok su elektron-odvlačeće skupine i heteroaromatske jezgre zahtijevale litij-brom izmjenu ili strategiju izravne litijacije. Protokoli su tolerantni prema različitim funkcionalnim skupinama, a širok raspon 3-hidroksiizindolinona 1–24 dobiven je u dobrim i izvrsnim prinosima. Razrađena je studija razvoja aza-Friedel-Craftsove asimetrične adicije indola na cikličke α-(diaril) supstituirane N-(acil)ketimine, generiranih in situ iz 3-aril-3-hidroksiizoindolinona. Enantioselektivna transformacija katalizirana kiralnim Brønstedovim kiselinama SPINOL-ne okosnice tolerira širok spektar različito supstituiranih indola i izoindolinonskih alkohola. Reakcijom su dobiveni α-kvaterni (3-indolil)(diaril)metanamini 26–60 u odličnim prinosima i razinama enantioselektivnosti (do 98 % prinosa, >99:1 e.r.). Izvor stereokemijske indukcije potkrijepljen je računalnim (DFT) i eksperimentalnim metodama. Opisano je i istraživanje razvoja asimetrične Bettijeve reakcije fenola s α-(diaril) izoindolinonskim alkoholima 1–24 katalizirane kiralnim fosfornim kiselinama BINOL-ne strukture u svrhu dobivanja α-kvaternog (triaril) stereogenog centra. Reakcija je tolerantna na širok raspon supstituiranih 3-arilnih prstena izoindolinona 1–24, te na različite supstituente u para-položaju fenolnog nukleofila. Dobiveni α-(triaril)metanamini 61–91 izolirani su u dobrim do izvrsnim prinosima i umjerenim razinama enantioselektivnosti.
Abstract (english)
Within this Thesis, a series of α-(diaryl) isoindolinone alcohols 1–24 were prepared which served as the starting materials for the development of a methodology for the preparation of chiral α-(3-indolyl)(diaryl) methanamines 26–60 and α-(triaryl) methanamines 61–91. A detailed investigation of the synthesis of 3–substituted 3-hydroxyisoindolinones with organometallic reagents is described. Phenyl groups with electron-donating substituents are easily introduced by employing Grignard reaction, while aryls with electron-withdrawing groups and heteroaromatic cores require lithium exchange or direct lithiation strategy. The protocols are tolerant of various functional groups, and a wide range of 3-hydroxyisoindolinones 1–24 were afforded in good to excellent yields. The study of asymmetric aza-Friedel-Crafts reaction between indoles and cyclic α-diaryl-substituted N-acyl imines, generated in situ from 3-aryl 3-hydroxyisoindolinones, is described. The enantioselective transformation proceeds smoothly with a broad range of indoles and isoindolinone alcohols using a SPINOL-derived chiral Brønsted acid catalyst to afford α-quaternary (3-indolyl)(diaryl)methanamines 26–60 in excellent yields and enantioselectivities (up to 98% yield, up to >99:1 e.r.). The origin of stereochemical induction is supported by DFT calculations and experimental data. The study of asymmetric Betti reaction between phenol derivatives and α-(diaryl) isoindolinone alcohols 1–24 catalyzed by chiral phosphoric acids for the construction of α-quaternary (triaryl) stereogenic centre is developed. The reaction is tolerant to a wide range of 3-aryl substituents on 3-hydroxyisoisoindolinones 1–24, as well as in the para-position of the phenol nucleophiles. The resulting α-(triaryl) methanamines 61–91 were isolated in good yields and moderate levels of enantioselectivity.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:193:260749
Promotion2021
Study programmeTitle: Medicinal chemistry
Study programme type: university
Study level: postgraduate
Academic / professional title: doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini (doktor/doktorica znanosti, interdisciplinarna područja znanosti, polje biotehnologija u biomedicini)
Type of resourceText
File originBorn digital
Access conditionsAccess restricted to students and staff of home institution
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Created on2021-04-26 09:01:29