Title Enantioselektivna sinteza α-kvaternih (triaril)metanamina katalizirana kiralnim brØnstedovim kiselinama Title (english) Chiral brØnsted acid-catalyzed enentioselective synthesis of α-quaternary (triaryl)methanamines Author Danijel Glavač Mentor Matija Gredičak (mentor)Committee member Karlo Wittine (predsjednik povjerenstva)Committee member Srećko Kirin (član povjerenstva)Committee member Nela Malatesti (član povjerenstva)Committee member Matija Gredičak (član povjerenstva)Granter University of Rijeka Defense date and country 2019-09-20, Croatia Scientific / art field, BIOTECHNICAL SCIENCES Universal decimal classificationUDC ) 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
... More 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. Less 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,
... More 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. Less Keywords
α-kvaterni (triaril)metanamini
kiralne Brønstedove kiseline
asimetrična organokataliza
3-hidroksiizoindolinoni
N-(acil)ketimini
Keywords (english)
α-quaternary (triaryl)methanamines
chiral Brønsted acid
asymmetric organocatalysis
3-hydroxyisoindolinones
N-(acyl) ketimine
Language croatian URN:NBN urn:nbn:hr:193:260749 Promotion 2021 Study programme Title: Medicinal chemistry Type of resource Text File origin Born digital Access conditions Access restricted to students and staff of home institution Terms of use Created on 2021-04-26 09:01:29
