Stereoselektivna arilacija diaril-ketimina katalizirana kiralnim Brønstedovim kiselinama

master's thesis

• Title (english): Stereoselective arylation of diaryl-ketimines catalyzed by chiral Brønsted acids
• Author: Gabrijel Zubčić
• Mentor: Irena Škorić (mentor)
• Mentor: Matija Gredičak (komentor)
• Committee member: Irena Škorić (predsjednik povjerenstva)
• Committee member: Lidija Furač (član povjerenstva)
• Committee member: Matija Gredičak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Chemical Engineering and Technology; Zagreb
• Defense date and country: 2020-09-21, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U sklopu ovog rada pripravljeni su α-(diaril) izoindolinonski alkoholi (1-5) koji su poslužili kao polazni supstrati za pripravu racemičnih (6-12) i kiralnih (13-19) α-kvaternih triarilmetanamina primjenom formalne Bettijeve reakcije. Provedena je priprava 3-supstituiranih-3-hidroksiizoindolinona upotrebom organometalnih reagensa. Fenilni supstituenti s elektron-donirajućim skupinama (1-2) reagirali su s ftalimidom u Grignardovoj reakciji, dok su elektron-odvlačeće skupine (3-4) zahtijevale litij-brom izmjenu. Izoindolinonski alkohol s tiofenskim supstituentom (5) je sintetiziran strategijom izravne litijacije. Ostali upotrijebljeni alkoholi su već prethodno sintetizirani u Laboratoriju i njihova sinteza nije dio ovog rada. Uslijedila je provedba racemične formalne Bettijeve reakcije, koja uključuje adiciju 2,6-dimetilfenola na in situ generirani α-(diaril)-N-(acil)ketimin iz 3-aril-3-hidroksiizoindolinona (1-5) uz para-toluensulfonsku kiselinu kao katalizator. Dobiveni α-kvaterni triarilmetanamini (6-12) izolirani su u slabim do izvrsnim prinosima. U stereoselektivnoj verziji reakcije kao izvor kiralnosti koristila se kiralna fosforna kiselina (CPA) s binaftilnom okosnicom. Nastali Bettijevi produkti (13-19) izolirani su u slabim do izvrsnim prinosima i umjerenim do visokim vrijednostima enantioselektivnosti.

Abstract (english)

Within this work α-(diaryl) isoindolinone alcohols (1-5) have been prepared and used as inital supstrates for the preparation of racemic (6-12) and chiral (13-19) α-quaternary triarylmethanamines through formal Betti reaction. Preparation of 3-substituted-3-hydroxyisoindolinones was carried out by using organometallic reagents. Phenyl substituents with electron-donating groups (1-2) reacted with phthalimide via the Grignard reaction, while the electron-withdrawing groups required bromine-lithium exchange (3-4). Isoindolinone alcohol with a thiophene substituent was synthesized by direct lithiation strategy (5). Other alcohols where synthesised beforehand in the Lab and their synthesis was not part of this work. In a racemic formal Betti reaction, the addition of 2,6-dimethylphenole to in situ generated α-(diaryl)-N-(acyl)ketimines from 3-aryl-3-hydroxyisoindolinones (1-5) was performed by utilizing para-toluenesulfonic acid as catalyst. Obtained α-quaternary triarylmethanamines (6-12) were isolated in good to excellent yields. In the stereoselective version of the reaction, chiral phosphoric acid (CPA) with binaphthyl framework was used. Obtained Betti products (13-19) were isolated in good to excellent yields, and with moderate to excellent enantioselectivity.

• Keywords: α-kvaterni triarilmetanamini; 3-supstituirani-3-hidroksiizoindolinoni; para-toluensulfonska kiselina; kiralna fosforna kiselina; α-(diaril)-N-(acil)ketimin
• Keywords (english): α-quaternary triarylmethane amines; 3-substituted-3-hydroxyisoindolinones; para-toluenesulfonic acid; chiral phosphoric acid; α-(diaryl)-N-(acyl)ketimines
• Language: croatian
• URN:NBN: urn:nbn:hr:149:113171
• Study programme: Title: Applied Chemistry - Graduate study; specializations in: Environmental chemistry and green technologies, Advanced materials and technologies, Applied organic chemistry; Course: Applied organic chemistry; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra primijenjene kemije (magistar/magistra primijenjene kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-04-21 13:04:12