Sinteza kiralnih tercijarnih alkohola Grignardovom reakcijom

master's thesis

• Title (english): Synthesis of chiral tertiary alcohols using Grignard reaction
• Author: Jerko Meštrović
• Mentor: Nikola Cindro (mentor)
• Committee member: Nikola Cindro (predsjednik povjerenstva)
• Committee member: Ivica Đilović (član povjerenstva)
• Committee member: Nikola Bregović (član povjerenstva)
• Committee member: Josip Požar (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2022-03-18, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

U okviru ovog rada istražena je adicija Grignardovih reagensa na lakton izveden iz D-riboze s ciljem
dobivanja kiralnih tercijarnih alkohola. Iako je uvriježeno kako dva ekvivalenta Grignardova reagensa
u reakciji s esterom daju tercijarni alkohol s dva ista supstituenta, u okviru ovog rada ispitana je
mogućnost uzastopnog dodavanja dva različita Grignardova reagensa unutar iste reakcije. S tim ciljem
provedena je sinteza 5-deoksi-2,3-izopropiliden-D-ribonolaktona kroz nekoliko koraka, te je navedeni
spoj korišten kao supstrat za generiranje kiralnih tercijarnih alkohola. Također provedena je i sinteza
dva funkcionalizirana alkil-bromida za pripravu Grignardovih reagensa, dok su drugi bili komercijalno
dostupni. Dobiveni ribonolakton preveden je u različite kiralne alkohole. U prvom stupnju reakcije
adiran je alilmagnezijev bromid, dok je u drugom stupnju dodan drugi Grignardov reagens. Na taj način
generirana su 4 kiralna tercijarna alkohola. Produkti su izolirani i okarakterizirani spektroskopskim
metodama.
Dobiveni rezultati poslužiti će za daljnji razvoj navedene metodologije uvođenja kiralnih
tercijarnih alkohola u zahtjevnije molekule što će potencijalno omogućiti efikasniju i jednostavniju
pripravu novih djelatnih tvari.

Abstract (english)

In this thesis the addition of Grignard reagent on lactones derived from D-ribose was examined with the
intention of generating new chiral tertiary alcohols. Although it is known that the addition of two equivalents
of a Grignard reagent to an ester will form a tertiary alcohol with two identical substituents, in this thesis the
possibility of a sequential addition of two different Grignard reagents in the same reaction was researched.
To that end, 5-deoxy-2,3-isopropylidene-D-ribonolactone was synthesized in four steps and used as a
substrate for generating chiral tertiary alcohols. Furthermore, synthesis of two functionalized alkyl-bromide
derivatives was performed for the preparation of Grignard reagents with others being commercially available.
The synthesized ribonolactone was converted into different chiral tertiary alcohols. In the first step of the
reaction, allylmagnesium bromide was added and then in the second step the other Grignard reagent was
added. With this approach, four chiral tertiary alcohols were generated. The products were isolated and
characterized with spectroscopic methods.
The obtained results will be of great use in the further development of this methodology with the
purpose of introduction of a new chiral tertiary alcohol group to complex molecules. With this in mind, it is
a possibility that this method will provide a more efficient and simpler procedure in the synthesis of new
active pharmaceutical ingredients.

• Keywords: alilmagnezijev bromid; Grignardova reakcija; Grignardov reagens; kiralan; lakton; stereoselektivna sinteza; tercijarni alkohol
• Keywords (english): allylmagnesium bromide; chiral; Grignard reaction; Grignard reagens; lactone; stereoselective synthesis; tertiary alcohol
• Language: croatian
• URN:NBN: urn:nbn:hr:217:947565
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-04-20 09:18:59