20.500.12556/RUL-125868 Mezoionski paladijev kompleks kot katalizator za tvorbo vezi C-N in C-F C-N and C-F bond formation catalyzed by a mesoionic palladium complex S paladijem katalizirane reakcije predstavljajo pomembno področje v organski kemiji. V naši raziskovalni skupini je bil razvit mezoionski paladijev NHC kompleks [Pd(Py-tzNHC)2]2+ 2(BF4–), ki je bil predhodno uspešno uporabljen za katalizo reakcij spajanja, za tvorbo nove vezi ogljik-ogljik (C–C). Naš namen je bil, da raziščemo uporabo omenjenega Pd kompleksa za tvorbo vezi ogljik-heteroatom, natančneje, za tvorbo vezi ogljik-dušik (C–N) in ogljik-fluor (C–F). V predloženem delu smo raziskovali dve reakciji in sicer s paladijem katalizirano intermolekularno hidroaminiranje, pri čemer pride do tvorbe nove vezi C–N in s paladijem katalizirano elektrofilno aromatsko fluoriranje, kjer pride do tvorbe vezi C–F. Reakcija s paladijem kataliziranega hidroaminiranja je precej slabo raziskana. Znanih je le nekaj primerov uporabe paladijevih NHC kompleksov za katalizo intermolekularnega hidroaminiranja terminalnih acetilenov s primarnimi anilini. Pri tem so bile v večini primerov reakcije izvedene pod ostrimi reakcijskimi pogoji. Poleg tega do sedaj še ni bil potrjen noben od predlaganih mehanističnih predlogov reakcije. S pomočjo eksperimentalnih in teoretičnih metod smo dobili podroben vpogled v mehanizem reakcije intermolekularnega hidroaminiranja kataliziranega s paladijevim [Pd(Py-tzNHC)2]2+ 2(BF4–)kompleksom. Pokazali smo, da ligand kompleksa, poleg stabilizacijske in aktivacijske vloge, prevzame še vlogo interne baze. Natančneje, struktura kompleksa omogoča disociacijo piridinskega krila, pri tem se sprosti piridinski substituent. Nekoordiniran piridin, v bližini paladijevega centra, lahko prevzame vlogo interne baze in s tem zmožnost prenosa protona. Tako smo pokazali edinstveno vlogo liganda pri katalizi reakcije. Vpogled v mehanizem reakcije nam je omogočil načrtovanje optimalnih reakcijskih pogojev. Uspešno smo razvili sintezni postopek za s paladijem katalizirano intermolekularno hidroaminiranje terminalnih acetilenov s primarnimi anilini, ki izpolnjuje zahteve glede dostopnosti izhodnih reagentov, atomske ekonomičnosti, selektivnosti in same izvedbe sinteze. Reakcija poteka pri sobni temperaturi v odsotnosti kakršnegakoli aditiva in že pri nizki količini paladijevega katalizatorja (1 mol%) ter vodi do iminskih produktov z visokimi izkoristki. Fluorirane spojine predstavljajo pomembne učinkovine v farmacevtski in agrokemijski industriji. Z uvedbo fluorovega atoma lahko modificiramo hidrofobnost molekule, preprečimo morebitne oksidacije, itd. zaradi tega je v zadnjem času veliko truda usmerjenega v razvoj blagih sinteznih metod za selektivno uvedbo fluorovega atoma. Nedavno je bila objavljena metoda za s paladijem katalizirano elektrofilno aromatsko fluoriranje, kar je edinstven primer tovrstne reakcije. Ugotovili smo, da dodatna koordinacija [Pd(Py-tzNHC)2]2+ 2(BF4–) s fenantrolinom, s čimer se popolnoma zasede kvadratno planarna koordinacijska sfera paladija, pri tem se tvori [Pd(Py-tzNHC)2(Phen)]2+ 2(BF4–), omogoči reakcijo paladijevega kompleksa z elektrofilnim fluorirnim reagentom. Na ta način se tvori reaktiven paladijev(IV)-fluoro kompleks, ki lahko fluorira elektronsko revne aromatske sisteme. Po optimizaciji reakcijskih pogojev smo reakcijo prikazali narazličnih aromatskih spojinah. Naloga zajema razvoj novih metod za tvorbo vezi ogljik-heteroatom, natančneje vezi ogljik-dušik in ogljik-fluor. Razvoj postopkov je bil usmerjen tako, da omogoča pripravo do sedaj nedostopnih organskih spojin in hkrati izpolnjuje zahteve glede dostopnosti materialov, atomske ekonomičnosti, selektivnosti in same izvedbe sinteze. S tem smo dosegli izboljšanje sinteznih metod v primerjavi z literaturno znanimi. Hkrati smo z eksperimentalnimi študijami raziskali mehanizme reakcij, kar je imelo ključni pomen pri racionalnem načrtovanju in optimizaciji reakcijskih pogojev ter hkrati odprlo nove poti za nadljnje raziskovalno delo. Palladium catalyzed reactions represent an important field in organic chemistry. Our research group have previously reported a mesoionic palladium NHC complex [Pd(Py-tzNHC)2]2+ 2(BF4–) that has been employed in cross-coupling catalysis for C–C bond formation. Our purpose was to extend the scope of catalysis of palladium complex to the formation of carbon-heteroatom bonds, specifically, for the formation of carbon-nitrogen (C–N) and carbon-fluorine (C–F) bonds. In the present work, we investigated two reactions, namely palladium-catalyzed intermolecular hydroamination, which results in the formation of a new C–N bond, and palladium-catalyzed electrophilic aromatic fluorination, where C–F bond formation occurs. The area of palladium catalyzed hydroamination has not yet been investigated in detail. There are only few reports on the use of palladium NHC complexes for catalytic intermolecular hydroamination of terminal acetylenes with primary anilines. In most cases, the reactions were carried out under harsh reaction conditions, i.e. elevated temperatures and additions of acid or base. In addition, none of the mechanistic proposals for described reaction has been confirmed so far. By employing different experimental and theoretical methods, we got an insight into the reaction mechanism of the intermolecular hydroamination reaction catalyzed by the palladium [Pd(Py-tzNHC)2]2+2(BF4–) complex. We have shown that in addition to the stabilizing and activating role, pyridine wingtip of the Py-tzNHC ligand can also take on the role of an internal base. Namely,dissociation of pyridine wingtip from palladium allows substrate an access to the metal center, besides that uncoordinated pyridine can take the role of an internal base and is able of intermolecular proton transfer during catalysis. This demonstrated the unique role of the ligand in the catalysis for this type of reaction. Insight into the reaction mechanism allowed us to optimize reaction conditions. We have developed a synthetic procedure for palladium-catalyzed intermolecular hydroamination of terminal acetylenes with primary anilines, which meets the requirements regarding the availability of starting reagents, atomic economy, selectivity and is simple to perform. The reaction takes place at room temperature in the absence of any additive and with a low loading of palladium catalyst (1 mol%), producing imine products in high yields. Fluorinated compounds play important role in pharmaceutical and agrochemical industry. By introducing fluorine atom, we can alter the hydrophobicity of the molecule, prevent possible oxidation, etc. Because of that a lot of effort has recently been focused on the development of synthetic methodologies for introduction of fluorine atom under mild reaction conditions. Recently, a method for palladium-catalyzed electrophilic aromatic fluorination has been reported, which is a unique example of this type of reaction. We found that additional coordination of [Pd(Py-tzNHC)2]2+2(BF4–) with phenanthroline, by which the square-planar coordination sphere of palladium is completely occupied and [Pd(Py-tzNHC)2(Phen)]2+2(BF4–)is formed, allows the palladium complex to react with the electrophilic fluorinating reagent. In this way, a reactive palladium (IV)-fluoro complex is formed that can fluorinate electronically poor aromatic systems. After optimization of the reaction conditions, the reaction was demonstrated on various aromatic compounds. The doctoral thesis involves the development of new methods for the formation of carbon-heteroatom bonds, more specifically carbon-nitrogen and carbon-fluorine bonds. The development of processes was directed in such a way as to enable the preparation of hitherto inaccessible organic compounds and at the same time meet the requirements regarding the availability of materials, atomic economy, selectivity and the implementation of the synthesis itself. In this way, we achieved an improvement in synthetic methods compared to those known in the literature. At the same time, we investigated the mechanisms of reactions with experimental studies, which was of key importance in the rational planning and optimization of reaction conditions, and opened new way at the research work. paladij kataliza vez C–N vez C–F hidroaminiranje fluoriranje palladium catalysis C–Nbond C–Fbond hydroamination fluorination true false false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2021-04-08 09:15:00 2021-04-08 09:15:00 2022-09-05 03:53:03 0000-00-00 00:00:00 2021 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 7261 60564227 Mihelac_Mateja_-_Mezoionski_paladijev_kompleks_kot_katalizator_za_tvorbo_vezi_C-N_in_C-F.pdf Mihelac_Mateja_-_Mezoionski_paladijev_kompleks_kot_katalizator_za_tvorbo_vezi_C-N_in_C-F.pdf 1 586D3E8E5FA220671B7C7069CDCE5E5C a7f815359b7e73767340625016b963cdf5e7b2d87912635f7f1de723ad0fdad2 cf59b317-a1bb-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=141733 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0