20.500.12556/RUL-121035 Dvojna vloga paladijevega katalizatorja v alkiniliranju aril halidov Dual role of palladium catalyst in alkynylation of aryl halides V doktorskem delu smo predstavili nova spoznanja, poti in metode Sonogashirovega alkiniliranja (hetero)aril bromidov in kloridov pri sobni temperaturi, brez bakra kot ko-katalizatorja. S sočasno uporabo dveh različnih paladijevih predkatalizatorjev, pri čemer je eden omogočal oksidativno adicijo (hetero)aril bromidov, drugi pa aktivacijo terminalnih acetilenov, smo razvili katalitski sistem, ki temelji na Pd–Pd transmetalaciji. Z omenjenim katalitskim sistemom smo uspešno sintetizirali serijo alkil, aril in heteroaril substituiranih alkinov pri sobni temperaturi brez uporabe bakra. Neodvisno smo pripravili dva ključna intermediata, oksidativni adukt in paladijev acetilid, ter z njima ponazorili korak transmetalacije, ki je vodila do nastanka želenih produktov. S tandemom Pd–Pd smo prav tako uspešno pripravili sintezni intermediat zdravilne učinkovine (API) in izvedli reakcijo na več-gramski skali, pri čemer smo uporabili zgolj 0.125 mol % celokupnega paladija. Poleg tega smo razvili še dva katalitska sistema za alkiniliranje (hetero)aril bromidov in kloridov pri sobni temperaturi. Sistem (PhCN)2PdCl2/JohnPhos nam je omogočal pretvorbe aktiviranih in deaktiviranih (hetero)aril bromidov ob uporabi zgolj stehiometrijske količine aril in alkil acetilenov pri sobni temperaturi. Sistem je bil tudi uporabljen na več-gramski skali, kjer smo za dosego želenega rezultata potrebovali zgolj 0.0125 mol % paladija. S sistemom PdCl2/XPhos pa smo uspešno pretvorili slabše reaktivne aril kloride v pripadajoče alkinilirane produkte ter s tem predstavili do sedaj prvi katalitski sistem zmožen alkiniliranja aril kloridov brez bakra pri sobni temperaturi oziroma pri temperaturi 60°C. This thesis is aimed to introduce novel insights, systems and methods in Sonogashira alkynylation of (hetero)aryl bromides and chlorides at room temperature in the absence of copper co-catalyst. By simultaneous introduction of two different palladium pre-catalysts, one tuned to promote oxidative addition of (hetero)aryl bromides, and the other tuned to activate terminal acetylenes, novel catalytic system was developed based on effective Pd–Pd transmetallation. Herein described Pd–Pd system was used in the synthesis of alkyl, aryl and heteroaryl substituted alkynes at room temperature without any copper additives. Two key intermediates, oxidative addition adduct and palladium acetylide, were prepared independently, and used in the transmetallation reaction to produce desired cross-coupled products. Pd–Pd tandem was also used in the preparation of synthetic intermediate of active pharmaceutical ingredient (API),and in a multi-gram scale synthesis with as low as 0.125 mol % of total palladium loading. In addition, two other catalytic systems for alkynylation of (hetero)aryl halides at room temperature have been developed. The system (PhCN)2PdCl2/JohnPhos was able to cross-couple activated and deactivated (hetero)aryl bromides with only stoichiometric amounts of aryl and alkyl acetylenes at room temperature. Furthermore, it was also used on a multi-gram scale synthesis where only 0.0125 mol % of palladium was needed to achieve the desired results. The system PdCl2/XPhos enabled couplings of less reactive aryl chlorides and alkynes into desired alkynylation products and represents the first catalytic system capable of alkynylation of aryl chlorides with no copper additives at room temperature or at 60 °C. paladij reakcije spajanja Sonogashira transmetalacija mehanizem palladium cross-coupling Sonogashira transmetallation mechanism true false false Slovenski jezik Angleški jezik Doktorsko delo/naloga 2020-09-29 10:05:01 2020-09-29 10:05:01 2022-09-01 04:01:15 0000-00-00 00:00:00 2020 0 0 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 5702 32160515 Martek_Bruno_aleksander_-_Dvojna_vloga_paladijevega_katalizatorja_v_alkiniliranju_aril_halidov.pdf Martek_Bruno_aleksander_-_Dvojna_vloga_paladijevega_katalizatorja_v_alkiniliranju_aril_halidov.pdf 1 D3AE11ED23D9D4434B08D5E4A7860949 12de882ae55c571ffed2de50ca36fe5f127df35693058f6ce30ef7332bfcb29a 35760c40-a1ba-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=135883 Fakulteta za kemijo in kemijsko tehnologijo 0 0 0