Transmetalacija kot ključni korak s paladijem kataliziranega spajanja med aril halidi in terminalnimi acetileni

Ivančič, Anže (author), Gazvoda, Martin (mentor)

S paladijem katalizirane reakcije spajanja so eno ključnih orodij sintezne organske kemije. Poznavanje reakcijskega mehanizma je ključno tako za optimizacijo že odkritih kot tudi za razvoj novih kataliziranih reakcij. V sklopu raziskovalnega dela smo raziskovali mehanizem s paladijem kataliziranega spajanja aril halidov in terminalnih alkinov, ki kljub številnim poskusom razlage še vedno ni dokončno potrjen. Problem smo poskusili rešiti z novim pristopom k analizi opisanega mehanizma in sicer z razdelitvijo predpostavljenega mehanizma na posamezne stopnje, ki smo jih nato ločeno analizirali z jedrsko magnetno resonanco (NMR). Da bi študij posameznih korakov katalitskega procesa lahko izvedli, smo morali najprej pripraviti ključne intermediate predpostavljenega reakcijskega mehanizma – paladijeve alkinil halide, paladijeve bisalkinile in paladijeve aril halide. Čeprav je bila sinteza slednjih že opisana, pa so paladijevi alkinil halidi oz. bisalkinili manj poznani. Prve smo pripravili iz izhodnih terminalnih alkinov v dveh, druge pa v treh sinteznih korakih. Za sintezo simetričnih paladijevih bisalkinilov smo razvili tudi sintezno metodo, s katero je te koordinacijske zvrsti mogoče pripraviti v enem sinteznem koraku. Pripravljene paladijeve organokovinske zvrsti smo uporabili za študij vpliva substituentov na posameznem intermediatu na hitrost transmetalacije, ki je ključen korak predpostavljenega reakcijskega mehanizma. Z analizo reakcijske kinetike stehiometričnih reakcij med paladijevimi organokovinskimi zvrstmi smo odkrili, da ima halidni anion v paladijevem aril halidu največji vpliv na hitrost transmetalacije, kar smo uspešno uporabili za pospeševanje katalitskih reakcij med fenilacetilenom in 4-jodotoluenom, kataliziranih s preprostim paladijevim predkatalizatorjem (Pd(PPh$_3$)$_2$I$_2$). Ovrednotili smo tudi vpliv ostalih snovi, denimo liganda (trifenilfosfin) ali organske baze (pirolidin), na posamezne korake predpostavljenega reakcijskega mehanizma. Nova spoznanja nam omogočajo boljši vpogled v reakcije terminalnih alkinov in aril jodidov, kataliziranih s paladijem. Opisano metodo izolacije ključnih intermediatov in študija transmetalacij med njimi smo uporabili za napoved uspešnosti nekaterih drugih, še neopisanih katalitskih reakcij, z njihovo uspešno izvedbo pa potrdili splošno uporabnost metode.

• Language: Slovenian
• Keywords: paladij, mehanizem, kooperativna kataliza, paladijevi bisalkinili, kinetika
• Work type: Doctoral dissertation
• Typology: 2.08 - Doctoral Dissertation
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2025
• PID: 20.500.12556/RUL-166422
• COBISS.SI-ID: 225470979
• Publication date in RUL: 10.01.2025

Secondary language

• Language: English
• Title: Transmetallation as a key step of palladium catalysed cross-coupling between aryl halides and terminal acetylenes

Abstract

Palladium-catalysed cross-coupling reactions are one of the most powerful tools in synthetic organic chemistry. The understanding of reaction mechanisms is vital to the optimization of known transformations and the development of new palladium-catalysed reactions. In this research work, we studied the mechanism of palladium-catalyzed coupling of aryl halides and terminal alkynes, which has still not been definitively confirmed despite numerous efforts to solve it. Our goal was to uncover the proposed reaction mechanism by dividing it into individual steps and analysing them, mainly by using nuclear magnetic resonance (NMR) spectroscopy. In order to gain insight into each individual step of the mechanism, key intermediates – palladium alkynyl halides, palladium bisalkynyls and palladium aryl halides – had to be prepared. The synthesis of the latter was already reported, however, palladium alkynyl halides and bisalkynyls are less known. The former were prepared from corresponding terminal alkynes in two synthetic steps, and the latter were prepared in three. We have also developed a new synthetic method for preparation of symmetrical palladium bisalkynyls in one synthetic step. The prepared palladium organometallic compounds were used to investigate the effect of substituents on the rate of transmetallation, the crucial step of the proposed reaction mechanism. The analysis of the reaction kinetics revealed that the halide in palladium aryl halide has the greatest influence on the transmetallation rate. This discovery was used to accelerate the catalytic reaction between phenylacetylene and 4-iodotoluene, catalysed by a simple palladium precatalyst (Pd(PPh$_3$)$_2$I$_2$). We have also evaluated the effect of other substances, i.e. ligand (triphenylphosphine) and organic base (pyrrolidine), on the separate steps of the proposed reaction mechanism. These new insights allowed us to better understand the palladium-catalysed reactions of terminal alkynes and aryl iodides. The described method was used to predict and confirm the success of new catalytic reactions.

• Keywords: palladium, mechanism, cooperative catalysis, palladium bisalkynyls, kinetics