| Keywords [eng] |
Fluorinimas, fluorinimo katalizatoriai, paladis, paladžio katalizė, kryžminis jungimas, C-F ryšys, fosfininiai ligandai, organofosforo chemija. |
| Abstract [eng] |
Pharmaceutical sciences have focused on the unique properties of fluorinated compounds, that tend to exhibit more favorable biological activities in comparison to their non-fluorinated counterparts. However, catalytic approaches for C-F bond formation are lacking. Palladium catalysis has been established and well-studied for the C-C, C-O, C-N, C-S, C-P cross-coupling reactions. On the other hand, palladium catalyzed fluorination reactions are a relatively new field in organic chemistry. The work described in this thesis focuses on the design and synthesis of phosphine ligands and their steric and electronic influences on fluorination reactions. Divergent approach for the synthesis of AlPhos ligand and its new analogues with differing phosphine moieties was developed and adapted. It allowed for multi-gram-scale synthesis of phosphine ligands and therefore increased their diversity. A new synthetic strategy for cyclic and bicyclic phosphines based on umpolung (C+/P-) method was conceptualized and is currently under development. Telomerisation issue reported in literature was solved by generating phosphine nucleophile in situ using P(TMS)3. Cyclic “caged” phosphine ligand architecture was assessed by computational and empirical methods. The results showed that both sterics and electronics affect the catalytical cycle, however, their influences have to be tuned for the optimal catalytic activity. Potential lead ligand candidate, based on 1,3,5,7-tetramethyl-2,4,6-trioxa-8-phosphaadamantane framework, was identified for further study. Fluorination reaction was optimized to work with less fastidious palladium sources and without the need of a glovebox for more consistent screening of the ligands. |
