Modular synthesis of hyperbranched polyglycerol supported N-heterocyclic carbene ligands for application in catalysis (2009)

In this work, a highly efficient and modular synthesis of polyglycerol supported N-heterocyclic carbene ligands for application in catalysis were developed. In the first part triazole moieties, as simple method for linking the polyglycerol polymer core with NHC ligands, were introduced. The complexation of palladium yielded stable and under aerobic conditions storeable metal complexes (dendritic catalysts 5, 8 and 12). The dendritic catalysts were compared to commercially available NHC ligands and proved to be equally active in Suzuki Miyaura cross coupling reactions using phenylboronic acid and various aryl bromides. Furthermore, the origin of negative dendritic effects for these systems could be attributed to inaccessible catalytically active sites (dendritic catalyst 5). We hypothesized that this negative dendritic effect is due to a low accessibility of the catalytic active site. Reduction of the polymer loading resulted in a more flexible structure and an enhanced accessibility of the catalytic active site (dendritic catalyst 8). By this modification it was also possible to use the sterically demanding 2 -tolyl-boronic acid with good conversions which was not possible before. As highly loaded polymers are preferable to the lower loaded ones owing to the price of the catalyst a flexible N-cyclohexyl-imidazole ligand (dendritic ligand 12) was introduced instead of the N-mesityl-imidazole of the previous tries. This strategy was so successful that besides sterically demanding boronic acids also heterobornic acids could be applied. This catalyst (dendritic catalyst 12) could be reused several times though formation of palladium black could be observed after multiple reuse. After the evaluation of the influence of the NHC ligand on the activity in transition metal catalysis, we tested the impact of the triazole moiety as well as the polymer back bone. Therefore, three monomeric ligands were synthesized (ligands 21, 23 and 24). These varied in similarity to the polyglycerol supported ligands by bearing the triazole moiety (ligand 23) and in addition a short oligomeric monomethoxypoly(ethylene glycol) backbone (ligand 24). It proved that the triazole moiety significantly enhanced the stability of the palladium carbene complex even though, after a week, precipitation of palladium black could be visually confirmed for the metal complex resulting from ligand 23\. The ligands without the “linking” unit did not form a stable metal complex (ligand 21) while the one possessing the oligomeric backbone could be stored for months without any visible decomposition (ligand 24, catalyst 27 respectively). The effect of the stability of the formed metal complexes on the activity was determined in Suzuki-Miyaura cross coupling procedures applying the most and least stable metal complexes. No significant change in activity could be observed for the tested substrates which indicates that the higher stability of the metal complex in these cases did not influence the activity of the catalysts. These studies on the influence of flexibility of the introduced ligands and triazole moiety lead to the synthesis of monomethoxypoly(ethylene glycol) substituted NHC ligands (dendritic catalyst 20) immobilized on polyglycerol. Like the previous supported catalysts (dendritic catalysts 5, 8 and 12) it proved to be stable and storable. The mPEG substituents made the ligand as well as the metal complex water soluble. We could show that for palladium mediated coupling of 4´-bromoacetophenone and phenylboronic acid water was the most suitable medium in difference to various organic solvents and high turnover number of up to 59000 could be achieved. The dendritic catalyst was tested against the best monomeric analog (catalyst 27) described earlier and it showed that both catalysts were equally active for arylboronic acids. A positive dendritic effect, however, could be observed for the application of pyridineboronic acids. While the dendritic catalyst (20) gave good conversions the monomeric catalyst completely lost its activity. The dendritic catalyst proved to be also competitive with other monomeric catalysts for this transformation as therefore up to 10 mol% of catalyst have to be applied. As the dendritic catalyst 20 was the most active and versatile synthesized catalyst it was used in a coupled process of a transition metal mediated with an enzyme mediated reaction. In preliminary studies we could prove that the dendritic catalyst is able to promote the asked for Suzuki cross coupling in good yields and that an efficient separation of the crude product from the catalyst could be performed by simple extraction with n-hexane. Furthermore, the enzyme was able to perform the benzoin coupling of 4-phenylbenzaldehyde and 63 % of the starting material could be transformed. For future experiments it could be determined that after conducting the Suzuki coupling the reaction mixture exhibits a pH of 7 which is ideal for the enzymatic reaction. In the last part a supported version of Grubbs´ catalyst was synthesized and successfuly tested in ring closing metathesis reactions (dendritic catalysts 39, 40, 43 and 44). Four different dendritic catalysts were synthesized exhibiting two different linker strategies. The already introduced triazole moiety (dendritic catalysts 39 and 40) however proved to be not suitable for metathesis applications while the ones with an alkyl linker (dendritic catalysts 43 and 44) gave good results in RCM reactions. We could demonstrate that the dendritic catalysts are especially well suited for unsubstituted terminal alekenes. Sterically hindered substrates proved to be difficult though trisubstituted cyclic alkenes could be synthesized. All of the four different kinds of catalysts could not be reused to a satisfactory extend. We can conclude that the high activities, extended stability of NHC-palladium complexes and a positive dendritic effect could be observed for polyglycerol supported metal complexes. These tokens, easy preparation and straightforward storage of these complexes make them good candidates for further testing in continuous reactions and screening processes.