Fluorous Triazole Catalysis

The first incarnation of fluorous tagging, separation, and recovery was in catalysis.  In general, ligands which are used in metal catalyzed reactions are fluorous tagged, complexed to the appropriate metal, then used as catalysts for the reaction.  The ligands and/or the metal complexes can then be recovered and reused using a variety of fluorous methods.  Fluorous biphasic catalysis using a liquid fluorous phase to immobilize the fluorous catalyst was the first used.

Prof. Oliver Reiser from the Universität Regensburg has used azabis(oxazoline) ligands with copper to catalyze a variety of transformations.  The aza-BOX ligands have been demonstrated to bind to metals more efficiently than BOX ligands making removal of the metal easier.  His group has used the nitrogen to attach the aza-BOX ligand to various supports, including a PEG based support, to immobilize the ligand to facilitate separation, recovery, and reuse.  In their most recent report they made a fluorous aza-BOX and found some interesting results.

Their initial attempt at forming a fluorous aza-BOX was a simple alkylation of the deprotonated ligand with a fluorous chloride.  A reaction which failed.  Although not mentioned in the article, this may be due to elimination of the chloride, a common side reaction with ethylene spaced fluorous halides.  A propylene spaced alkylating agent may have proved better.  In any event, they circumvented this problem by using click chemistry to attach the fluorous tag via a triazole.  In their previous experience with triazole linked aza-BOX ligands they found a significant loss of stereoselectivity in the subsequent reactions, presumably due to the ability of the triazole to also coordinate metals.

With the fluorous trizole aza-BOX ligands in hand they ran several typical copper catalyzed enantiomeric reactions, including asymmetric acylation of a diol, nitrolaldol reaction, and a Friedel-Crafts alkylation.  What they found was that the fluorous aza-Box provided similar yields and ee’s as regular aza-BOX for the first two reactions which was in direct contrast to other triazole linked supported ligands.  This is probably due to the electron withdrawing effect of the fluorous tag which lowers the coordinating ability of the triazole.  In addition, they found that simple solvent changes resulted in the precipitation of the fluorous aza-BOX ligands which could then be collected by filtration and reused up to six times with little loss of reactivity or selectivity.  Little copper or ligand leaching was claimed.  Although the yields are modest at best in the reaction below, they are comparable to other systems.

So in this instance the fluorous tag not only facilitates separation and reuse, but also attenuates the triazole reactivity enhancing the overall reaction.