Optimized Immobilization Strategy for Dirhodium(II) Carboxylate Catalysts for C−H Functionalization and Their Implementation in a Packed Bed Flow Reactor

Abstract

Herein we demonstrate ap acked bed flow reactor capable of achieving highly regio-and stereoselective CÀH functionalization reactions using an ewly developed Rh 2 (S-2-Cl-5-CF 3 TPCP) 4 catalyst. To optimize the immobilized dirhodium catalyst employed in the flowr eactor,w es ystematically study both (i)t he effects of ligand immobilization position, demonstrating the critical factor that the catalyst-support attachment location can have on the catalyst performance, and (ii)s ilica support mesopore length, demonstrating that decreasing diffusional limitations leads to increased accessibility of the active site and higher catalyst turnover frequency. We employt he immobilized dirhodium catalyst in as imple packed bed flow reactor achieving comparable yields and levels of enantioselectivity to the homogeneous catalyst employed in batch and maintain this performance over ten catalyst recycles.

Designing Sites in Heterogeneous Catalysis: Are We Reaching Selectivities Competitive With Those of Homogeneous Catalysts?

“… In another example, with a tethered rather than grafted catalyst, Rh 2 (trifluoro­acetate) 4 was complexated to SBA-15 derivatized with amino (APTES) groups either alone or in combination with carboxylic ligands; the latter was clearly superior for the promotion of the cyclopropanation of styrene with ethyl diazoacetate . More subtle but also important is the position at which the ligand bonds to both the linker used for tethering and the immobilized metal ion-ligand: for instance, it has been possible to tune the regio- and stereo-selective of C–H functionalization reactions using a tethered chiral Rh 2 (S-ortho-Cl-(1,2,2-triarylcyclo­propane carboxylate) 4 catalyst by varying the ligand immobilization position . A similar effect related to the point of tethering within the molecular functionalities can be seen with non-metallic organic groups, as illustrated in the examples shown in Figures and . , It is interesting that in those studies it was found that the enantioselectivity of the thiol addition to 2-cyclohexen-1-one decreases not only upon tethering of the cinchona alkaloid catalyst to a silica surface but also if physical mixtures of the homogeneous catalyst with pure silica are used; this is a case where the acid sites of the support independently promote undesirable side reactions (the non-enantioselective coupling of the reactants) .…”