Mapping Catalyst-Solvent Interplay in Competing Carboamination/Cyclopropanation Reactions

Abstract

Group 9 metals, in particular Rh^III complexes with cyclopentadienyl ligands, are competent C-H activation catalysts. Recently, a Cp*Rh^III -catalyzed reaction of alkenes with N-enoxyphthalimides showed divergent outcome based on the solvent, with carboamination favored in methanol and cyclopropanation in 2,2,2-trifluoroethanol (TFE). Here, we create selectivity and activity maps capable of unravelling the catalyst-solvent interplay on the outcome of these competing reactions by analyzing 42 cyclopentadienyl metal catalysts, Cp^X M^III (M=Co, Rh, Ir). These maps not only can be used to rationalize previously reported experimental results, but also capably predict the behavior of untested catalyst/solvent combinations as well as aid in identifying experimental protocols that simultaneously optimize both catalytic activity and selectivity (solutions in the Pareto front). In this regard, we demonstrate how and why the experimentally employed Cp*Rh^III catalyst represents an ideal choice to invoke a solvent-induced change in reactivity. Additionally, the maps reveal the degree to which even perceived minor changes in the solvent (e. g., replacing methanol with ethanol) influence the ratio of carboamination and cyclopropanation products. Overall, the selectivity and activity maps presented here provide a generalizable tool to create global pictures of anticipated reaction outcome that can be used to develop new experimental protocols spanning metal, ligand, and solvent space.

Keywords: C−H activation; density functional calculations; homogeneous catalysis; selectivity maps; volcano plots.

Scheme 1

Cp^XRh^III‐catalyzed, solvent‐induced modulation of selectivity in the reaction of N‐enoxyphthalimides with alkenes, where TFE results in cyclopropanation and methanol in carboamination products.

Scheme 2

Catalytic cycles leading to formation of the carboamination (red) and cyclopropanation (blue) products.

Figure 1

Overview of the catalytic cycle steps leading to the carboamination (red) and cyclopropanation (blue) products. Free energies shown here are for the Rh−L2 (Cp*Rh^III) species in methanol (carboamination, red) and TFE (cyclopropanation, blue) computed at the B3PW91‐D3(BJ)/def2‐TZVP//M06/def2‐SVP level (see Computational Details for full protocol).

Figure 2

Structures of different cyclopentadienyl ligands used in this study.

Figure 3

Volcano plots for (a) the carboamination pathway in methanol solvent, (b) the cyclopropanation pathway in methanol solvent, (c) the carboamination pathway in TFE solvent, (d) the cyclopropanation pathway in TFE solvent. Vertical lines delineate regions of the volcano where the energy span is controlled by different turnover determining intermediates/transition states (TDI/TDTS): for (a/c) I [TDI: A5, TDTS: TS(A5,A6)], II [TDI: Reactants, TDTS: RO‐TS1], III [TDI: Reactants, TDTS: TS(A3,A4)], for (b/d) I [TDI: P4, TDTS: TS(1,P2)], II [TDI: P4, TDTS: TS(P4,1)], III [TDI: Reactants, TDTS: TS(1,P2)], IV [TDI: Reactants, TDTS: TS(P2,P3)]. Enlargements of each volcano showing the location of the individual catalysts are given in the Supporting Information (Figure S1‐S3). Note the dotted lines in (c) are present to illustrate the change in volcano shape in moving from methanol to TFE solvent.

Figure 4

(a) Selectivity map of the competing carboamination and cyclopropanation pathways. Dark blue indicates strong preference for the cyclopropanation pathway and dark red strong preference for the carboamination pathway. Note the lighter blue/red as well as white areas indicate regions of energetic competition between the different pathways. (b) Activity map indicating the energy span of the two competing pathways. Warmer colors indicate more facile catalytic process. Maps are derived from the 3D volcanoes shown in Supporting Information Figure S6. Enlargements showing the location of the individual catalysts are given in Supporting Information Figure S7 and S8.

Figure 5

Experimental reaction outcome as a function of solvent for the Rh−L2 catalyst. The experimentally observed decrease in carboamination:cyclopropanation (CA : CP) ratio as the solvent is changed is predicted by the selectivity map.

Figure 6

Relative activity vs. selectivity for the 42 catalysts tested in (a) methanol and (b) TFE. Catalysts favoring carboamination are colored in red, those favoring cyclopropanation are colored in blue. Species further from the dashed vertical line, which represents lack of selectivity, are predicted to be more selective for one specific product.

Scheme 3

Formation of cyclometalated complex IrL10a. Crystal structure of IrL10a as ORTEP drawing with 50 % probability thermal ellipsoids.