Homotropic Cooperativity in Iron-Catalyzed Alkyne Cyclotrimerizations

Abstract

Enhancing catalytic activity through synergic effects is a current challenge in homogeneous catalysis. In addition to the well-established metal-metal and metal-ligand cooperation, we showcase here an example of self-activation by the substrate in controlling the catalytic activity of the two-coordinate iron complex [Fe(2,6-Xyl₂C₆H₃)₂] (1, Xyl = 2,6-Me₂C₆H₃). This behavior was observed for aryl acetylenes in their regioselective cyclotrimerization to 1,2,4-(aryl)-benzenes. Two kinetically distinct regimes are observed dependent upon the substrate-to-catalyst ratio ([RC≡CH]₀/[1]₀), referred to as the low ([RC≡CH]₀/[1]₀ < 40) and high ([RC≡CH]₀/[1]₀ > 40) regimes. Both showed sigmoidal kinetic response, with positive Hill indices of 1.85 and 3.62, respectively, and nonlinear Lineweaver-Burk replots with an upward curvature, which supports positive substrate cooperativity. Moreover, two alkyne molecules participate in the low regime, whereas up to four are involved in the high regime. The second-order rate dependence on 1 indicates that binuclear complexes are the catalytically competent species in both regimes, with that in the high one being 6 times faster than that involved in the low one. Moreover, Eyring plot analyses revealed two different catalytic cycles, with a rate-determining step more endergonic in the low regime than in the high one, but with a more ordered transition state in the high regime than in the low one.

Figure 1

Two-coordinate iron complexes as catalysts for alkyne cyclotrimerization, R = Me₃Si, dipp; dipp = 2,6-ⁱPr₂C₆H₃.

Figure 2

Conversion (%) vs time (min) plots (entries 1–4, left) and time-adjusted profiles (entries 1–3, right) for the cyclotrimerization of PhC≡CH (S) catalyzed by 1. Experimental conditions and colors correspond to that shown in the figure. Dioxane (5 μL, 0.058 mmol) was used as internal standard. Dashed lines are for visual aid.

Scheme 1. Phenylacetylene Cyclotrimerization Catalyzed by Complex 1

Figure 3

(a) Sigmoidal shape of the plot V₀vs [PhC≡CH]₀ and the simulated best fit (black line) for all of the experimental data: V_max = 0.040 ± 0.0016 M min^–1, K_0.5 = 1.17 ± 0.031 M, h = 3.62 ± 0.20 M. (b) Linear plot of the Hill equation clearly showing two straight lines for V_max = 0.040 M min^–1. Experimental (circles) and simulated (lines) V₀vs [PhC≡CH]₀ plots for the high (c) and low (d) regimes, respectively. Parameters for the simulations of (c) and (d) are included in the green/red squares, respectively. Experimental conditions: [1]₀ = 0.0133 M, T = 60 °C.

Figure 4

Adjusted normalized time scale plots showing the overlapping of the profiles for a partial order in the catalyst of 2. The experimental conditions can be found in Table S2: green circle (run 1), red diamond (run 2), orange diamond (run 3), blue diamond (run 4), pink diamond (run 5), light blue circle (run 6), and yellow circle (run 7). [1]₀ = 0.0133 M corresponds to the reference trace (run 2).

Figure 5

Left: Plot of 1/[PhC≡CH] (M^–1) vs time (min) in the absence of additives (black diamonds) and with 0.2 mol-equiv of PMe₃ relative to 1 (blue circles). Right: Eyring plots for the high (green) and low (red) regimes over the temperature range of 40–100 °C.

Scheme 2. Proposed Preequilibria Undergone by Complex 1 and PhC≡CH; L = 2,6-Xyl₂C₆H₃

Scheme 3. Proposed Catalytically Active Binuclear Species in the Low and High Regimes; L = 2,6-Xyl₂C₆H₃

Figure 6

Left: Conversion (%) vs time (min) plot for acetylene cyclotrimerization catalyzed by 1. Experimental conditions: [1]₀ = 0.0130 M, [alkyne]₀ = 1.33 M, T = 60 °C, solvent = C₆D₆. Dashed lines are for visual aid. Right: Plot of V₀ obtained for the different alkynes vs their corresponding Hammett constants (σ_p).