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. 2012 Mar 2;77(5):2486-95.
doi: 10.1021/jo300181f. Epub 2012 Feb 8.

Mechanistic basis for high reactivity of (salen)Co-OTs in the hydrolytic kinetic resolution of terminal epoxides

Lars P C Nielsen  1 , Stephan J Zuend, David D Ford, Eric N Jacobsen
Affiliations

Mechanistic basis for high reactivity of (salen)Co-OTs in the hydrolytic kinetic resolution of terminal epoxides

Lars P C Nielsen et al. J Org Chem. .

Abstract

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co-OH catalyst and a Lewis acidic (salen)Co-X catalyst. The commonly used (salen)Co-OAc and (salen)Co-Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co-OH and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co-OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co-X precatalysts and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co-OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction.

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Figures

Figure 1
Figure 1
Rate dependence of epoxide hydrolysis on [cat]tot 2 and %-conversion. Plots of the rate of hydrolysis of (R)-1,2-epoxyhexane ([epoxide]i = 5.63 M) versus [(S,S)-(salen)Co–OH]2 in 1,2-hexanediol ([diol]i = 2.18 M) at different %-conversion of water ([H2O]i = 2.82 M). The catalyst was generated by aging (S,S)-(salen)Co–Cl in epoxide for 1 h prior to addition of water. The black curves represent least-squares fits to f(x) = a x, 20 % conversion, a = 1.92 ± 0.01 M−1 s−1; 50 % conversion, a = 1.314 ± 0.009 M−1 s−1; 80 % conversion, a = 0.597 ± 0.006 M−1 s−1.
Figure 2
Figure 2
Rates of epoxide hydrolysis with different (salen)Co(III) precatalysts. Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 6.0 M) in 1,2-hexanediol versus time in 1,2-hexanediol ([H2O]i = 3.4 M). In each experiment, (R,R)-(salen)Co–X (0.15 mol %) was added to a reaction mixture containing epoxide, diol, and water as an 83.0 mM CH2Cl2 solution. The indicated times represent the length of time required to achieve 95% conversion of water with each precatalyst.
Figure 3
Figure 3
Plot of the maximum rate hydrolysis of (S)-1,2-epoxyhexane as a function of different ratios of (salen)Co–OH and (salen)Co–SbF6, at a constant total [(salen)Co(III)]. The (salen)Co–OH is generated by premixing (salen)Co–Cl and epoxide followed by addition of water. The curve represents a least-squares fit to f(x) = a x2 + b x + c, a = −1620 ± 60, b = 1540 ± 60, c = 30 ± 10 mJ s−1.
Figure 4
Figure 4
Heat of mixing experiments showing the heat flow spikes due to addition of H2O (85 μL) and CH2Cl2 (150 μL) to a solution of 1,2-epoxyhexane (1.00 mL) and 1,2-hexanediol (300 μL). Nearly identical effects are observed when the order of addition is reversed.
Figure 5
Figure 5
Rate dependence on the time between addition of (salen)Co–Cl precatalyst and water to a solution of epoxide. Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (R,R)-(salen)Co–Cl (0.15 mol %) was added to the reaction mixture as an 83 mM CH2Cl2 solution; water was added subsequently after the indicated delay time.
Figure 6
Figure 6
Rate dependence on the time between addition of (salen)Co–OAc and water to a solution of epoxide. Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (R,R)-(salen)Co–OAc (0.15 mol %) was added to the reaction mixture as an 83 mM CH2Cl2 solution; water was added subsequently after the indicated delay time.
Figure 7
Figure 7
Rate dependence on the time between addition of (salen)Co–OTs and water to a solution of epoxide. Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (R,R)-(salen)Co–OTs (0.15 mol %) was added to the reaction mixture as an 83 mM CH2Cl2 solution; water was added subsequently after the indicated delay time.
Figure 8
Figure 8
Rate dependence on the nature of the counterion, X, in HKR experiments in which catalyst was added as the last reagent (i.e., 0 min delay time). Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus time in 1,2-hexanediol ([H2O]i = 3.1 M). In each experiment, (R,R)-(salen)Co–X (0.15 mol %) was added to a reaction mixture containing epoxide, diol, and water as an 83 mM CH2Cl2 solution.
Figure 9
Figure 9
Rate dependence on the nature of the counterion, X, with a 180 min delay time between catalyst and water addition. Plot of the rates of hydrolysis of (S)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (R,R)-(salen)Co–OTs (0.15 mol %) was added to the reaction mixture as an 83 mM CH2Cl2 solution; water was added subsequently after the indicated delay time.
Figure 10
Figure 10
Rate dependence on delay time between addition of water and 3d. Plot of the rates of hydrolysis of (R)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (S,S)-(salen)Co–Cl (0.15 mol %) was added to the reaction mixture and aged for 45 min, followed by water; 3d (0.15 mol %) was added as a solution in CH2Cl2 subsequently after the indicated delay time. The black curve is derived from an experiment in which neither 3d nor CH2Cl2 was added.
Figure 11
Figure 11
Rate dependence on delay time between addition of 3d and water. Plot of the rates of hydrolysis of (R)-1,2-epoxyhexane ([epoxide]i = 5.4 M) in 1,2-hexanediol versus conversion of water ([H2O]i = 3.1 M) in 1,2-hexanediol. In each experiment, (S,S)-(salen)Co–Cl (0.15 mol %) was added to the reaction mixture and aged for 45 min, followed by 3d (0.15 mol %) as a solution in CH2Cl2; water was added subsequently after the indicated delay time. The black curve is derived from an experiment in which CH2Cl2 is added, but not 3d.
Figure 12
Figure 12
Catalyst partitioning in the (salen)Co–OTs-catalyzed HKR. The green and blue arrows represent two different methods of generating a highly active catalyst mixture.
Scheme 1
Scheme 1
Hydrolytic kinetic resolution of terminal epoxides catalyzed by (salen)Co(III) complexes
Scheme 2
Scheme 2
Proposed mechanism of catalysis for HKR reactions catalyzed by mixtures of (salen)Co–X and (salen)Co–OH
Scheme 3
Scheme 3
Delayed-addition of water to probe catalyst partitioning.
Scheme 4
Scheme 4
Experiment to probe the viability of the equilibrium in eq 2.
Scheme 5
Scheme 5
Accessing the (salen)Co–OTs/(salen)Co–OH equibrium from tosylate addition complex 1h.
See this image and copyright information in PMC

References

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    1. For recent reviews of applications of the HKR reaction in industrial and natural products synthesis, see: Kumar P, Naidu V, Gupta P. Tetrahedron. 2007;63:2745–2785.Furukawa Y, Suzuki T, Mikami M, Kitaori K, Yoshimoto H. J Synth Org Chem Japan. 2007;65:308–319.Kumar P, Gupta P. Synlett. 2009:1367–1382.

    1. Phenols: Ready JM, Jacobsen EN. J Am Chem Soc. 1999;121:6086–6087.Carbamates: Bartoli G, Bosco M, Carlone A, Locatelli M, Melchiorre P, Sambri L. Org Lett. 2004;22:3973–3975.Azides: Martínez LE, Leighton JL, Carsten DH, Jacobsen EN. J Am Chem Soc. 1995;117:5897–5898.Anilines: Bartoli G, Bosco M, Carlone A, Locatelli M, Massaccesi M, Melchiorre P, Sambri L. Org Lett. 2004;6:2173–2176.Indoles: Bandini M, Cozzi PG, Melchiorre P, Umani-Ronchi A. Angew Chem Int Ed. 2004;43:84–87.

    1. For reviews see: Jacobsen EN. Acc Chem Res. 2000;33:421–431.Nielsen LPC, Jacobsen EN. In: In Aziridines and Epoxides in Organic Synthesis. Yudin AK, editor. Chapter 7 Wiley-VCH; Weinheim: 2006.

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