Activation of Electron-Deficient Quinones Through Hydrogen-Bond-Donor-Coupled Electron Transfer
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CitationTurek, Amanda Katherine. 2015. Activation of Electron-Deficient Quinones Through Hydrogen-Bond-Donor-Coupled Electron Transfer. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.
AbstractQuinones are organic oxidants that play important roles in biological contexts and find wide application in organic synthesis. They are known to be activated toward electron transfer through hydrogen bonding, which has largely been observed for Lewis basic, weakly oxidizing quinones. Comparable activation through H-bonding is more difficult to achieve when more reactive, electron-deficient quinones are used, as these intrinsically weaker Lewis bases are less prone to engage in H-bonding interactions.
Herein, we describe the successful application of HBD-coupled electron transfer as a strategy to activate electron-deficient quinones. A systematic investigation of several small-molecule HBDs allowed examination of the effects of H-bonding on electron transfer to o-chloranil, an electron-deficient quinone that lacks the intrinsic reactivity necessary to oxidize many organic substrates of synthetic interest. This study has led to the discovery that dicationic HBDs have an exceptionally large effect on the rate and thermodynamics of these electron transfer reactions.
Favorable modulation of the thermodynamics occurs as a result of the stabilization provided to the reduced quinone (Q•–) by the HBD. Electrochemical experiments have allowed quantification of the binding affinity for Q•– to each of the HBDs, as well as elucidation of the binding stoichiometry of the resulting ground-state complex. Monocationic HBDs bind to Q•– with 2:1 stoichiometry, whereas dicationic HBDs bind in a 1:1 complex. Dicationic bis-amidinium salts exhibit significantly improved binding to Q•–, offering more thermodynamic stabilization to this reduced state.
The effects of HBDs on the kinetics of electron transfer have also been evaluated under homogenous conditions. Reactions between o-chloranil and ferrocene derivatives exhibit pronounced HBD-dependent rate enhancements, with dicationic HBDs displaying the greatest effect. Relative to neutral dual HBDs, the bis-amidinium salts accelerate the rate of electron transfer by > 1012. Binding stoichiometries within the rate-limiting transition states corroborate the results determined electrochemically, and binding affinity correlates with rate enhancement was observed across the series of HBDs evaluated.
Application of HBD-coupled electron transfer in an oxidative lactonization illustrates that this strategy is applicable to catalysis of organic reactions. A dicationic HBD catalyst affords the lactone product in nearly quantitative yield within 24 h, whereas o-chloranil alone was ineffective (< 5% yield). The rates of lactonization with several HBD catalysts correlate well with the thermodynamic and kinetic trends described above. This trend indicates that the rate of the oxidative lactonization is related to the ability of the HBD to promote an electron transfer step. Potential strategies for application in enantioselective transformations and possibilities for future mechanistic investigation are presented.
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