1. Introduction
Controlling reaction rate and selectivity is a long-standing goal and challenge in chemistry.1-3 Conventional ways to control chemical reactions include heating,4 stirring, using solvents5 or catalysts.6Recently, inspired by the pioneering work of Shaik and co-workers,7-9 attention has turned to the manipulation of activation energy barriers and the stabilization of reactive species in chemical reactions by oriented external electric fields (OEEFs).10,11 The influence of OEEFs upon chemical reaction performance has raised a number of scientifically interesting questions, and increasing evidence has shown that OEEFs could be employed as smart reagents and catalysts in chemistry.10,12-15 It was proposed by Meir et al.8 that organic reactions can be theoretically accelerated when an external electric field is oriented along the “reaction axis” which enhances the electron flow, leading to a lower reaction barrier and the stabilization of transition states. This simulated prediction was experimentally demonstrated by Aragones et al. in an OEEF promoted Diels-Alder reaction at the single molecule scale.16 Huang et al. also proved this idea by selective catalysis of a Diel-Alder addition reaction with an external electric field oriented along the reaction coordinate.17 More importantly, Wang et al. predicted that the reaction enantioselectivity may be controlled by aligning the electric field along the dipole moment of the reactants.2 While it is potentially significant for asymmetric synthesis, there is no direct experimental evidence so far to support it.
Despite the promising prospects, there are two major challenges to be met in order to utilize OEEFs for controlling reaction rates and selectivity. One requirement is to orient the electric field along the reaction axis,10 the other is the high electric field strength (107 to 109V/m).17,18 At molecular level, these challenges can be addressed by using scanning tunneling microscope break junction (STMBJ) techniques16,19,20 or mechanically controllable break junction (MCBJ) techniques.17,21,22 Nevertheless, when conducting experiments on a bulk scale, the question of how to align the electric field along the reaction axis arises when thousands of reactant molecules are randomly oriented in the reaction system. Furthermore, applying thousands of volts to a lab-scale (or even larger scales) reactor could pose safety issues. Therefore, the significance of OEEFs on controlling reaction rates and selectivity experimentally in bulk quantity reactions for organic synthesis remains understudied. However, apart from lowering the reaction barrier with huge energy input, a simple way to manipulate the reaction rates by external electric fields is to control the diffusion of reactive species in the reaction system,23 and alter the local concentration of reactants.24 This has been validated in our previous study that the reaction rate can be either promoted or inhibited by simply flipping the orientation of the external electric field.25
To further explore the possibilities of controlling reaction rate and even selectivity with external electric field on bulk scales, catalytic transfer hydrogenation of acetophenone was studied in a biphasic liquid system. Previous studies showed that the phase transfer hydrogenation of acetophenone with sodium formate as hydrogen source is a mass transfer limited reaction happening at the organic-aqueous interface.25,26 When an external electric field was applied, the charged reactive species could be either transferred to the interface to promote the reaction or constrained in the corresponding liquid phases decelerating the reaction by the electrostatic forces.25 This raises the possibility of manipulating the reaction rates by controlling the diffusion of reactive species in the presence of varying electric field potential for interfacial reaction/catalysis in a biphasic liquid system.
In this contribution, we have demonstrated the ability of external electric fields to control reaction rates in the catalytic phase transfer hydrogenation of acetophenone and its influence on reaction enantioselectivity. Mathematical modeling and simulation results further support the controllable migration of reactive species under external electric fields. While evincing fundamental principles, the results also show the possible decomposition effects of the external electric field on the catalyst when applied in the negative orientation, resulting in lower reaction conversion and enantioselectivity. In general, this work shows the importance of comprehensively understanding the role of external electric field in organic synthesis and catalysis on bulk scale.