Oriented External Electric Fields and Ionic Additives Elicit Catalysis and Mechanistic Crossover in Oxidative Addition Reactions

Abstract

Judiciously applied oriented external electric fields (OEEFs) exert catalytic effects on the kinetics and improve the thermodynamics of chemical reactions. Herein, we examine the ability of OEEFs to assist catalysts and show that the rate of oxidative addition between palladium catalysts and alkyl/aryl electrophiles can be controlled by an OEEF applied along the direction of electron reorganization (the "reaction axis"). The concerted mechanism of oxidative addition proceeds through a transition state with moderate charge transfer character. We demonstrate that OEEFs along the reaction axis can control this charge transfer and impart electrostatic catalysis. When the applied field exceeds a certain critical value (∼0.15 V/Å), we observed a mechanistic crossover from the concerted to a dissociative CS N Ar type of reactivity for aryl electrophiles. To our surprise, alkyl electrophiles follow a hitherto unexplored S N 2 pathway for the reaction with large transition state stabilization at relatively low OEEFs. A valencebond state correlation diagram (VBSCD) is employed to comprehend the results. Finally, although the catalytic effect of salt additives in oxidative addition is known, its mechanism is still under debate. Our findings further show evidence that salt additives exert electric-field effects on the rate of cross-coupling reactions, and their cocatalytic effects can be judiciously reproduced by applied external electric fields. As such, we propose that the use of additives (anionic or cationic) is an experimentally viable strategy to implement external electric-field effects in routinely used oxidative addition catalysis.

How Do Metal Ions Modulate the Rate‐Determining Electron‐Transfer Step in Cytochrome P450 Reactions?

“…(equivalent to 1.0 to −1.0 V Å −1 ) and the results are shown in Figure 5. These field values are typically used in theoretical mechanistic crossover studies [61] and experimentally observed in vibrational Stark effect studies [62] …”

“…(equivalent to 1.0 to À1.0 V À1 )and the results are showni nF igure 5. These field values are typically used in theoretical mechanistic crossover studies [61] and experimentally observed in vibrational Stark effect studies. [62] The redox potential (E8), electron-transfer rate constants (log k e ), and barrier (E act )a re fairly constant at moderate field strengthsa long the y axis and change only at relatively high field values (> 0.5 V À1 ,F igure 5a nd Figure S6 in the Supporting Information).…”

Cisplatin under oriented external electric fields: A deeper insight into electrochemotherapy at the molecular level

“…Consequently, the geometric and electronic modification of cisplatin under different oriented external electric fields (OEEFs) has been detailedly studied in this work. It is recently reported that OEEFs can cause structural distortions, 18,19 induce proton transfer, 20,21 modulate NLO responses of materials, 22,23 and catalyze various reactions as smart catalysts and controllers of reaction mechanisms 24–33 . Herein, we will mainly focus on the following two questions: (a) What is the influence of OEEFs on the geometric and electronic structure of cisplatin?…”

“…It is recently reported that OEEFs can cause structural distortions, 18,19 induce proton transfer, 20,21 modulate NLO responses of materials, 22,23 and catalyze various reactions as smart catalysts and controllers of reaction mechanisms. [24][25][26][27][28][29][30][31][32][33] Herein, we will mainly focus on the following two questions: (a) What is the influence of OEEFs on the geometric and electronic structure of cisplatin? (b) How does the OEEF-induced geometric and electronic modification improve the antitumor activity of cisplatin in electrochemotherapy?…”

Quantifying Through‐Space Substituent Effects

“…[6a, 14] Such throughspace models are beginning to supersede earlier empirically derived models of aromatic interactions, [15] and numerous investigations have highlighted the importance of field effects in enzyme-catalyzed reactions [16] and synthetic organic chemistry. [17] However,c ontrasting with the success of empirically derived Hammett substituent constants in accounting for reactivity in aw ide range of contexts,h igh-quality experimental data quantifying through-space substituent effects are surprisingly limited.…”