Transition-State Expansion: A Quantitative Model for Counterion Effects in Ionic Reactions

Abstract

Summary Ionic reactions are the most common reactions used in chemical synthesis. In relatively low dielectric constant solvents (e.g., dichloromethane, toluene), ions usually exist as ion pairs. Despite the importance of counterions, a quantitative description of how the paired 'counterion' affects the reaction kinetic is still elusive. We introduce a general and quantitative model, namely transition-state expansion (TSE), that describes how the size of a counterion affects the transition-state structure and the kinetics of an ionic reaction. This model could rationalize the counterion effects in nucleophilic substitutions and gold-catalyzed enyne cycloisomerizations.

Unbalanced-Ion-Pair-Catalyzed Nucleophilic Fluorination Using Potassium Fluoride

“…11,12 Even in highly polar aprotic solvents such as DMF, the solubility and degree of dissociation are small. 13 To increase the reactivity of K + F − and to lessen the twisted transition state (TS-2 in Figure 1a), the counterion K + was replaced with a highly bulky cation (e.g., Bu 4 N + ), 14 but this substitution increased the cost and led to side reactions, such as eliminations, because of the higher basicity. 15 Chelators with a high affinity to K + such as cryptands (e.g., K 222 ), crown ethers (e.g., 18-crown-6, BTC5A 16 ), and bis-terminal hydroxy polyethers 17 have been utilized (Figure 1a).…”

“…23,24 As a result, the reactivity of the paired K + F − in an S N 2 reaction will be very low because of the small size of K + . 14 Based on our model, we are now proposing a new concept for nucleophilic fluorination: an unbalanced ion-pairpromoter-assisted nucleophilic substitution pathway (Figure 1b). In our definition of an "unbalanced" ion pair, the cation part is highly bulky, and the positive charge is delocalized or embedded; the anion counterpart, though, is relatively small, and the negative charge is localized and can be accessed easily.…”

“…Recently, we introduced a general and quantitative model, namely, transition state expansion (TSE), that describes how the size of a counterion affects the transition state structure and the kinetics of an ionic reaction . According to our model, in an S N 2 reaction, in the presence of a paired counterion, the K + F – ion pair has to adopt a highly twisted transition state (Figure , TS-1). , As a result, the reactivity of the paired K + F – in an S N 2 reaction will be very low because of the small size of K + . Based on our model, we are now proposing a new concept for nucleophilic fluorination: an unbalanced ion-pair-promoter-assisted nucleophilic substitution pathway (Figure b).…”

Gold(I)-Catalyzed Benzylic C(sp3)-H Functionalizations: Product Bifurcation towards Indole[a]- and [b]-Fused Polycycles

“…67 The decomposition of tetraphenylborate could play an important role in this process, 70 but also a counter-cation effect is conceivable that would influence the ionic character of the indole scaffold. 75 The spiro-fused pentacycle 8c was obtained exclusively, in 62% yield, by employing NaBARF. Finally, we employed a distal benzylic functionalization to generate an indole-fused seven-membered ring.…”

Gold(I)-Catalyzed Benzylic C(sp3)-H Functionalizations: Product Bifurcation towards Indole[a]- and [b]-Fused Polycycles

“…[71] The decomposition of tetraphenylborate could play an important role in this process, [72] but also a counter-cation effect is conceivable that would influence the ionic character of the indole scaffold. [73] The spiro-fused pentacycle 8c was obtained exclusively, in 62% yield, by employing NaBARF.…”