The Nucleophilicity of Persistent α‐Monofluoromethide Anions

Abstract

α-Fluorocarbanions are key intermediates in nucleophilic fluoroalkylation reactions. Although frequently discussed, the origin of the fluorine effect on the reactivity of α-fluorinated CH acids has remained largely unexplored. We have now investigated the kinetics of a series of reactions of α-substituted carbanions with reference electrophiles to elucidate the effects of α-F, α-Cl, and α-OMe substituents on the nucleophilic reactivities of carbanions.

Enolization rates control mono- versus di-fluorination of 1,3-dicarbonyl derivatives

“…Furthermore, in related carbanion systems, the reactivity was found to be enhanced by the presence of an a-uorine atom compared to the non-uorinated carbanion. 61,62 Indeed, the effect of the a-uorine was even greater in these studies, probably because of the increased repulsion between the oxyanionic charge and uorine lone pairs in comparison to our systems.…”

The Acidities of Nucleophilic Monofluoromethylation Reagents: An Anomalous α‐Fluorine Effect

“…Finally, we correlated the p K a for FSMs and PSMs with Mayr's nucleophilicity parameters ( N ) [8] . As shown in Figure 6, a good positive correlation was identified between nucleophilicity parameter N and p K a .…”

“…Therefore, the p K a values of these reagents are crucial to understanding the corresponding carbanion formation as well as their nucleophilicities and stabilities [7] . Much to our surprise, many of the p K a values of common monofluoromethylating reagents are unknown, although the nucleophilicity parameter ( N ) for a few of them has been determined recently [8] . Herein, as part of our ongoing effort to understand the structure–reactivity relationship of fluoroalkylation reagents, [9] we report the determination of the equilibrium acidities of popularly used nucleophilic monofluoromethylating reagents and their non‐fluorinated counterparts (phenylsulfonylmethane derivatives, PSMs) by using Bordwell's classical overlapping indicator method in dimethyl sulfoxide (DMSO) solution [10] .…”

“…[7] Much to our surprise, many of the pK a values of common monofluoromethylating reagents are unknown, although the nucleophilicity parameter (N) for a few of them has been determined recently. [8] Herein, as part of our ongoing effort to understand the structure-reactivity relationship of fluoroalkylation reagents, [9] we report the determination of the equilibrium acidities of popularly used nucle-Scheme 1. Selected fluoro(phenylsulfonyl)methane-type of nucleophilic monofluoromethylation reagents.…”

Phosphine‐Catalyzed β‐Selective Conjugate Addition of α‐Fluoro‐β‐ketoamides to Allenic Esters

“…Subsequent to the first report on trifluoromethylation by Prakash and co‐workers, considerable efforts have been made for the development of this type of reaction . However, when compared to the extensively studied trifluoromethylation reactions, monofluoroalkylation reactions have largely remained unexplored . Later, the same group and others discovered that fluorinated sulfones, malonates, and α‐fluoro‐β‐keto ester derivatives could serve as attractive synthons of fluoro enolates in many organic transformations , .…”