Studies on the Origin of the Stabilizing Effects of Fluorinated Alcohols and Weakly Coordinated Fluorine-Containing Anions on Cationic Reaction Intermediates

Abstract

Many synthetic methods that use fluorinated alcohols as solvents have been reported, and the fluorinated alcohols have been found to be crucial to the success of these methods. In addition, there have been reports indicating that adding a weakly coordinated fluorine-containing anion, such as BF 4− , PF 6 − , or SbF 6 − , to fluorinated alcohols can improve yields. The boosting effect of fluorinated alcohols is attributed mainly to hydrogen bond activation. A few studies have suggested that the very polar fluorinated alcohols can stabilize cationic reaction intermediates. However, how they do so and why weakly coordinated fluorine-containing anions improve yields have not been studied in depth. Here, we used quaternary ammonium cations, a quaternary phosphonium cation, and a triaryl-substituted carbocation as models for short-lived cationic intermediates and studied the possible interactions of these cations with fluorinated alcohols and BF 4 − , PF 6 − , or SbF 6 − . On the basis of the results, we propose that the C−F dipoles of fluorinated alcohols and the E−F dipoles (where E is B, P, or Sb) of weakly coordinated fluorinecontaining anions stabilized these cations by intermolecular charge−dipole interactions. We deduced that in the same fashion the C−F and E−F dipoles can thermodynamically stabilize cationic reaction intermediates.

Tandem Cooperative Friedel-Crafts Reaction of Aldehydes with Electron Deficient Arenes Through Catalyst-Activation via Hydrogen Bonding Network

“…Thus, at room temperature, using 10.0 mol% pTSA, the diarylmethane ( 6) could be synthesized in excellent yield (87%) within 10 h. However, interestingly, when the reaction was performed in fluorinated alcohols like HFIP, the reaction was very clean and essentially gave the quantitative yield of the product analyzed by NMR studies. This could either be due to the enhanced hydrogen bond donor ability of the fluoroalcohols compared to common alcohol solvents like methanol (MeOH) or ethanol (EtOH) or maybe due to the strong ionizing power of the fluoroalcohol and hence stabilizing the polar intermediates (thus enhancing the reaction rate) formed during the course of the reaction [24][25][26][27] . The polarity effect might not be important in this case since no significant improvement in the reaction rate as well as the yield was observed when HFIP was replaced by EtOH or 2,2,2-trifluroethanol (TFE), although the dielectric constant of these two polar protic solvents [ε(EtOH) = 24.3; ε(TFE) = 26.7] is higher than HFIP (ε = 16.7) (SI).…”

“…Towards such pursuits, here in this work, we have developed a new strategy where the reaction proceeds via "catalyst-activation" 23 followed by "substrate-activation". Here the catalyst was activated by the solvent, HFIP, through hydrogen bonding network [23][24][25][26][27] . Further, recent literature reports also suggests that HFIP interacts with the arene molecules through OH-π and CH-π interactions 24 .…”

“…Here the catalyst was activated by the solvent, HFIP, through hydrogen bonding network [23][24][25][26][27] . Further, recent literature reports also suggests that HFIP interacts with the arene molecules through OH-π and CH-π interactions 24 . The combined effect of catalyst activation by HFIP followed by substrate activation resulted in achieving our goal as discussed in this paper.…”

Bioinspired Synthesis of Spirochensilide A from Lanosterol

“…For example, when Zn­(OTf) 2 was used as a promoter, 16 was obtained as the sole product in 78% yield (entry 1). Fluorinated alcohols, such as 2,2,2-trifluoroethanol (TFE), 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and perfluoro- tert -butanol (PFTB), also failed to afford the desired product 17 (entry 2). Interestingly, when 1-ethyl-3-methylimidazolium tetrafluoroborate ([EMIM]­BF 4 ) was used, we obtained ketone 22 , the product of C16 hydride migration (entry 3).…”

“…OH with TMSOTf and subsequent DIBAL-H reduction of the methyl ester afforded the desired aldehyde. Treatment of the aldehyde with ethyl 2-(diethoxyphosphoryl)propanoate(19) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) resulted in a Horner−Wadsworth−Emmons reaction that produced ester 20 in 72% yield over three steps.…”