Highly electronically deactivated benzylic alcohols, including those with a CF3 group adjacent to the OH-bearing carbon, undergo dehydrative Friedel-Crafts reactions upon exposure to catalytic Bronsted acid in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solvent. Titration and kinetic experiments support the involvement of higher order solvent/acid clusters in catalysis.

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Catalytic Friedel–Crafts Reactions of Highly Electronically Deactivated Benzylic Alcohols

https://hal.archives-ouvertes.fr/hal-02990301/document

Exploiting hexafluoroisopropanol (HFIP) in Lewis and Brønsted acid-catalyzed reactions

Fluorinated alcohols have been widely used in the synthetic organic chemistry over the past decades. The unique properties such as the strong hydrogen-bonding donor ability and low nucleophilicity allow them to promote organic reactions in the absence of any catalyst. These approaches have distinct advantages in terms of operational simplicity, practicability and environmental friendliness. Reactions promoted by fluorinated alcohols, including nucleophilic substitution reactions, annulation reactions, electrophilic reactions, dearomatization reactions, functionalization of multiple bond, epoxidation reactions and miscellaneous reactions have been summarized in this account.

Fluorinated Alcohols: Magic Reaction Medium and Promoters for Organic Synthesis.

The influence of substituents on the properties of tri- and hexafluorinated alcohols derived from 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was examined. Measurements of specific solvent−solute interactions revealed that H-bond donation (HBD) of fluorinated alcohols is sensitive to the steric hindrance of the OH group, whereas their Bronsted acidity is dependent only on the number of fluorine atoms. For hexafluorinated alcohols (HFAs), their association with amines characterized by X-ray diffraction showed that the balance between HBD and acidity is influenced by their structure. Moreover, the ability of HFAs to donate H-bonds is exerted in synclinal (sc), synperiplanar (sp), and also antiperiplanar (ap) conformations along the C−O bond. Comparison of the effects of fluorinated alcohols as promoting solvents in three reactions is reported. The positive correlation between rate constants and H-bonding donation ability for sulfide oxidation and imino Diels−Alder reaction brin...

Influence of the structure of polyfluorinated alcohols on Brønsted acidity/hydrogen-bond donor ability and consequences on the promoter effect.

In contrast to Nature that accomplishes polyene cyclizations seemingly with ease, such transformations are difficult to conduct in the lab. In our program dealing with the development of selective halogenations of alkenes, we now asserted that standard X+ reagents are perfectly suited for the biomimetic cation-π cyclization of both electron rich and poor linear polyenes in the presence of the Lewis base morpholine and the Lewis acid HFIP. The method stands out due to its broad substrate scope and practicability together with high chemical yields and excellent selectivities, even for highly challenging chloriranium-induced polyene cyclizations.

J.-F. Berrien

Papers

A crystalline H-bond cluster of hexafluoroisopropanol (HFIP) and piperidine: Structure determination by X ray diffraction