Intramolecular Friedel–Crafts Acylation Reaction Promoted by 1,1,1,3,3,3-Hexafluoro-2-propanol

Abstract

Simple dissolution of an arylalkyl acid chloride in 1,1,1,3,3,3-hexafluoro-2-propanol promotes an intramolecular Friedel-Crafts acylation without additional catalysts or reagents. This reaction is operationally trivial in both execution and product isolation (only requiring concentration followed by purification) and accommodates a broad range of substrates. Preliminary studies that bear upon potential reaction mechanisms are reported.

The Wonderful Chemistry of Trifluoromethyl α‐Haloalkenyl Ketones

“…Recently, intramolecular Friedel-Crafts acylation promoted by 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as a good H-bond donor was reported. [19] To confirm the hypothesis we next examined reactions between secondary amines and bromoenones possessing metasubstituted benzene rings. A priori, in these cases the electrophilic attack can occur at both adjacent positions.…”

“…Probably, this is the first example in which electrophilic aromatic substitution occurs without the addition of any acidic catalyst. Recently, intramolecular Friedel–Crafts acylation promoted by 1,1,1,3,3,3‐hexafluoropropan‐2‐ol (HFIP) as a good H‐bond donor was reported …”

“…To answer this question and to gain better understanding of the mechanism of indene core assembly we studied the reaction carefully with the aid of 1D and 2D NMR spectroscopy. Thus, the NMR monitoring ( 1 H, 19 F, 13 C) allowed us to detect the formation of captodative aminoenones 6 as key intermediates in a cascade of transformations (Scheme 2). Evidently, their formation can be easily explained in terms of the same scheme that had previously been proposed for reactions between non-fluorinated haloenones or -enals and secondary amines.…”

Regiodivergent Aromatic Electrophilic Substitution Using Nitrosoarenes in Hexafluoroisopropanol: A Gateway for Diarylamines andp‐Iminoquinones Synthesis

“…In this regard, the Lewis acid-mediated or catalyzed Friedel-Crafts (FC) reactions constitute a conventional route to deliver industrially relevant functionalized arenes with structural diversity via CÀ C bond formation. [1] Recently, in search of a milder, efficient and benign activator, fluorinated alcohol 1,1,1,3,3, has emerged as a potential alternative to promote intra-and intermolecular FC acylation as well as FC alkylation with large set of electrophiles, such as acid chlorides, [2] allylic alcohols, [3] benzyl alcohols/halides, [4] epoxides, [5] and even cyclopropane [6] via ring-opening (Scheme 1, left side). The exotic reactivity of HFIP has been ascribed to its mild acidity, low nucleophilicity, the high dielectric constant for cation stabilization and moreover, strong hydrogen-bond donor ability.…”

“…[12,13] While diarylamines are synthesized by transition-metal catalyzed CÀ N coupling [14] or radicalbased direct CÀ H aminations including photoredox catalysis, [15] iminoquinones are usually obtained via oxidation of aniline derivatives. [16] However, this metal-free approach is portrayed by: (1) direct synthesis of diarylamines without requiring additional reagent or treatment for NÀ O bond cleavage (stepeconomic); (2) rarely explored HFIP-activated double CÀ H oxidation of arene via two consecutive [2,3] sigmatropic rearrangement in nitroso-chemistry for the direct synthesis of p-iminoquinones; (3) switching of regioselectivity by altering reactants and imperative role of HFIP in the activation of nitrosoarene (sometimes, the catalytic amount of TfOH is needed for piminoquinones); (4) easy recovery via rotary evaporator and reuse of HFIP solvent.…”