Enantioselective Friedel–Crafts Reactions in Water Using a DNA‐Based Catalyst

Taking the plunge : The first example of a Lewis acid catalyzed asymmetric Friedel–Crafts alkylation with olefins in water is described. By using loadings of a DNA‐based copper catalyst as low as 0.15 mol %, good yields and excellent enantioselectivities were obtained in the reaction of α,β‐unsaturated 2‐acyl imidazoles with heteroaromatic π nucleophiles. dmbpy=4,4′‐dimethyl‐2,2′‐bipyridine.

     

Catalytic Friedel–Crafts Reactions of Highly Electronically Deactivated Benzylic Alcohols

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 Brønsted 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.     

Structurally Divergent Lithium Catalyzed Friedel–Crafts Reactions on Oxetan‐3‐ols: Synthesis of 3,3‐Diaryloxetanes and 2,3‐Dihydrobenzofurans

The first examples of 3,3‐diaryloxetanes are prepared in a lithium‐catalyzed and substrate dependent divergent Friedel–Crafts reaction. para‐Selective Friedel–Crafts reactions of phenols using oxetan‐3‐ols afford 3,3‐diaryloxetanes by displacement of the hydroxy group. These constitute new isosteres for benzophenones and diarylmethanes. Conversely, ortho‐selective Friedel–Crafts reactions of phenols afford 3‐aryl‐3‐hydroxymethyl‐dihydrobenzofurans by tandem alkylation–ring‐opening reactions; the outcome of the reaction diverging to structurally distinct products dependent on the substrate regioselectivity. Further reactivity of the oxetane products is demonstrated, suitable for incorporation into drug discovery efforts.     

Highly Enantioselective Synthesis of β‐Heteroaryl‐Substituted Dihydrochalcones Through Friedel–Crafts Alkylation of Indoles and Pyrrole

A highly enantioselective Friedel–Crafts (F–C) alkylation of indoles and pyrrole with chalcone derivatives catalyzed by a chiral N,N′‐dioxide–Sc(OTf)₃ complex has been developed that tolerates a wide range of substrates. The reaction proceeds in moderate to excellent yields and high enantioselectivities (85–92 % enantiomeric excess) using 2 mol % (for indole) or 0.5 mol % (for pyrrole) catalyst loading, which showed the potential value of the catalyst system. Meanwhile, a strong positive nonlinear effect was observed. On the basis of the experimental results and previous reports, a possible working model is proposed to explain the origin of the activation and asymmetric induction.     

Highly efficient bimetallic iron‐palladium catalyzed Michael‐type Friedel–Crafts reactions of indoles with chalcones

Iron–palladium is a superior bimetallic catalyst in the presence of acetylacetone (Acac) with remarkable synergistic effect for the Michael‐type Friedel–Crafts reactions of indoles with chalcones. This catalytic system has the advantages of mild reaction conditions, smaller amount of metal salts, high yields of the desired products and operational simplicity, which make it a useful and promising process for the synthesis of indole derivatives. Copyright © 2009 John Wiley & Sons, Ltd.     

Organocatalytic Enantioselective Aza‐Friedel–Crafts Reaction of Cyclic Ketimines with Pyrroles using Imidazolinephosphoric Acid Catalysts

Organocatalytic enantioselective aza‐Friedel–Crafts reactions of cyclic ketimines with pyrroles or indoles were catalyzed by imidazoline/phosphoric acid catalysts. The reaction was applied to various 3H‐indol‐3‐ones to afford products in excellent yields and enantioselectivities. The chiral catalysts can be recovered by a single separation step using column chromatography and are reusable without further purification. Based on the experimental investigations, a possible transition state has been proposed to explain the origin of the asymmetric induction.     

Surfactant‐Encapsulated Polyoxometalates as Immobilized Supramolecular Catalysts for Highly Efficient and Selective Oxidation Reactions

A type of interesting immobilized supramolecular catalysts based on surfactant‐encapsulated polyoxometalates has been developed for oxidation reactions. Through a sol‐gel process with tetraethyl orthosilicate, hydroxyl‐terminated surfactant‐encapsulated polyoxometalate complexes have been covalently and uniformly bound to a silica matrix with unchanged complex structure. The formed hybrid catalysts possess a defined hydrophobic nano‐environment surrounding the inorganic clusters, which is conducive to compatibility between the polyoxometalate catalytic centres and organic substrates. The supramolecular synergy between substrate adsorption, reaction, and product desorption during the oxidation process has been found to have an obvious influence on the reaction kinetics, with the activity of the catalyst being greatly improved. The supramolecular catalysts performed effectively in the selective oxidation of several different kinds of organic compounds, such as alkenes, alcohols, and sulfides, and the main products were the corresponding epoxides, ketones, sulfoxides, and sulfones. More significantly, the catalyst could be easily recovered by simple filtration, and the catalytic activity was well retained for at least five cycles. Finally, the present strategy has proved to be a general route for the fabrication of supramolecular hybrid catalysts containing common polyoxometalates suitable for various purposes.     

Electrophilic Aromatic Substitution with Silicon Electrophiles: Catalytic Friedel–Crafts C−H Silylation

Electrophilic aromatic substitution is a fundamental reaction in synthetic chemistry. It converts C−H bonds of sufficiently nucleophilic arenes into C−X and C−C bonds using either stoichiometrically added or catalytically generated electrophiles. These reactions proceed through Wheland complexes, cationic intermediates that rearomatize by proton release. Hence, these high‐energy intermediates are nothing but protonated arenes and as such strong Brønsted acids. The formation of protons is an issue in those rare cases where the electrophilic aromatic substitution is reversible. This situation arises in the electrophilic silylation of C−H bonds as the energy of the intermediate Wheland complex is lowered by the β‐silicon effect. As a consequence, protonation of the silylated arene is facile, and the reverse reaction usually occurs to afford the desilylated arene. Several new approaches to overcome this inherent challenge of C−H silylation by S_EAr were recently disclosed, and this Minireview summarizes this progress.     

Temperature Dual Enantioselective Control in a Rhodium‐Catalyzed Michael‐Type Friedel–Crafts Reaction: A Mechanistic Explanation

By changing the temperature from 283 to 233 K, the S (99 % ee) or R (96 % ee) enantiomer of the Friedel–Crafts (FC) adduct of the reaction between N‐methyl‐2‐methylindole and trans‐β‐nitrostyrene can be obtained by using (S_Rh,R_C)‐[(η⁵‐C₅Me₅)Rh{(R)‐Prophos}(H₂O)][SbF₆]₂ as the catalyst precursor. This catalytic system presents two other uncommon features: 1) The ee changes with reaction time showing trends that depend on the reaction temperature and 2) an increase in the catalyst loading results in a decrease in the ee of the S enantiomer. Detection and characterization of the intermediate metal–nitroalkene and metal–aci‐nitro complexes, the free aci‐nitro compound, and the FC adduct‐complex, together with solution NMR measurements, theoretical calculations, and kinetic studies have allowed us to propose two plausible alternative catalytic cycles. On the basis of these cycles, all the above‐mentioned observations can be rationalized. In particular, the reversibility of one of the cycles together with the kinetic resolution of the intermediate aci‐nitro complexes account for the high ee values achieved in both antipodes. On the other hand, the results of kinetic measurements explain the unusual effect of the increment in catalyst loading.     

Mild Friedel–Crafts Reactions inside a Hexameric Resorcinarene Capsule: C−Cl Bond Activation through Hydrogen Bonding to Bridging Water Molecules

A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self‐assembled cage was exploited to promote the Friedel–Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen‐bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C?Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N‐methylpyrrole is preferentially benzylated in the unusual β‐position while mesitylene reacts faster than 1,3‐dimethoxybenzene despite the greater π‐nucleophilicity of the latter compound.