Enantioselective Friedel–Crafts Alkylation of Indoles with Alkylidene Malonates Catalyzed by N,N′‐Dioxide–Scandium(III) Complexes: Asymmetric Synthesis of β‐Carbolines

An efficient catalytic asymmetric Friedel–Crafts alkylation of indoles with alkylidene malonates has been developed by using a chiral N,N′‐dioxide–Sc(OTf)₃ complex as the catalyst (see scheme). Some optically active intermediates containing the indole skeleton have been synthesized, such as indolepropionic acid, tryptamines, and β‐carbolines. The coordination between the scandium atom and the chiral N,N′‐dioxide compound has been revealed by X‐ray structure analysis.

     

Liquid Phase Friedel‐Crafts Alkylation over Mixed Metal Oxide Catalyst

Liquid phase Friedel‐Crafts alkylation of benzene with benzyl chloride was carried out over various ferrites viz. CuFe₂O₄, NiFe₂O₄, CoFe₂O₄, ZnFe₂O₄, and MgFe₂O₄. Among the various ferrites ZnFe₂O₄ showed the highest activity. These ferrites were prepared by co‐precipitation technique. The effect of variation of catalyst, speed of agitation and reaction temperature has been studied. Benzylation of other substrates such as toluene, anisole and chlorobenzene was also studied. The catalyst ZnFe₂O₄ was found to be reusable. The acid base properties of the catalyst were studied by cyclohexanol dehydration reaction and the data was correlated with activity.     

Chiral N,N′‐Dioxide–Scandium(III) Complex‐Catalyzed Asymmetric Friedel–Crafts Alkylation Reaction of ortho‐Hydroxybenzyl Alcohols with C3‐Substituted N‐Protected Indoles

The first Lewis acid catalyzed asymmetric Friedel–Crafts alkylation reaction of ortho‐hydroxybenzyl alcohols with C3‐substituted indoles is described. A chiral N,N′‐dioxide Sc(OTf)₃ complex served not only to promote formation of ortho‐quinone methides (o‐QMs) in situ but also induced the asymmetry of the reaction. This methodology enables a novel activation of ortho‐hydroxybenzyl alcohols, thus affording the desired chiral diarylindol‐2‐ylmethanes in up to 99 % yield and 99 % ee. A range of functional groups were also tolerated under the mild reaction conditions. Moreover, this strategy gives concise access to enantioenriched indole‐fused benzoxocines.     

Aluminium Chloride‐Catalyzed Intermolecular vs Intramolecular Friedel‐Crafts Reaction of Acrylanilides and 3‐Chloropropanamides

3‐Phenylpropionanilide ( 4a ) is obtained in a yield of 89% from acrylanilide by the treatment with AlCl₃/benzene, compared with a yield of 39% by the 1,4‐conjugate addition of phenyllithium. The formation of 4a indicated that an intermolecular Friedel‐Crafts reaction occurred, rather than the relatively more facile intramolecular ring cyclization, and provided a more efficient route than a conjugate addition of phenyllithium for the preparation of 3‐phenylpropionanilide and its derivatives. Although the methoxy group is an activator of the nucleophilic substitution, introduction of a methoxy substituent at N‐phenyl did not increase the competitive capability of the intramolecular cyclization because of AlCl₃‐catalyzed demethylation to form the ArOAlCl₂ complex which decreased the availability of the π‐electron in the N‐phenyl aromatic system.     

Synthesis of Tridentate Ligands Based on Chiral Diamines and Their Application to Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes

A new type of chiral tridentate ligands were prepared and their Zn complexes were examined for the asymmetric Friedel‐Crafts alkylation of indoles with nitroalkenes, which gave rise to good yields and moderate enantioselectivities.     

ESR Studies on a Friedel‐Crafts Alkylation Reaction in [bmim]Cl‐AlCl3 Ionic Liquid

The paramagnetic complexes formed in Friedel‐Crafts alkylation reaction systems are invistigated by electron spin resonance (ESR) spectroscopy, in room temperature ionic liquids system 1‐butyl‐3‐methyl‐limidazolium chloride‐aluminium chloride ([bmim]Cl‐AlCl₃). The results indicate that ESR spectra observed are due to polycyclic aromatic radical cations formed from their parent hydrocarbons. ESR spectrum of spin adduct is obtained in an ionic liquid system composed of [bmim]Cl‐AlCl₃. In acidic solution the ¹⁴N hyperfine coupling constant of 4‐oxo‐TEMPO, 2.15 mT, is appreciably larger due to an adduct formed with AlCl₃.     

Asymmetric Friedel–Crafts Alkylation of Electron‐Rich N‐Heterocycles with Nitroalkenes Catalyzed by Diphenylamine‐Tethered Bis(oxazoline) and Bis(thiazoline) ZnII Complexes

The asymmetric Friedel–Crafts alkylation of electron‐rich N‐containing heterocycles with nitroalkenes under catalysis of diphenylamine‐tethered bis(oxazoline) and bis(thiazoline)‐Zn^II complexes was investigated. In the reaction of indole derivatives, the complex of ligand 4 f with trans‐diphenyl substitutions afforded better results than previously published ligand 4 e with cis‐diphenyl substitutions. Excellent yields (up to greater than 99 %) and enantioselectivities (up to 97 %) were achieved in most cases. The complex of ligand 4 d bearing tert‐butyl groups gave the best results in the reactions of pyrrole. Moderate to good yields (up to 91 %) and enantioselectivities (up to 91 %) were achieved in most cases. The origin of the enantioselectivity was attributed to the NH–π interaction between the catalyst and the incoming aromatic system in the transition state. Such an interaction was confirmed through comparison of the enantioselectivity and the absolute configuration of the products in the reactions catalyzed by designed ligands.     

Silica gel‐Mediated Friedel‐Crafts Reaction of Indoles with Functionalized Nitroallylic Acetates via an SN1 Process

An environmentally friendly Friedel‐Crafts reaction was demonstrated between indoles and functionalized nitroallylic acetates in the presence of silica gel, providing the corresponding C‐3‐selective regioisomers in good to high overall chemical yields (70‐93%).     

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.     

三氟甲磺酸镱催化吲哚与硝基烯Friedel-Crafts反应的研究

用三氟甲磺酸镱和配体共同催化吲哚与β-硝基烯的Friedel-Crafts反应,从而发展了一条简捷新颖地合成天然产物中广泛存在的3-取代吲哚衍生物的方法.该催化剂有反应条件温和、操作简单和价格较低等优点.