Lewis acid-catalyzed Friedel-Crafts acylation reaction using carboxylic acids as acylating agents

Rare-earth metal Lewis acids, in particular Eu(NTf₂)₃, were found to be efficient catalysts for Friedel-Crafts acylation reaction using aliphatic as well as aromatic carboxylic acids as acylating agents at high temperature.     

Synthesis of 1-indanones by intramolecular Friedel-Crafts reaction of 3-arylpropionic acids catalyzed by Tb(OTf)3

Intramolecular Friedel-Crafts acylation reaction of 3-arylpropionic acids was efficiently catalyzed by Tb(OTf)₃ at 250 °C to give 1-indanones. Even deactivated 3-arylpropionic acids with halogen atoms on the aromatic ring can be cyclized in moderation to good yields.     

Convenient Synthesis of Indene Derivatives via Intramolecular Friedel-Crafts Cyclization of Tetraaryl Substituted 1,3-Butadienes

A convenient and efficient method for the highly regioselecfive synthesis of indene derivatives 4 and 5 from tetraaryl substituted 1,3-butadienes 3 was described. The method involves an intramolecular Friedel-Crafts cyclization and a corresponding double-bond positional shift of isomers 4 and 5 in the presence of different Lewis acids under mild conditions with higher than 90% yields.     

Facile N-formylation of amines using Lewis acids as novel catalysts

Alky, aryl, and heteroaryl amines were found to react efficiently with formic acid under Lewis acid catalysis giving N-formyl derivatives in high yields. A study of ZnCl₂-catalyzed N-formylation of a variety of amines using formic acid as formylating agent is described.     

分子内Friedel-Crafts环化反应在苯并环状物合成中的应用

Friedel-Crafts反应是有机合成中最有用的反应之一,它的应用范围十分广泛.Friedel-Crafts反应也是合成环状化合物的重要途径,尤其分子内的环化反应一直以来受到广泛的关注.对近年来应用分子内Friedel-Crafts环化反应合成苯并环状化合物进行了详细的综述,并对分子内Friedel-Crafts环化反应在有机合成上发展前景作了展望.     

Triflic acid-catalyzed cascade cyclization of arenyl enynes via acetylene-cation cyclization and Friedel-Crafts type reaction

A novel triflic acid-catalyzed cascade cyclization of arenyl 1,7-enynes through acetylene-cation cyclization followed by Friedel-Crafts reaction has been described. Various fused poly carbocycles can be obtained in good to high yields under mild reaction conditions.     

Development of efficient Lewis acid catalysts for intramolecular cycloaddition reactions of ester-tethered substrates

We have developed novel bidentate Lewis acids that efficiently promote the intramolecular cycloaddition reactions of ester-tethered substrates. Bis-aluminated triflic amide derivatives [TfN(AlR(1)R(2))2], which are generated by simply mixing triflic amide and 2 equiv of methyl aluminum or aluminum hydride, catalyzed intramolecular Diels-Alder (DA) reactions of ester-tethered 1,7,9-trienes and intermolecular DA reactions of alpha,beta-unsaturated lactones. We also found that bimetallic Lewis acid derived from 1,1'-biphenyl-2,2'-di(triflyl)amide and dimethylaluminum chloride promoted the intramolecular [3 + 2] cycloaddition reaction of acrylate derivatives having an allylsilane part.     

An efficient synthesis of chiral isoquinuclidines by Diels-Alder reaction using Lewis acid catalyst

The Diels-Alder reaction of 1,2-dihydropyridine derivatives (1-phenoxycarbonyl-1,2-dihydropyridine 1 or 1-methoxycarbonyl-1,2-dihydropyridine 4) with N-acryloyl (1S)-2,10-camphorsultam (1S)-2 {or N-acryloyl (1R)-2,10-camphorsultam (1R)-2} in the presence of Lewis acid, such as titanium tetrachloride, zirconium tetrachloride, and hafnium tetrachloride afforded the endo-cycloaddition product, 2-azabicyclo[2.2.2]octane derivatives in good yields with excellent diastereoselectivity. The absolute stereochemistry assignment of the endo-cycloaddition product (1S)-5a starting from N-acryloyl (1S)-2,10-camphorsultam (1S)-2 has been established to be (1S,4R,7S) and the reaction mechanism was proposed.     

Highly stereoselective Friedel-Crafts type cyclization. Facile access to enantiopure 1,4-dihydro-4-phenyl isoquinolinones

The present report describes a stereoselective synthesis of 1,4-dihydro-4-phenyl isoquinolinones 5 based on a stereoselective Friedel-Crafts type cyclization. Cyclization precursors 1 were prepared in two steps, from the readily available (S)-mandelic acid, in 60-80% overall yield. The stereoselective electrophilic cyclization was accomplished in 20-86% yield and with 20-97% ee. In the course of this work, the presence of the amide carbonyl was found to be particularly important to guarantee a stereospecific process during the electrophilic aromatic substitution.     

Friedel-Crafts alkylation of indoles with trichloroacetimidates

Substituted indole scaffolds are often utilized in medicinal chemistry as they regularly possess significant pharmacological activity. Therefore the development of simple, inexpensive and efficient methods for alkylating the indole heterocycle continues to be an active research area. Reported are reactions of trichloroacetimidate electrophiles and indoles to address the challenges of accessing alkyl decorated indole structures. These alkylations perform best when either the indole or the imidate is functionalized with electron withdrawing groups to avoid polyalkylation.     

TFA-mediated intramolecular Friedel-Crafts reaction. An efficient metal and halogen free route to stereoselective synthesis of benzocycles

6-Acetoxy-4-alkenyl arenes undergo regio- and stereoselective intramolecular Friedel-Crafts reaction affording benzocycles in moderate to excellent yields in TFA/HOAc (3:1). It was observed that introduction of alkyls or phenyl group to the allylic acetate moiety facilitates the cyclization reaction. The optically active tricyclic (4bR,8aS)-4b,7,8,8a,9,10-hexahydrophenanthrene skeleton could also be easily obtained in excellent yields.     

A novel reaction of titanacyclopentenes and aldehydes with or without Lewis acids

Oxatitanacyclopentenes were prepared in high yields from the reaction of aldehydes with titanacyclopenetens via substitution of ethylene. No insertion product was obtained in this reaction. The combination of alkynes and aldehydes played an important role in the successive formation of oxatitanacyclopentenes. Some oxatitanacyclopentenes are very stable and can be purified using column chromatography. The cooperation between Ti and LA led to very different results from that between Zr and LA.     

Highly efficient synthesis of functionalized dihydronaphthalenes, tetrahydronaphthalenes, and tetrahydroisoquinolines by iron-catalyzed intramolecular Friedel-Crafts reaction of aryl-containing propargylic alcohols

An efficient, convenient, and one-pot procedure for the synthesis of a series of new dihydro- and tetrahydronaphthalenes as well as tetrahydroisoquinolines has been established through Lewis acid-catalyzed intramolecular Friedel-Crafts reaction of aryl-substituted propargylic alcohols.     

Synthesis of indenes by ytterbium-catalyzed carboalkoxylation/Friedel-Crafts reaction of arylidenecyclopropanes with acetals

Ytterbium-catalyzed tandem carboalkoxylation/Friedel-Crafts reaction of arylidenecyclopropanes 1 with acetals 2 afforded the corresponding indene derivatives 3 in good to high yields. For example, in the presence of 10 mol % of Yb(OTf)₃ the reaction of 1-phenylbenzylidenecyclopropane 1a with the dimethyl acetals of benzaldehyde 2a, p-tolualdehyde 2b, and p-anisaldehyde 2c gave 1,3-diphenyl-2-(2-methoxyethyl)indene 3a, 2-(2-methoxyethyl)-3-phenyl-1-(p-tolyl)indene 3b, and 1-(p-anisyl)-2-(2-methoxyethyl)-3-phenylindene 3c in 82%, 80%, and 80% yields, respectively.     

Fluorous reverse-phase silica gel-supported Lewis acids as recyclable catalysts in water

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids which have fluorous ligands acted as effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. Direct esterification of carboxylic acid with alcohol in organic media was also catalyzed. The FRPSG-supported Lewis acids could be recycled by simple filtration after the reaction.     

Lewis and Brönsted acid catalyzed Friedel-Crafts hydroxyalkylation of mucohalic acids: a facile synthesis of functionalized γ-aryl γ-butenolides

A catalytic, green and practical method for Friedel-Crafts hydroxyalkylation of mucohalic acid has been accomplished. Reaction of mucohalic acids with various electron-rich aromatic compounds in the presence of catalytic (1 mol % to 10 mol %) In(OTf)₃ or Brönsted acid, such as H₂SO₄ in acetic acid provides γ-aryl γ-butenolides in moderate to excellent yield.     

TiCl4-promoted intramolecular cyclization of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones: an expedient method to prepare 2-tetralones

DABCO is a very effective catalyst in the formation of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones 12 from the corresponding α-carbonatoaldehyde. Intramolecular cyclization of cyclic carbonates 12 promoted by TiCl₄ affords 2-tetralones 13 containing a variety of substituents in high yields.     

Assessment of fluoroalkyltin compounds as fluorous Lewis acid catalysts

The synthesis of a variety of organotin compounds with 1H, 1H, 2H, 2H‐perfluorooctyl groups is reported, together with an improved method for the corresponding distannoxane. Unique properties of this compound are disclosed in terms of fluorophilicity and activity as a Lewis acid catalyst in comparison with other mono‐nuclear derivatives. A new criterion for obtaining high solubility in fluorocarbon solvents is presented. Copyright © 2003 John Wiley & Sons, Ltd.     

A simple Lewis acid induced reaction of phenols with electrophiles: Synthesis of functionalized 4H-chromenes and ortho-benzylphenols

Abstract

Lewis acid ZnCl₂ promoted cyclization protocol to 4H-chromenes is accomplished, using readily available phenols and acetophenones as starting materials. Interestingly, the process is feasible under the solvent free environment. Synthesis of a variety of 4H-chromenes have been accomplished using this strategy. In addition, this concept is extended to the synthesis of ortho-benzylphenols by treating phenols either with styrenes or secondary benzylic alcohols.