Friedel-Crafts alkylation of indoles

The alkylation of indole and 2-methylindole with alkyl halides in the presence of a complex catalyst — dipyridinezinc chloride — was investigated. Nitromethane was used as the solvent. 3-Alkylindoles were obtained in 30–80% yields in all cases. The reaction mechanism is discussed. Data from the PMR and mass spectra are presented.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 921–924, July, 1978.     

Enantioselective synthesis of fluorene derivatives by chiral N-triflyl phosphoramide catalyzed double Friedel-Crafts alkylation reaction

A highly efficient tandem double Friedel-Crafts reaction between indoles and 2-formylbiphenyl derivatives by chiral N-triflyl phosphoramide was realized. Under mild conditions, various 9-(3-indolyl) fluorene derivatives have been obtained in good yield and up to 94% ee. Comparing to their corresponding chiral phosphoric acids, chiral N-triflyl phosphoramides catalyzed reactions led to products with opposite absolute configuration.     

Diastereoselective Friedel-Crafts alkylation of hydronaphthalenes

An efficient and versatile synthesis of chiral tetralins has been developed using both inter- and intramolecular Friedel-Crafts alkylation as a key step. The readily available hydronaphthalene substrates were prepared via a highly enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes followed by hydrogenation. A wide variety of complex tetracyclic compounds have been isolated with high levels of regio-, diastereo-, and enantioselectivity.     

阴离子相转移催化的Friedel-Crafts烷基化反应

提出三种阴离子表面活性剂十二烷基苯磺酸钠、十二烷基磺酸钠、十二烷基硫酸钠作为阴离子相转移催化剂特性。研究了它们在Friedel-Crafts反应中的催化性能,结果表明它们都有良好的催化特性合成了七个化合物, 其中五个为未见文献报导的新化合物, 它们是二苯甲基萘酚和二苯甲基酚类化合物。     

Exploring a chemical encoding strategy for combinatorial synthesis using Friedel-Crafts alkylation

The use of scandium(III) triflate and ytterbium(III) triflate-catalysed Friedel-Crafts alkylation to insert a set of hydroxymethyl pyrrole amide tags (1b-i) on to polystyrene resins under mild conditions and the encoding of a split and mix peptide library is demonstrated.     

Diastereoselective intramolecular Friedel-Crafts alkylation of tetralins

An efficient and versatile synthesis of cis-hexahydrobenzophenanthridines starting from readily available tetralins has been developed using an intramolecular Friedel-Crafts alkylation as a key step. The substrates were prepared via a highly stereocontrolled rhodium-catalyzed ring-opening reaction of meso-oxabicyclic alkenes and a hydrogenation sequence. Thus, a wide variety of complex tetracyclic compounds have been isolated with a high level of regio-, diastereo-, and enantioselectivity.     

Microwave accelerated facile synthesis of fused polynuclear hydrocarbons in dry media by intramolecular Friedel-Crafts alkylation

Fused polynuclear tetrahydro arenes are synthesised in a fast, simple, high yielding and regiospecific procedure by an intramolecular Friedel-Crafts alkylation in dry media under microwave irradiation of the corresponding 1-bromo-4-arylbutanes immobilised on silica. The observed reactivity is rationalised by molecular modelling studies which suggest the occurrence of a concerted mechanism.     

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.     

Microwave-assisted silica-supported aluminum chloride-catalyzed Friedel-Crafts alkylation

Microwave irradiation is a popular method in organic synthesis to achieve high yields in shorter reaction times. This decreases total ‘man-hours’ in a synthetic setting. Another technique used in organic chemistry to decrease manual manipulations, is solid support reagents. The benefits of this approach is that upon completion of a reaction, a simple filtration can be performed which expedites the work-up and also produces less organic waste. Friedel-Crafts alkylation has been explored using microwave chemistry as well as with solid-supported reagents. In comparison with traditional heating, as well as with AlCl₃, superior yields were observed with silica-gel bound aluminum chloride (Si-AlCl_x) when microwave irradiated for only 5 min.     

Highly efficient synthesis of polysubstituted fluorene via iron-catalyzed intramolecular Friedel-Crafts alkylation of biaryl alcohols

An efficient and mild Fe(III)-catalyzed intramolecular Friedel-Crafts alkylation of biaryl methanol derivatives has been developed to achieve the substituted fluorene derivatives. The present reaction provides an excellent alternative to published methods because of its high yields, operational simplicity, mild conditions, and use of inexpensive and sustainable catalyst.     

Samarium triflate-catalyzed halogen-promoted Friedel-Crafts alkylation with alkenes

A versatile and efficient halogen-promoted highly regio- and stereoselective Friedel-Crafts (F-C) alkylation with alkenes has been developed with use of easily available and inexpensive NBS or I2 as the efficient halogen sources. Lewis acids, in particular metal triflates, are found to be effective catalysts for this halogen-promoted F-C alkylation. Among these, Sm(OTf)3 was the best catalyst. Electron-rich arenes smoothly underwent F-C alkylation with a variety of alkenes including alpha,beta-unsaturated carbonyl compounds.     

Asymmetric synthesis of chiral 9,10-dihydrophenanthrenes using Pd-catalyzed asymmetric intramolecular Friedel-Crafts allylic alkylation of phenols

We developed a novel asymmetric synthetic method for multisubstituted 9,10-dihydrophenanthrenes based on the Pd-catalyzed asymmetric intramolecular Friedel-Crafts allylic alkylation of phenols, which produces 10-vinyl or 10-isopropenyl chiral 9,10-dihydrophenanthrene derivatives in high yield with up to 94% ee.     

Highly enantioselective Friedel-Crafts alkylation reaction catalyzed by rosin-derived tertiary amine-thiourea: synthesis of modified chromanes with anticancer potency

We present herein for the first time the synthesis and preliminary biological evaluation of various modified chromanes via a rosin-derived tertiary amine-thiourea-catalyzed highly enantioselective Friedel-Crafts alkylation reaction.     

Iodine-catalyzed Friedel-Crafts alkylation of electron-rich arenes with aldehydes: efficient synthesis of triarylmethanes and diarylalkanes

Iodine is shown to be an efficient catalyst for the Friedel-Crafts alkylation of arenes with a wide variety of aldehydes in toluene under ‘open-flask’ and mild conditions. In the presence of 10 mol % of iodine, the reaction of arenes with aromatic aldehydes gives the corresponding triarylmethane derivatives (TRAMs), regioselectively, in good to excellent yields. On the other hand, a series of diarylalkane derivatives is synthesized smoothly by the reaction with aliphatic aldehydes.     

A cycloisomerization/Friedel-Crafts alkylation strategy for the synthesis of pyrano[3,4-b]indoles

The synthesis of pyrano[3,4-b]indoles is described. The reaction sequence involves Sonogashira coupling of dihydropyran propargyl ether scaffolds with iodoanilines to afford intermediate indoles. Lewis acid-catalyzed ionization of the dihydropyrans, followed by intramolecular C3 alkylation of the indole, provides the title compounds.     

Naphthalene-based calixarenes: unusual regiochemistry of a Friedel-Crafts alkylation

[reaction: see text] In the pursuit of naphthalene-based calixarenes, a Friedel-Crafts alkylation with unusual regiochemistry was observed. Treatment of carbinol 14 with catalytic triflic acid was expected to produce calixarenes of the class represented by 16. Instead, the major product was cyclic trimer 15, in which alkylation of each naphthalene ring occurred at the electronically deactivated position. The structure of compound 15 was assigned by 2-D NMR studies.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

Organocatalytic enantioselective Friedel-Crafts alkylation of simple phenols with trifluoropyruvate

Enantioselective Friedel-Crafts alkylation of simple phenols (4a-j) with 3,3,3-trifluoropyruvate (3) was accomplished by using chiral cinchona alkaloid catalyst 2h (10 mol %). High yields and enantioselectivities (71-94% ee) of the Friedel-Crafts alkylation products were obtained.     

TFA-mediated tandem Friedel-Crafts alkylation/cyclization/hydrogen transfer process for the synthesis of flavylium compounds

The tandem reaction of phenols and chalcones in refluxing TFA gave the flavylium species of 2-hydroxy-2-phenyl-2H-chromenes in moderate to good isolated yields. The reaction was proposed to involve a tandem transformation of Friedel-Crafts alkylation, dehydrative cyclization, intermolecular hydrogen transfer, and hydration. As a multifunctional catalyst, TFA mediated the processes efficiently and cleanly.