Enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes catalyzed by a bis(oxazoline)-Cu(II) complex

The catalytic enantioselective Friedel-Crafts reaction of indole with trans-β-nitrostyrene is reported in the presence of copper triflate-bisoxazoline complexes. The reaction furnished nitroalkylated indoles in excellent yields (up to 95%) and high enantioselectivities up to an 86% ee.     

Asymmetric Friedel-Crafts alkylation of methoxyfuran with nitroalkenes catalyzed by diphenylamine-tethered bis(oxazoline)-Zn(II) complexes

The first catalytic asymmetric Friedel-Crafts reaction of 2-methoxyfuran with nitroalkenes was developed under the catalysis of diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complexes. The reaction conditions and ligands were optimized, and the scope of the reaction was tested by varying the nitroalkenes. For most of aromatic and heteroaromatic nitroalkenes, good yields and high enantioselectivities (86-96% ee) were obtained. The methoxyfuran group in the product can be transformed to carboxylic acid via oxidative fragmentation with full retention of the configuration.     

Enantioselective Friedel-Crafts alkylation of indoles with 2-enoylpyridine-N-oxides catalyzed by glucoBOX-Cu(II) complex

The glucosamine derived glucoBOX-Cu(II) complex was found to be a unique catalytic system for enantioselective Friedel-Crafts alkylation of indoles with 2-enoylpyridine-1-oxides. A large number of 3-alkylated indole derivatives were prepared using 5 mol% glucoBOX-Cu(II) complex in excellent yields with high enantioselectivity up to 99% ee.     

Asymmetric Friedel-Crafts alkylation of indoles with 3-nitro-2H-chromenes catalyzed by diphenylamine-linked bis(oxazoline) and bis(thiazoline) Zn(II) complexes

An efficient diastereo- and enantioselective Friedel-Crafts alkylation of indoles with 3-nitro-2H-chromenes catalyzed by diphenylamine-linked bis(oxazoline) and bis(thiazoline) Zn(II) complexes has been developed. This asymmetric Friedel-Crafts alkylation led to medicinally privileged indolyl(nitro)chromans in good yields with high enantioselectivities (up to 95% ee) and diastereoselectivities under mild reaction conditions.     

Asymmetric Friedel-Crafts alkylations of indoles with nitroalkenes catalyzed by Zn(II)-bisoxazoline complexes

[reaction: see text] A novel asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes catalyzed by Zn(II)-bisoxazoline complexes has been developed. The nitroalkylated indoles are synthesized in excellent yields and high enantioselectivities (up to 90% ee). The effects of ligand structure, metal salt, and solvent on the reaction are discussed. The substrates of the reaction can be aromatic, heteroaromatic, and even aliphatic nitroalkenes. The high reactivity and selectivity of the reaction are presumptively attributed to the activation and asymmetric induction of chiral Lewis acids coordinated by nitroalkene substrates through a 1,3-metal bonding model.     

Enantioselective Friedel-Crafts reaction of indoles with carbonyl compounds catalyzed by bifunctional cinchona alkaloids

In this communication, we report an efficient asymmetric Friedel-Crafts reaction that, unprecedently, is applicable to a wide range of both indoles and carbonyls. The use of a readily accessible catalyst in combination with a high enantioselectivity that is insensitive to reaction concentration, temperature, air, and moisture should allow this reaction to provide useful enantioselective access to new chiral indole derivatives. [reaction: see text]     

Asymmetric Michael addition of nitroalkanes to nitroalkenes catalyzed by C2-symmetric tridentate bis(oxazoline) and bis(thiazoline) zinc complexes

The first asymmetric synthesis of 1,3-dinitro compounds through Michael addition of nitroalkanes to nitroalkenes catalyzed by C2-symmetric chiral tridentate bis(oxazoline) and bis(thiazoline) zinc complexes was achieved with high enantioselectivities (up to 95% ee).     

Friedel-Crafts alkylation of indoles with epoxides catalyzed by nanocrystalline titanium(IV) oxide

Friedel-Crafts alkylation of indoles with epoxides to afford 3-alkyl indole derivatives at room temperature with moderate to good yields and high regioselectivity using nanocrystalline titanium(IV) oxide catalyst is described.     

Enantioselective Friedel-Crafts alkylation of indoles with trifluoroethylidene malonates by copper-bis(oxazoline) complexes: construction of trifluoromethyl-substituted stereogenic tertiary carbon center

An enantioselective alkylation of indoles with trifluoroethylidene malonates catalyzed by copper(II)-bis (oxazoline) complexes has been developed. The expected adducts with a stereogenic tertiary carbon center bearing a trifluoromethyl group were obtained in excellent yields (up to 99%) and ee values (up to 96% ee). The synthetic utility of this asymmetric catalytic reaction was demonstrated by the preparation of β-CF(3)-tryptophan and 4-CF(3)-β-carboline in high ee.     

Enantioselective Friedel-Crafts alkylation reactions catalyzed by a chiral nonracemic C2-symmetric 2,2'-bipyridyl copper(II) complex

Enantioselective Friedel-Crafts alkylation reactions of a series of substituted indoles with methyl trifluoropyruvate, catalyzed by a chiral nonracemic C(2)-symmetric 2,2'-bipyridyl copper(II) triflate complex, are described. The corresponding 3,3,3-trifluoro-2-hydroxy-2-indole-3-yl-propionic acid methyl esters were formed in good yield and in high enantiomeric excess (up to 90%). This is the first report of the use of a chiral nonracemic 2,2'-bipyridyl ligand in catalytic and enantioselective Friedel-Crafts alkylation reactions. The structural characterization of a copper(II) chloride complex of the chiral 2,2'-bipyridyl ligand by X-ray crystallography is also presented. [reaction: see text]     

Enantioselective and diastereoselective Mukaiyama-Michael reactions catalyzed by bis(oxazoline) copper(II) complexes.

The scope of highly enantioselective and diastereoselective Michael additions of enolsilanes to unsaturated imide derivatives has been developed with use of [Cu((S,S)-t-Bu-box)](SbF6)2 (1a) as a Lewis acid catalyst. The products of these additions are useful synthons that contain termini capable of differentiation under mild conditions. Michael acceptor pi-facial selectivity is consistent with two-point binding of the imide substrate and can be viewed as an extension of substrate enantioselection in the corresponding Diels-Alder reactions. A model analogous to the one employed to describe the hetero Diels-Alder reaction is proposed to account for the observed relation between enolsilane geometry and product absolute diastereocontrol. Insights into modes of catalyst inactivation are given, including spectroscopic evidence for inhibition of the catalyst by a dihydropyran intermediate that evolves during the course of the reaction. A procedure is disclosed in which an alcohol additive is used to hydrolyze the inhibiting dihydropyran and afford the desilylated Michael adduct in significantly shortened reaction time.     

Enantioselective Friedel-Crafts reaction of indoles with arylidene malonates catalyzed by iPr-bisoxazoline-Cu(OTf)2

The cheap and simple (i)Pr-bisoxazoline-Cu(OTf)(2) proves to be an efficient catalyst in the asymmetric Friedel-Crafts reaction of indole with arylidene malonates. In (i)BuOH, the S-enantiomer was obtained in up to 97% ee, while the opposite enantiomer was obtained in up to 78% ee in CH(2)Cl(2) or TTCE.     

Highly enantioselective Friedel-Crafts alkylations of pyrroles and indoles with alpha'-hydroxy enones under Cu(II)-simple bis(oxazoline) catalysis

Remarkably high and regular enantioselectivities are obtained in Friedel-Crafts alkylation reactions involving alpha'-hydroxy enone templates and Cu(II)-bis(oxazoline) complexes as catalysts. The simple elaboration of adducts provides a route to enantioenriched aldehydes, carboxylic acids, and ketones containing the pyrrole and indole frameworks.     

A new type of bis(sulfonamide)-diamine ligand for a Cu(OTf)2-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with nitroalkenes

Chiral bis(sulfonamide)-diamine served as new type of ligand for a Cu(OTf)(2)-catalyzed asymmetric Friedel-Crafts alkylation reaction of indoles with nitroalkenes. The desired products were obtained with up to 99% yield and 97% ee.     

Enantioselective Friedel-Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

The enantioselective Friedel-Crafts addition of a variety of indoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes (Sc(III)-pybox) was accomplished utilizing a series of beta-substituted alpha,beta-unsaturated phosphonates and alpha,beta-unsaturated 2-acyl imidazoles. The acyl phosphonate products were efficiently transformed into esters and amides, whereas the acyl imidazole adducts were converted to a broader spectrum of functionalities such as esters, amides, carboxylic acids, ketones, and aldehydes. The sense of stereoinduction and level of enantioselectivity were found to be functions of the size of the substrate employed, the substitution on the ligand, and the catalyst loading. Molecular modeling of the catalyst with the bound substrates was performed based on the crystal structures of the catalyst complexes and the sense of stereoinduction observed in the addition reaction. Nonlinear effects over a range of catalyst concentrations implicate a mononuclear complex as the active catalyst.     

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.     

Enantioselective Michael addition of anthrone to nitroalkenes catalyzed by bifunctional thiourea-tertiary amines

A highly bifunctional thiourea-tertiary amine-catalyzed enantioselective Michael addition reaction of anthrone to a wide variety of nitroalkenes has been developed, and the corresponding adducts were obtained smoothly in high yields (up to 97%) and good enantioselectivities (up to 94% ee).