Modification of diphenylamine-linked bis(oxazoline) ligands: Tuning of electronic effect and rigidity of ligand skeleton

The electronic effect of diphenylamine-linked bis(oxazoline) ligands was tuned through introduction of electron-withdrawing bromo and nitro substituents onto the 4 and 4′ position. The variation of the NH bond acidity was determined by the different chemical shifts of NH. The catalytic activity and enantioselectivity of the modified ligands were tested in the asymmetric Friedel-Crafts alkylation of indole with β-nitrostyrene. The effect of ligand skeleton rigidity was also investigated through the synthesis of iminodibenzyl-linked bis(oxazoline) ligands and evaluation of their catalytic activity in Friedel-Crafts alkylation.     

Enantioselective Friedel-Crafts alkylations of alpha,beta-unsaturated 2-acyl imidazoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes

An enantioselective Friedel-Crafts alkylation with alpha,beta-unsaturated 2-acyl imidazoles and electron-rich aromatic nucleophiles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes has been accomplished. These alpha,beta-unsaturated 2-acyl imidazoles are effective electrophiles for the Friedel-Crafts reaction. The resulting adduct 2-acyl imidazole is easily converted to amides, esters, carboxylic acids, ketones, and aldehydes by methylation and subsequent displacement of the imidazole residue.     

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

A highly enantioselective Friedel-Crafts alkylation of electron-rich aromatic nucleophiles catalyzed by scandium(III) triflate-pyridyl(bis)oxazoline complexes has been accomplished. The reaction involves alpha,beta-unsaturated acyl phosphonates as electrophiles and primarily substituted indoles as nucleophiles. The reactive acyl phosphonate product is converted to the corresponding ester or amide in good overall yield by adding an alcohol or amine directly to the reaction mixture.     

Enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes catalyzed by bifunctional tridentate bis(oxazoline)-Zn(II) complex

[reaction: see text] A more practical and efficient catalytic asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes using bifunctional tridentate bis(oxazoline)-Zn(OTf)(2) as catalyst has been developed. Various types of the nitroalkylated indoles were obtained in excellent yields (85-99%) and high enantioselectivities (up to 98% ee).     

Synthesis of highly modular bis(oxazoline) ligands by Suzuki cross-coupling and evaluation as catalytic ligands

New bis(oxazoline) ligands (BOXs) containing biaryl substitutents at the C-4 position and H or CH₂OR substituents at the C-5 position have been synthesized using Suzuki cross-coupling as the main tool for structural diversity. Copper, zinc, and palladium complexes of the prepared BOXs have been evaluated in the following catalytic asymmetric processes: Acylation with kinetic resolution of trans-1,2-cyclohexanediol (Cu), enantioselective Friedel-Crafts alkylation of indole (Zn), and enantioselective alkylation of 3-acetoxy-1,3-diphenylpropene (Pd).     

An improved synthesis of bis(cyclopentadienone)

<正>An improved strategy for the synthesis of 3,3'-(oxy-p-phenylene)bis(2,4,5-triphenylcyclopentadienone) was developed,which includes three steps:Friedel-Crafts reaction,oxidation and condensation.Importantly,the use of KMnO_4 made the second step simple and efficient,which has potential application to synthesis of bis(cyclopentadienone)s.The course of oxidation has been confirmed by isolated intermediates.     

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.     

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.     

Bis heterocycles as potential chemotherapeutic agents. X. Synthesis of bis(4-arylthiosemicarbazido)-, bis(2-arylamino-1,3,4-thiadiazol-5-yl) and bis(4-aryl-1,2,4-triazolin-3-thione-5-yl)pentanes and related compounds

Synthesis of several bis(4-arylthiosemicarbazido- 1 , bis(2-arylamino-1,3,4-thiadiazol-5-yl)- 5 and bis(4-aryl-1,2,4-triazolin-3-thione-5-yl)- 2 pentanes is described. Sulphides 3 and sulphones 4 are also prepared from 2 by alkylation and subsequent oxidation with hydrogen peroxide respectively.     

Enantiopure fluorous bis(oxazolines): synthesis and applications in catalytic asymmetric reactions

Various enantiopure fluorous bis(oxazolines) with fluorine content between 52.7 and 58.7% have been synthesized by a simple reaction sequence that involved the introduction of two fluorinated ponytails by alkylation of the corresponding nonfluorous bis(oxazolines). These new ligands have been used in palladium-catalyzed alkylation of rac-(E)-1,3-diphenylpropenyl acetate with carbon nucleophiles and in copper-catalyzed oxidation of cycloalkenes; these ligands exhibited enantioselectivities up to 98 and 77%, respectively, quite close to the values obtained using the analogous nonfluorous bis(oxazolines). These ligands could be easily recovered by liquid-liquid extraction or solid-liquid separation and reused with the same enantioselectivities.     

Catalytic enantioselective Friedel-Crafts alkylations of indoles with alpha'-phosphoric enones

The C2-symmetric bis(oxazoline) copper(II) complex proves to be an excellent catalyst in the Friedel-Crafts alkylation of indoles with alpha'-phosphoric enones. The enantioselectivities of this reaction are obtained in up to 98% ee.     

Square planar bis(imino)pyridine iron halide and alkyl complexes

Square planar iron methyl complexes containing bis(imino)pyridine (PDI) ligands have been prepared by reductive alkylation of the corresponding ferrous dichloride; dialkylation is observed upon treatment with a larger alkyl lithium.     

Carbon nucleophiles in the Mitsunobu reaction. Mono- and dialkylation of bis(2,2,2-trifluoroethyl) malonates

[formula: see text] Simple dialkyl malonate esters, for example diethyl malonate, exhibit relatively limited scope as carbon nucleophiles in the Mitsunobu dehydrative alkylation reaction. In contrast, bis(2,2,2-trifluoroethyl) malonate readily undergoes dehydrative alkylation with primary alcohols, and using only a slight excess of malonate gives monoalkylated product in good yield. Some secondary alcohols can also be employed, and bis(2,2,2-trifluoroethyl) malonates can be used in a second dehydrative alkylation to give dialkylated products in good to excellent yield.     

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.     

The synthesis of phosphine oxide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation

The phosphine oxide-linked bis(oxazoline) ligands were designed and synthesized in two ways. One is the coupling of Grignard reagent derived from 2-(2-bromophenyl)oxazoline with phenylphosphonic dichloride, another route is the condensation of bis(2-formylphenyl)(phenyl)phosphine oxide with chiral amino alcohols followed by NBS oxidation. These new bis(oxazoline) ligands were applied in Pd-catalyzed asymmetric allylic alkylation reactions and good yields and enantioselectivities were obtained with diphenyl substituted ligand (up to 95% ee).     

Synthesis of new C2- symmetric fluoren-9-ylidene malonate derived bis(oxazoline) ligands and their application in Friedel-Crafts reactions

A series of new C(2)-symmetric fluoren-9-ylidene malonate-derived bis(oxazoline) ligands were synthesized from fluoren-9-ylidene malonate and enantiomerically pure amino alcohols via a convenient route. Their asymmetric catalytic properties in the Friedel-Crafts reactions of indoles with arylidene malonates were evaluated, and the Cu(OTf)2 complex of a fluoren-9-ylidene malonate-derived bis(oxazoline) bearing a phenyl group showed moderate to good enantioselectivity (up to 88% ee).     

Silver-promoted Friedel-Crafts reaction: concise total synthesis of (-)-ardeemin, (-)-acetylardeemin and (-)-formylardeemin

Total syntheses of multidrug resistant inhibitors (-)-acetylardeemin 2a, (-)-ardeemin 2b, and (-)-formylardeemin 3 have been achieved within 10 steps starting from bromopyrroloinoline 13. The key step involves direct alkylation of 13 with prenyl tributylstannane 11 to yield 12 via a silver-promoted asymmetric Friedel-Crafts reaction. Highly efficient installation of the isoprenyl group allowed excellent overall yield. Moreover, the substrate scope of the asymmetric Friedel-Crafts reaction of 13 was expanded to include a variety of arenes 14 to afford natural product-like library analogues 15.     

Double dearomatization of bis(diphenylphosphinamides) through anionic cyclization. A facile route of accessing multifunctional systems with antitumor properties

The sequential one-pot double dearomatization of bis(N-benzyl-P,P-diphenylphosphinamides) via anionic cyclization is described for the first time. Protonation and alkylation of the dearomatized dianions provide bis(tetrahydro-2,1-benzazaphospholes) in good yield and with very high regio- and stereocontrol. Acid-catalyzed methanolysis of the bisheterocycles affords bis(methyl gamma-aminophosphinates) stereospecifically. The doubly phosphorylated systems proved to be active against a series of cancer cell lines.     

Metal bis(perfluorooctanesulfonyl)amides as highly efficient Lewis acid catalysts for fluorous biphase organic reactions

In fluorous biphase system, metal bis(perfluorooctanesulfonyl)amides are better Lewis acid catalysts than the analogous triflates toward either transesterifications, or direct esterifications, or Friedel-Crafts acylations or Baeyer-Villiger oxidations. These catalysts are selectively soluble in lower fluorous phase and can be recovered simply by phase separation. Furthermore, these catalysts can be reused without decrease of activity in most cases.