VAPOL phosphoric acid catalysis: the highly enantioselective addition of imides to imines

The first highly enantioselective catalytic method for the preparation of chiral aminals via the addition of imide nucleophiles to imines is reported.     

The highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids

The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported. In general, derivatives of substituted 3-amino-2-oxindoles were obtained with excellent enantioselectivities and high yields.     

Chiral phosphoric acid-catalyzed addition of thiols to N-acyl imines: access to chiral N,S-acetals

The first catalytic asymmetric method to prepare enantioenriched N,S-acetals using chiral BINOL phosphoric acids is reported. The reaction combines N-acyl imines with thiols to generate products in excellent yield and enantioselectivity. The addition reaction could also be achieved with an exceptional substrate to catalyst (S/C) molar ratio. Electron-rich and electron-deficient aromatic N-acyl imines, as well as a broad range of aliphatic and aromatic thiols, showed excellent reactivity.     

Evaluation of chiral oxazolines for the highly enantioselective diethylzinc addition to N-(diphenylphosphinoyl) imines

On the basis of the principle that the incorporation of the structurally rigid and conformationally restricted skeleton in beta-amino alcohols is beneficial to the enantioselective diethylzinc addition to imines, a series of chiral oxazolines, which had been designed and conveniently prepared from commercially available (1S,2S)-2-amino-1-phenylpropane-1,3-diol, were applied in the diethylzinc addition to diphenylphosphinoyl imines to give high yields of 68-84% and excellent ee values of 90-95%. The configuration of the product was controlled by the chirality of the carbon bonded to the hydroxyl group in the oxazoline. Oxazolines bearing a para- or meta-substituted phenyl group generally offered higher enantioselectivity than those containing an ortho-substituted phenyl. The X-ray structures of 4f and 4j, in combination with the proposed transition state, preliminarily explained why oxazolines with a para- or meta-substituent on the phenyl group gave higher enantioselectivities than those bearing an ortho-substituent. This successful example using chiral oxazolines to promote the titled reaction implies that a large family of chiral compounds containing an oxazoline ring moiety have the potential to be developed for promoting the highly enantioselective dialkylzinc addition to N-(diphenylphosphinoyl) imines.     

SPINOL-derived phosphoric acids: synthesis and application in enantioselective Friedel-Crafts reaction of indoles with imines

A new class of chiral phosphoric acids with spirobiindane as scaffold were conveniently synthesized from (S)-1,1'-spirobiindane-7,7'-diol ((S)-SPINOL) and employed to catalyze the asymmetric Friedel-Crafts reaction of indoles with imines to afford 3-indolyl methanamines. High yields (68-97%) and excellent enantioselectivities (up to 99% ee) were obtained.     

The synthesis of chiral N-tosylatedaminoimine ligands and their application in enantioselective addition of phenylacetylene to imines

A class of new chiral tridentate N-tosylatedaminoimine ligands were synthesized and used in the Cu(I)-catalyzed enantioselective addition of phenylacetylene to imines. Good enantioselectivities in up to 91% ee were obtained.     

Quinoxaline-specific enantioselective sulfa-michael reaction catalyzed by chiral phosphoric acid

Highly enantioselective sulfa-Michael additions (SMA) between 2-alkenyl quinoxalines and aromatic thiols are accomplished using a low loading of chiral phosphoric acid catalyst (1 mol%). It was confirmed by an investigation of a lot of azaarenes that the two C=N units of quinoxalines are indispensable for controlling the reaction enantioselectivities. A series of non-terminal 2-alkenes substituted with aryls or alkyls, even other electro-withdrawing groups such as ketones, esters, or amides, selectively reacted and afforded the desired SMA products (48 examples) in good regioselectivities with high yields (up to 99%) and good ee values (up to 97%).     

Catalytic asymmetric addition of alcohols to imines: enantioselective preparation of chiral N,O-aminals

The enantioselective addition of alcohols to imine electrophiles has been shown to proceed in the presence of a catalytic amount of a chiral phosphoric acid catalyst. The reaction allows for the formation of the respective chiral N,O-aminals in excellent yield and enantioselectivity. A total of 11 different alcohols and 11 different imines were successfully used as a clear demonstration of the reaction generality.     

A chiral pyrrolidine-pyrazole catalyst for the enantioselective Michael addition of carbonyls to nitroolefins

An enantioselective Michael reaction of carbonyl compounds to nitroolefins has been accomplished using a novel chiral pyrrolidine-pyrazole catalyst. This newly prepared catalyst was found to be very effective in providing good yields as well as good diastereo- and enantio-selectivities. The mechanism of the reaction has also been substantiated by mass spectral studies.     

Discovery of chiral catalysts by asymmetric activation for highly enantioselective diethylzinc addition to imines: using racemic and achiral diimines as effective activators

A library of chiral zinc complexes formed in situ by the combination of achiral and racemic diimines with 3,3′-di(3,5-ditrifluoromethylphenyl)-BINOL and diethylzinc were evaluated in the asymmetric addition of diethylzinc to N-acylimines. In the presence of 10 mol % of chiral ligand 4 and racemic diimine 5, high enantioselectivities of up to 97% ee and yields of up to 96% were achieved for a wide range of aromatic imines in dichloromethane at −30 °C.     

Highly enantioselective direct conjugate addition of ketones to nitroalkenes promoted by a chiral primary amine-thiourea catalyst

Primary amine-thiourea derivative 1 is an active and highly enantioselective catalyst for the conjugate addition of ketones to nitroalkenes. Broad substrate scope is described, with nitroalkenes bearing either aromatic or aliphatic substituents and a wide variety of ketones shown to be useful reacting partners. Ethyl ketones react preferentially, generating anti products with methyl-bearing stereocenters with good-to-excellent diastereoselectivity. An enamine mechanism is indicated, with cooperative activation of the electrophile by the thiourea and of the ketone by the primary amine.     

Binaphthol-derived phosphoric acid as a versatile catalyst for enantioselective carbon-carbon bond forming reactions

Binaphthol-derived monophosphoric acids have been designed as novel chiral Br?nsted-acid catalysts. The chiral phosphoric acids thus developed function as efficient enantioselective catalysts for a variety of organic transformations, especially for carbon-carbon bond forming reactions.     

Simple chiral sulfonamide primary amine catalysed highly enantioselective Michael addition of malonates to enones

A chiral sulfonamide primary amine-organocatalysed, highly enantioselective Michael addition of malonates to enones has been developed. This reaction afforded the corresponding products in excellent yields (up to 99%) and excellent enantioselectivity (up to 99% ee).     

A new cationic,chiral catalyst for highly enantioselective Diels-Alder reactions

[reaction: see text] The Diels-Alder reaction of cyclopentadiene and 2-methacrolein is catalyzed by a chiral Lewis acid to form the exo adduct in 96% yield and 96% ee.     

l-Piperazine-2-carboxylic acid derived N-formamide as a highly enantioselective Lewis basic catalyst for hydrosilylation of N-aryl imines with an unprecedented substrate profile

[reaction: see text] l-Piperazine-2-carboxylic acid derived N-formamides have been developed as highly enantioselective Lewis basic catalysts for the hydrosilylation of N-aryl imines with trichlorosilane. The arene sulfonyl group on N4 was found to be critical for the high enantioselectivity of the catalyst. High isolated yields (up to 99%) and enantioselectivities (up to 97%) were obtained for a broad range of substrates, including aromatic and aliphatic ketimines, particularly those with R(2) as relatively bulky alkyl groups.     

Diphenylprolinol methyl ether: a highly enantioselective catalyst for Michael addition of aldehydes to simple enones

[reaction: see text] Diphenylprolinol methyl ether catalyzes intermolecular Michael addition of simple aldehydes to relatively nonactivated enones with the highest enantioselectivities reported to date (95-99% ee) and significantly lower catalyst loadings than have been typical in this arena.