Catalytic asymmetric diethylzinc addition to diphenylphosphionyl imines using chiral tert-butanesulfinylphosphine ligands

A class of novel chiral tert-butanesulfinylphosphine ligands were designed and synthesized by a concise two-step route with high yields. High activities and enantioselectivities (up to 94% ee) were achieved when using them in catalytic asymmetric diethylzinc addition to diphenylphosphionyl imines.     

New bis-steroidal axially chiral diols as ligands for the asymmetric addition of diethylzinc to aldehydes

New axially chiral steroidal binaphthols, prepared from estrone, were applied in the form of their Ti-alkoxides as catalysts for the addition of diethylzinc to aldehydes. The addition reactions proceeded with high yields and enantioselectivities up to 86%.     

Novel polymer-supported chiral catalysts for the asymmetric addition of diethylzinc to aldehydes

Newly synthesized polymer-supported chiral amino alcohol catalysts 5a and 5b have been proved to be effective for the enantioselective addition of diethylzinc to aldehydes, affording the corresponding sec-alcohols in moderate enantiomeric excesses with good to excellent yields. The recycled catalyst could be reused in the same reaction without significant deterioration in performance.     

Novel C2-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands: synthesis and application in asymmetric diethylzinc addition to aldehydes

First synthesis of C₂-symmetric chiral O,N,N,O-tetradentate 2,2-bipyridyldiolpropane ligands is described. The Mukaiyama–Michael reaction was applied as an important reaction for the synthesis of 2,2-bipyridylpropane 9. Among the ligands synthesized, ligand 11 exhibits excellent chiral induction (up to 97% ee) in diethylzinc addition to various aldehydes. The use of additional Lewis acid such as Ti(OⁱPr)₄ in diethylzinc addition reaction is not required for the present catalytic system.     

Iridium and rhodium complexes with the planar chiral thioether ligands in asymmetric hydrogenation of ketones and imines

Rhodium complexes with the planar chiral phosphinoferrocenyl thioether ligands [Rh(P,SR)(diene)X] (R = Me, Bu^t, Ph, Bn, diene is cyclooctadiene (COD) or norbornadiene (NBD), X = Cl, BF₄) catalyze hydrogenation of ketones, imines, and heteroaromatic compounds; in the case of acetophenone, the enantioselectivity reached 60% ee. Similar iridium complexes demonstrate a good activity in the hydrogenation of imines, the maximal enantioselectivity in the case of N-phenyl-N-(1-phenylethylidene)amine was about 40% ee.     

Aminosubstituted tert-butylsulfinylferrocenes as a new family of chiral ligands: asymmetric addition of diethylzinc to aldehydes

A ready access to a new family of planar chiral ferrocenes, the (RFc,RS)-2-amino substituted 1-tert-butylsulfinylferrocenes, is described; in the case of the sulfonamide series enantioselectivities of up to 96% were obtained in the addition of Et2Zn to aromatic aldehydes.     

Efficient asymmetric addition of diethylzinc to aldehydes using 3‐hydroxyazetidine derivatives as chiral ligands

A new series of chiral 3‐hydroxyazetidines has been prepared from (S)‐1‐(4‐methoxyphenyl)ethylamine. These ligands have shown excellent catalytic activities and enantiomeric selectivities in asymmetric addition of diethylzinc to aromatic aldehydes. Copyright © 2008 John Wiley & Sons, Ltd.     

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.     

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.     

Axially chiral tridentate isoquinoline derived ligands for diethylzinc addition to aldehydes

The synthesis and resolution of new tridentate isoquinoline-derived ligands has been developed. The key steps in the synthetic sequence include successive, chemo-selective Suzuki-Miyaura cross-couplings of 1,3-dichloroisoquinoline with suitable arylboronic acids. The new ligands prepared in this manner were resolved either via molecular complexation with N-benzylcinchonidinium chloride as with 1-[3-(2-hydroxyphenyl)isoquinolin-1-yl]naphthalen-2-ol or via chromatographic separation of its epimeric camphorsulfonates as for 1,3-bis-(2-hydroxynaphthalen-1-yl)isoquinoline. 4-tert-Butyl-2-chloro-6-[1-(2-hydroxymethylnaphthalen-1-yl)isoquinolin-3-yl]phenol was resolved by chiral semi-preparative HPLC. The application of these ligands in the diethylzinc addition to aldehydes was investigated. In certain cases, the desired secondary alcohols were obtained in high yield with excellent enantiomeric excess (ee?>?99%) at low catalyst loading (1?mol%).     

Novel and efficient chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

Easily prepared, chiral sulfideoxathiane ligands are described which give excellent enantioselectivity (up to 99% ee) in the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a range of alkyl malonate nucleophiles.     

A new pyrrolidine-derived atropisomeric amino alcohol as a highly efficient chiral ligand for the asymmetric addition of diethylzinc to aldehydes

A highly efficient pyrrolidine-derived atropisomeric amino alcohol, (S_a)-1-[2-diphenylhydroxymethyl-6-(trifluoromethyl)phenyl]-2-(1-pyrrolido)methyl-1H-pyrrole, has been synthesized as a chiral ligand for the enantioselective addition of diethylzinc to some prochiral aldehydes to afford (S)-alcohols. The conversion rates were close to quantitative with good to excellent enantiomeric excesses (up to 95% ee).     

Synthesis and application of oxadiazines as chiral ligands for the enantioselective addition of diethylzinc to aldehydes

A series of oxadiazines derived from l-phenylalanine bearing phenolic substituents have been synthesized in a multistep, one pot process. This process involves the reaction of a mixed anhydride with a β-hydrazino alcohol, methanesulfonylation of the alcohol moiety, and base induced cyclization. The resultant oxadiazines were employed in the asymmetric addition of diethylzinc to aldehydes.     

3-Aminoquinazolinones as chiral ligands in catalytic enantioselective diethylzinc and phenylacetylene addition to aldehydes

A series of readily known enantiomerically pure 3-aminoquinazolinones 1a–d were synthesised from easily accessible chiral pool α-hydroxy acids and α-amino acids in only four steps without any requirement of chromatography. These quinazolinones were examined as chiral ligands for catalytic enantioselective diethylzinc and phenylacetylene additions to aldehydes. For enantioselective alkylations, the effects of temperature, solvent, diethylzinc and ligand criteria were analysed, and the desired chiral alcohols were obtained in up to 86% ee. 3-Aminoquinazolinones 1a–d were also shown to be very useful ligands in enantioselective alkynylations of aldehydes. Based upon the optimised conditions, the corresponding propargylic alcohols were obtained in up to 94% ee.     

Novel chiral ammonium ionic liquids as efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins

Two chiral ammonium ionic liquids 1a and 1b have been newly synthesized from commercially available (+)-cis-2-benzamidocyclohexanecarboxylic acid. These CILs have been demonstrated to be efficient organocatalysts for asymmetric Michael addition of aldehydes to nitroolefins with excellent yields (up to 99%), high enantioselectivities (up to 90%) and modest to high diastereoselectivities (syn/anti ratio up to 99/1).     

Enantioselective addition of diethylzinc to N-diphenylphosphinoylimines employing cinchonidine and cinchonine as chiral ligands

The use of the `pseudoenantiomeric pair' of cinchonine and cinchonidine as ligands for the addition of diethylzinc to N-diphenylphosphinoylimines has been investigated. With 1 equiv of cinchonidine as ligand, a series of chiral amines was prepared in good yield and enantiomeric excesses of up to 94%. The use of 2.0 equiv of methanol as an achiral additive was found significantly to improve the selectivity of the addition when using 0.2 equiv of ligand, yielding ee's close to those obtained with a stoichiometric amount of ligand.     

Dramatic catalyst evolution in the asymmetric addition of diethylzinc to benzaldehyde

We have observed product ee's that begin at 20% at low reaction conversion and rise to 79% ee at the completion of the reaction in the asymmetric addition of alkyl groups to benzaldehyde. This rare behavior is attributed to autoinduction, in which the catalyst evolves by incorporation of the product. Based on this, we have been able to optimize the catalyst by variation of achiral, rather than enantiopure ligands.     

A chiral phosphepine–olefin rhodium complex as an efficient catalyst for the asymmetric conjugate addition

A monophosphine–olefin was synthesised from a 2,2′-bridged 1,1′-binaphthyl precursor, which served as a chiral bidentate ligand in the Rh catalysed 1,4-additions of arylboronic acids to cycloalkenones and 5,6-dihydro-2H-pyran-2-one. Fair yields (64–88%) and high asymmetric inductions (88–98% ee) have been obtained. The crystal structure of a corresponding cationic Rh(I) complex was determined.     

Highly enantioselective copper-catalyzed conjugate addition of diethylzinc to enones using chiral spiro phosphoramidites as ligands

Novel monodentate chiral spiro phosphoramidite ligands have been readily synthesized in good yields from enantiomerically pure 1,1'-spirobiindane-7,7'-diol. The new ligands were highly efficient in the copper-catalyzed conjugate addition of Et(2)Zn to enones with up to 98% enantiomeric excess.