Copper-catalyzed enantioselective conjugate addition of diethylzinc using axially chiral aminoethyloxy-phosphine ligands

New axially chiral P,O,N-type ligands bearing both a diphenylphosphino group and 2-(dialkylamino)ethyloxy (or 2-pyridylmethyloxy) groups were designed and prepared along with P,O,O-type ligands by employing an easily available chiral component, (R)-2-hydroxy-2′-diphenylphosphinyl-1,1′-binaphthyl. Among the ligands the simplest P,O,N-type one bearing a 2-(dimethylamino)ethyloxy group was found to be the most efficient in copper-catalyzed enantioselective conjugate addition of diethylzinc to a cyclic enone, 2-cyclohexen-1-one, providing high enantioselectivity up to 99% ee.     

Copper-catalyzed asymmetric conjugate addition of trialkylaluminium reagents to trisubstituted enones: construction of chiral quaternary centers

Me3Al, Et3Al, and vinylalane species undergo enantioselective conjugate addition to a wide range of 2- or 3-substituted enones (cyclopent-2-enones, cyclohex-2-enones, 3-methyl cyclohept-2-enone) in the presence of catalytic amount of copper salt (copper thiophene carboxylate, [Cu(CH3CN)4]BF4 or [CuOTf]2C6H6) and tropos-phosphoramidite-based ligand. Thus, chiral quaternary centers can be built, with up to 98% ee after rigorous optimization of experimental conditions. It was shown that the main important parameter was the order of the introduction of the reagents. Then, the generated enantioenriched aluminium enolates and the chiral conjugate adducts were functionalized and used for subsequent reactions.     

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.     

Copper-catalyzed asymmetric conjugate addition of diethylzinc to alpha,beta-unsaturated imines derived from alpha-aminoacids. Enantioselective synthesis of gamma-substituted alpha-dehydroaminoesters

[Structure: see text] A highly enantioselective synthesis of alpha-dehydroaminoacids with a stereogenic center in the gamma position through copper-catalyzed asymmetric conjugate addition of diethylzinc to alpha,beta-unsaturated imines using a TADDOL-derived phosphoramidite complex is reported.     

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted enones. Construction of all-carbon quaternary chiral centers

The copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted cyclic enones affords enantioenriched all-carbon quaternary centers with up to 96% ee. The chiral ligand is a diaminocarbene, directly generated in situ. The combination of Grignard reagent and diaminocarbene is unprecedented in conjugate addition, and the additon of the phenyl group, on such enones, cannot be done by other conjugate addition methods.     

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.     

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.     

Application of ferrocenyl substituted aziridinylmethanols (FAM) as chiral ligands in enantioselective conjugate addition of diethylzinc to enones

Easily available ferrocenyl substituted aziridinylmethanol FAM-4a complexes with nickel and catalyzes the enantioselective diethylzinc addition to various enones with enantiomeric excesses reaching 80%. The ligand can be recovered and used without losing its activity. The sense of induction was found to be dependent on the configuration of the aziridine ring.     

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).     

Copper-catalyzed asymmetric conjugate addition with Grignard reagents and SimplePhos ligands

Herein we report the copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic and acyclic enones, with SimplePhos as chiral ligands. A variety of Grignard reagents can be added to a range of cyclic and acyclic enones, with moderate to good enantioselectivities (ee’s up to 86%).     

Copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones in the presence of planar-chiral phosphaferrocene-oxazoline ligands

[reaction: see text] A new subclass of chiral phosphaferrocene-oxazoline ligands has been applied to the copper-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones, furnishing good enantioselectivity. The ligand design readily lends itself to modification, thereby facilitating optimization of ee. Although the dominant stereocontrol element in these 1,4-addition processes is the central chirality of the oxazoline subunit of the ligand, not the planar chirality of the phosphaferrocene, altering the phosphaferrocene subunit can provide useful enhancement of enantioselectivity.     

The first catalytic asymmetric addition of diethylzinc to aldehyde promoted by chiral thiourea

A series of C₂-symmetric and asymmetric chiral thiourea derivatives were synthesized from commercial L-phenylalanine.All of the new compounds have been fully characterized by IR,¹H NMR,¹³C NMR,MS spectra and elemental analyses.The chiral thioureas were used as chiral ligands in the catalytic enantioselective ethylation of aldehydes with diethylzinc,the corresponding sec-alcohols were gained with excellent enantioselectivities（up to 87.1%ee） and high yields（up to 76.7%） after the conditions were optimized.     

N-Allyl-N-tert-butyldimethylsilylamine for chiral ligand-controlled asymmetric conjugate addition to tert-butyl alkenoates

The chiral ligand controlled asymmetric conjugate addition reaction of lithium N-allyl-N-(tert-butyldimethylsilyl)amide to alkenoates proceeded smoothly to give, after protodesilylation, the corresponding 3-allylaminoalkanoates with high enantioselectivities in high yields. The allyl group on the nitrogen atom was easily removable to afford 3-aminoalkanoates.     

Copper-catalyzed enantioselective conjugate addition of dialkylzinc reagents to (2-pyridyl)sulfonyl imines of chalcones

[reaction: see text] The enantioselective catalytic 1,4-addition to alpha,beta-unsaturated ketimines is an unprecedented process. Herein, we document the copper-catalyzed addition of dialkylzinc reagents to (2-pyridylsulfonyl)imines of chalcones. This process occurs rapidly in the presence of a chiral phosphoramidite ligand to afford exclusively the 1,4-addition product. In the case of addition of dimethylzinc, enantioselectivities in the range 70-80% ee are obtained. The presence of the metal-coordinating 2-pyridylsulfonyl group proved to be essential for this reaction to proceed.     

Formation of highly substituted chiral cyclohexanone derivatives using a tandem conjugate addition/cyclisation

A tandem conjugate addition/cyclisation approach, that allows the synthesis of chiral highly substituted cyclohexanones and cyclohexenones, which is applicable to natural product syntheses has been developed.     

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.     

Stereocontrolled enantioselective addition of diethylzinc to aldehydes using new chiral aminoalcohols

The new chiral β-aminoalcohols of indolinylmethanols ( 1 ) and their reduced derivatives ( 2 ) were synthesized from (S)-indoline-2-carboxylic acid. Both (R) and (S) enantiomers of the optically active secondary alcohols have been successfully obtained in high enantiomeric excess from the stereoselective addition of diethylzinc to the aldehydes catalyzed by the chiral aminoalcohols ( 1 and 2 ). The sense of the asymmetric induction and the degrees of enantioselectivities turned out to be highly dependent on the structure of the catalysts: The presence of the catalyst 1 afforded the (S)-configuration of the corresponding alcohols; on the other hand, the presence of 2 afforded the (R)-configuration of the alcohols in high enantiomeric selectivity.     

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.     

P-chiral o-phosphinophenol as a P/O hybrid ligand: preparation and use in Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones

[reaction: see text] (S)-2-(tert-Butylmethylphosphino)phenol and its methyl ether were synthesized from tert-butyldichlorophosphine via optically active phosphine-boranes as the intermediates. The former compound was used as a P/O hybrid ligand in the Cu-catalyzed asymmetric conjugate addition of diethylzinc to acyclic enones to achieve high enantioselectivity of up to 96%.     

New chiral Schiff base as a tridentate ligand for catalytic enantioselective addition of diethylzinc to aldehydes

We have developed new chiral Schiff base catalysts for the enantioselective addition of diethylzinc reagents to aldehydes. The reaction of benzaldehyde with diethylzinc in the presence of 1 mol % of the chiral Schiff base catalyst proceeded to afford 1-phenyl-1-propanol in 96% enantiomeric excess (ee).