Iridium-catalyzed asymmetric ring opening of azabicyclic alkenes by amines

The enantioselective ring-opening reactions of azabicyclic alkenes with primary and secondary aromatic amine nucleophiles are reported using an iridium catalyst generated in situ from 1.5 mol % of [Ir(COD)Cl](2) and 3 mol % of (S)-BINAP. The reaction affords the corresponding trans-1,2-diamine derivatives in moderate to good yields with moderate to high enantioselectivities (up to 97% ee). The trans-configuration of the 1,2-diamino product 2g was confirmed by X-ray crystallography.     

Highly effective and enantioselective Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones promoted by simple chiral primary amine thiourea bifunctional catalysts

Highly asymmetric Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketones promoted by chiral primary amine thiourea bifunctional catalysts was developed and a series of Michael adducts were obtained in excellent yields (up to 97%) and enantioselectivities (up to 95% ee). Optically pure S-warfarin was easily obtained in 99% ee after single recrystallization.     

Copper-catalyzed asymmetric propargylic amination of propargylic acetates with amines using BICMAP

The copper-catalyzed asymmetric propargylic amination of propargylic acetates 1 with amines 2 using BICMAP as a chiral ligand gave the desired products 3 in good yields and with moderate to high enantioselectivities (up to 90% ee).     

Direct catalytic enantioselective alpha-aminomethylation of aldehydes

The direct catalytic asymmetric alpha-aminomethylation of aldehydes is presented. The chiral amine and amino acid catalyzed reactions between unmodified aldehydes and a formaldehyde-derived imine precursor were fast and proceeded with high chemo- and enantioselectivities. The corresponding dibenzyl-protected gamma-amino alcohols were isolated in high yields with up to 98% ee after in situ reduction. The reaction is a novel entry to valuable beta(2)-amino acid derivatives.     

Synthesis of novel nitrogen-containing polymers by Pd(0)-catalyzed polycondensation of propargylic carbonates and bifunctional nitrogen nucleophiles

A Pd(0)-catalyzed polycondensation of propargylic carbonates and bifunctional nitrogen nucleophiles was investigated. The polycondensation was carried out in THF at 80 °C for 20 h in the presence of a Pd(0) catalyst. The Pd(0)-catalyzed polycondensation with bifunctional nitrogen nucleophiles proceeded successfully when bis[(2-diphenylphosphino)phenyl]ether (DPEphos) was used as the ligand. N-monoalkylated bifunctional benzenesulfonamides and pyromellitic diimide could be used in the polycondensation. Aliphatic and aromatic amines did not afford the corresponding polymers at all. The molecular weights of the obtained polymers were higher when propargylic carbonates having an aryl group on the acetylenic terminal carbon were used.     

Enantioselective 1,6-Michael addition of anthrone to 3-methyl-4-nitro-5-alkenyl-isoxazoles catalyzed by bifunctional thiourea-tertiary amines

A simple and efficient method for the enantioselective 1,6-Michael addition reaction of anthrone to a series of 3-methyl-4-nitro-5-alkenyl-isoxazoles with a bifunctional thiourea-tertiary amine as catalyst is described. This transformation proceeds smoothly with 10 mol % catalyst and provides a series of Michael adducts bearing 3-methyl-4-nitro-isoxazole and anthrone units with good to high enantioselectivities (up to 96% ee) and in very high yields (up to 99%).     

手性氨基醇催化的苯乙炔与酮的对映选择性加成

(S)-(1-Benzylpyrrolidin-2-yl)diphenylmethanol and cinchonine were evaluated as promotors in the asymmetricadditions of phenylacetylene to ketones,in order to prepare chiral propargylic alcohols.Good yields(up to 89%)and moderate enantioselectivities(up to 77.9% ee)were achieved.Addition of Ti(OPr-i)_4 can significantly improvethe enantioselectivity of the reaction.     

Brønsted acid-catalyzed imine amidation

A new method for the Br?nsted acid-catalyzed addition of amide nucleophiles to imines to produce protected aminal products is described. Simple Br?nsted acids (phenyl phosphinic acid and trifluoromethanesulfonimide) were shown to be excellent catalysts, providing high yields of the aminal product. A catalytic asymmetric imine amidation using sulfonamides as nucleophiles was successful when a hindered biaryl phosphoric acid catalyst derived from 2,2'-diphenyl-[3,3'-biphenanthrene]-4,4'-diol (VAPOL) was used. Excellent yields and enantioselectivities were found in these additions (up to 99% ee).     

Enantioselective conjugate addition of both aromatic ketones and acetone to nitroolefins catalyzed by chiral primary amines bearing multiple hydrogen-bonding donors

A new class of chiral primary amine catalysts bearing multiple hydrogen-bonding donors have been designed and synthesized. The newly developed bifunctional organocatalysts efficiently catalyzed not only enantioselective conjugate addition of aromatic ketones to nitroolefins in good yields (up to 87%) with excellent enantioselectivities (97→99% ee) but also enantioselective conjugate addition of acetone to nitroolefins in excellent yields (90-96%) with high enantioselectivities (up to 97% ee).     

Primary amine catalyzed aldol reaction of isatins and acetaldehyde

Several cinchona alkaloid-derived chiral primary amines were applied as the catalyst for the cross aldol reaction of isatins with acetaldehyde. With the quinine-derived amine catalyst 3, the desired aldol products were obtained in high yields and good enantioselectivities (up to 93% ee) under the optimized conditions. Although other enolizable aldehydes and ketones may also be applied in this reaction, the ee values obtained are usually low. A mechanism was proposed to account for the formation of the major enantiomer in this reaction.     

Enantioselective alkynylation of carbonyl compounds with trimethoxysilylalkynes catalyzed by lithium binaphtholate

Enantioselective alkynylation of aldehydes and ketones was accomplished using trimethoxysilylalkynes as alkynylating reagents and lithium 3,3′-diphenylbinaphtholate as a catalyst. Optically active propargylic alcohols were obtained in good to high chemical yields and enantioselectivities. Alkynylation of acetylpyridines afforded biologically active pyridyl propargylic alcohols in good enantioselectivities.     

Chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

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

Catalytic and highly enantioselective reactions of alpha-sulfonyl carbanions with chiral bis(oxazoline)s

The enantioselective reactions of lithiated benzyl trifluoromethyl sulfones with a substoichiometric amount of a bis(oxazoline) and various aldehydes is disclosed. The products were formed with excellent diastereo- and enantioselectivities. Fluorination of the sulfone with N-fluorobenzenesulfonimide and a stoichiometric amount of a bis(oxazoline) gave products with extremely high enantioselectivities (up to 99% ee; ee=enantiomeric excess). The enantioselective reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.     

Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and aldehydes

Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent enantioselectivities with up to 98% ee and 94% ee, respectively.     

Enamines: efficient nucleophiles for the palladium-catalyzed asymmetric allylic alkylation

Enamines were tested to be efficient nucleophiles for palladium-catalyzed asymmetric allylic alkylation, avoiding the use of unstablilized ketone enolates formed by strong bases. The influence of the chiral metallocene-based ligands upon this reaction was studied in detail. It was shown that planar chirality played an important role in enantioselectivities. Meanwhile, different kinds of enamines and allylic acetate to the reactions were also investigated. High catalytic activity and excellent enantioselectivity (up to 99% ee) were obtained with pyrrolidine enamines of both aliphatic and aromatic ketone.     

Phosphoramidite ligands in iridium-catalyzed allylic substitution

A new phosphoramidite ligand was used in the iridium-catalyzed allylic substitution reaction. This permitted high regio- and enantioselectivities on a wide variety of substrates and nucleophiles. Because of the stereospecificity of the reaction obtained by using branched substrates, a kinetic resolution reaction was attempted. The origin of the impressive efficiency of this ligand in terms of kinetics was explored in detail, as was the role of the substituent in the ortho-position of the amine moiety.     

Chiral amine thiourea-promoted enantioselective Michael addition reactions of 3-substituted benzofuran-2(3H)-ones to maleimides

A highly diastereo- and enantioselective Michael addition reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and maleimides by a chiral bifunctional thiourea-tertiary amine catalyst was investigated. The corresponding adducts, containing a quaternary center at the C3-position of the benzofuran-2(3H)-one as well as a vicinal tertiary center, were generally obtained in high yields (up to 99%) with very good diastereo- (up to >20:1 dr) and enantioselectivities (up to 97% ee).     

Asymmetric hydroxyamination of oxindoles catalyzed by chiral bifunctional tertiary amine thiourea: construction of 3-amino-2-oxindoles with quaternary stereocenters

Chiral bifunctional tertiary amine thiourea was applied to catalyze the asymmetric hydroxyamination of 3-subsituted oxindoles with nitrosobenzene to construct 3-amino-2-oxindoles with quaternary stereocenters in good yields (up to 91%) and enantioselectivities (up to 90% ee).     

Enantioselective zinc/BINOL-catalysed alkynylation of aldimines generated in situ from α-amido sulfones

Chiral nonracemic N-Cbz-protected propargylic amines have been prepared by the addition of terminal alkynes to imines generated in situ from α-amido sulfones in the presence of diethylzinc and BINOL-type ligands as catalysts. The reactions give good yields and high enantioselectivities (ee values up to 95?%) for a good number of aromatic and heteroaromatic α-amido sulfones and alkynes.     

Asymmetric diethyl- and diphenylzinc additions to aldehydes by using a fluorine-containing chiral amino alcohol: a striking temperature effect on the enantioselectivity, a minimal amino alcohol loading, and an efficient recycling of the amino alcohol

A chiral pyrrolidinylmethanol derivative containing perfluoro-ponytails (5) was prepared from (S)-proline. The use of this perfluoro-substituted amino alcohol in catalytic asymmetric additions of organozinc reagents to aldehydes affords products with high enantioselectivities in both pure hexane and a mixture of hexane and FC-72 (perfluorohexane). Enantiomeric excesses up to 94 and 88 % ee have been achieved in Et(2)Zn and Ph(2)Zn additions, respectively. For the reactions in the biphasic solvent system a striking temperature effect was observed. Thus, when the temperature was raised from 0 to 40 degrees C the ee value of the product increased from 81 to 92 %. Furthermore, the catalyst loading could be remarkably low, and with only 0.1 mol % of amino alcohol 5 a product with 90 % ee was obtained in the Et(2)Zn addition to benzaldehyde in hexane. The perfluoro-ligand was easily recovered by simple phase separation, and until the ninth repetition its reuse proceeded without significant loss of enantioselectivity and reactivity.