Highly diastereo- and enantioselective one-pot Michael-Aldol reactions of α,β-unsaturated aldehydes with imidazole derivatives

Highly diastereo- and enantioselective one-pot Michael-Aldol reactions of α,β-unsaturated aldehydes with imidazole derivatives have been developed. The cascade reactions products could be obtained with three stereocenters in high yields and excellent diastereo- and enantioselectivities.     

A new class of metal-free catalysts for direct diastereo- and regioselective Mannich reactions in aqueous media

Camphor sulfonic acid is an efficient catalyst for Mannich reactions of benzaldehyde, aniline and various ketones in aqueous media, with diastereo- or regioselectivities. Meanwhile, three sulfonated amino acids can catalyze the same type of reactions effectively with high diastereo- or regioselectivities.     

NHC-catalyzed/titanium(IV)-mediated highly diastereo- and enantioselective dimerization of enals

An NHC-catalyzed, diastereo- and enantioselective dimerization of enals has been developed. The use of Ti(Oi-Pr)(4) is a key element for the reactivity and selectivity of this process. The cyclopentenes are obtained with high levels of diastereo- and enantioselectivity and their synthetic utility is demonstrated by functionalization of the product alkene.     

Highly diastereo- and enantioselective construction of phthalide-oxindole hybrids bearing vicinal quaternary chiral centers via an organocatalytic allylic alkylation

A diastereo- and enantioselective synthesis of phthalide-oxindole hybrids including congested adjacent quaternary chiral centers was demonstrated through a Lewis base catalyzed asymmetric allylic alkylation reaction of Morita–Baylis–Hillman carbonates of isatins and 3-cyanophthalides. The various hybrid molecules with two valuable pharmacophores-combined frameworks can be obtained in good to high diastereo- and enantioselectivities.     

Organocatalytic asymmetric epoxidation reactions in water-alcohol solutions

The diastereo- and enantioselective organocatalytic epoxidation of alpha,beta-unsaturated aldehydes in aqueous solutions is presented. By the screening of the reaction conditions for the epoxidation of cinnamic aldehyde applying hydrogen peroxide as the oxidant and 2-[bis-(3,5-bis-trifluoromethyl-phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine as the catalyst, a highly stereoselective reaction has been developed. The scope of the diastereo- and enantioselective organocatalytic epoxidation in aqueous solutions is documented by the asymmetric epoxidation of alpha,beta-unsaturated aldehydes with enantioselectivities up to 96% ee.     

Organocatalytic functionalization of carboxylic acids: isothiourea-catalyzed asymmetric intra- and intermolecular Michael addition--lactonizations

Tetramisole promotes the catalytic asymmetric intramolecular Michael addition-lactonization of a variety of enone acids, giving carbo- and heterocyclic products with high diastereo- and enantiocontrol (up to 99:1 dr, up to 99% ee) that are readily derivatized to afford functionalized indene and dihydrobenzofuran carboxylates. Chiral isothioureas also promote the catalytic asymmetric intermolecular Michael addition-lactonization of arylacetic acids and α-keto-β,γ-unsaturated esters, giving anti-dihydropyranones with high diastereo- and enantiocontrol (up to 98:2 dr, up to 99% ee).     

Asymmetric domino aza-Michael–Michael reaction of o-N-protected aminophenyl α,β-unsaturated ketones: construction of chiral functionalized tetrahydroquinolines

The diastereo- and enantioselective synthesis of 2,3,4-trisubstituted tetrahydroquinolines has been developed through organocatalytic domino aza-Michael–Michael reaction of o-N-tosylaminophenyl α,β-unsaturated ketones with nitroalkenes. This useful and simple domino process afforded diverse highly functionalized tetrahydroquinolines, some of which are not easily accessible using other methodologies, in good yields and with excellent diastereo- and enantioselectivities (up to >30:1 dr, >99% ee).     

Chiral biscinchona alkaloid promoted asymmetric allylic alkylation of 3-substituted benzofuran-2(3H)-ones with Morita-Baylis-Hillman carbonates

A highly diastereo- and enantioselective asymmetric allylic alkylation reaction with respect to prochiral 3-substituted benzofuran-2(3H)-ones and MBH carbonate by a chiral biscinchona alkaloid 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 97%) with very good diastereo- (up to 98:2 dr) and enantioselectivities (up to 95% ee).     

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).     

A new (S)-prolinamide modified by an ionic liquid moiety—a high performance recoverable catalyst for asymmetric aldol reactions in aqueous media

New prolinamide derivatives modified with ionic liquid moieties were synthesized and studied as organocatalysts in asymmetric aldol reactions in water. Aldol reactions between cycloalkanones or methylketones and aromatic aldehydes proceeded under studied conditions with high conversions (yields), diastereo- and enantioselectivities in the presence of a hydrophobic catalyst bearing a PF₆ anion (1-5 mol %). The procedure is scalable and the catalyst retained its diastereo- and enantioselectivity over at least four reaction cycles and its activity over at least three reaction cycles.     

A diastereo- and enantioselective synthesis of alpha-substituted anti-alpha,beta-diaminophosphonic acid derivatives

Highly diastereo- and enantioselective additions of alpha-nitrophosphonates to imines catalyzed by a chiral Br?nsted acid are described.     

Uncatalyzed asymmetric diels-alder addition of cyclopentadiene to (E)- and (Z) - (R) -4,5-di-O-isopropylidene-pent-2-enonates

The uncatalyzed Diels-Alder addition of cyclopentadiene to the acrylic ester derivatives {=1} proceeds with high diastereo- and enantioface selectitivity.     

Organocatalytic asymmetric synthesis of alpha,alpha-disubstituted alpha-amino acids and derivatives

It is shown that racemic oxazolones are excellent reagents for the synthesis of chiral quaternary amino acids and its derivatives by the diastereo- and enantioselective nucleophilic addition to alpha,beta-unsaturated aldehydes catalyzed by diarylprolinol silyl ethers. The scope of this new organocatalytic reaction is demonstrated for different oxazolones having aromatic and alkyl groups at the reactive carbon atom and different aromatic and aliphatic substituted alpha,beta-unsaturated aldehydes, for which the stereoselective reaction proceeds with good yield, moderate to good to very high diastereoselectivity, and very high enantioselectivity. The potential of the reaction is shown for the synthesis of optically active alpha,alpha-disubstituted alpha-amino acids, alpha-quaternary proline derivatives, amino alcohols, lactams, and tetrahydropyranes. Furthermore, we have calculated by DFT-methods the transition-state structures that account for both the diastereo- and enantioselectivity observed for the addition of oxazolones to the alpha,beta-unsaturated aldehydes. For one class of compounds, the stereoselectivity is controlled by a hydrogen-bonding interaction of the enolate-form of the oxazolone with an ortho-hydroxy-phenyl substituent of the alpha,beta-unsaturated aldehyde, whereas the benzhydryl-protecting group in the oxazolone determines the diastereo- and enantioselectivity in a more general manner for both aromatic and aliphatic alpha,beta-unsaturated aldehydes.     

Diastereo- and Enantioselective Hydrophosphination of Cyclopropenes under Lanthanocene Catalysis

The asymmetric hydrophosphination of cyclopropenes with phosphines is of much interest and importance, but has remained hardly explored to date probably because of the lack of suitable catalysts. We report here the diastereo- and enantioselective hydrophosphination of 3,3-disubstituted cyclopropenes with phosphines by a chiral lanthanocene catalyst bearing the C₂-symmetric 5,6-dioxy-4,7-trans-dialkyl-substituted tetrahydroindenyl ligands. This protocol offers a selective and efficient route for the synthesis of a new family of chiral phosphinocyclopropane derivatives, featuring 100 % atom efficiency, good diastereo- and enantioselectivity, broad substrate scope, and no need for a directing group.     

Asymmetric synthesis of cyclopropanes from lithiated aryloxiranes and alpha,beta-unsaturated Fischer carbene complexes

A diastereo- and enantiospecific formation of tetrasubstituted cyclopropane carbene complexes and cyclopropanecarboxylates from lithiated aryloxiranes and alpha,beta-unsaturated Fischer carbene complexes is described.     

Chiral pyrrolidinium salts as organocatalysts in the stereoselective 1,4-conjugate addition of N-methylpyrrole to cyclopent-1-ene carbaldehyde

A variety of enantiopure proline derived pyrrolidinium (HX)_n salts have been found to catalyse the 1,4-conjugate addition of N-methylpyrrole to cyclopent-1-ene carbaldehyde with, in some cases, high diastereo- and enantioselectivity. Parameters such as water activity, choice of acidic cocatalyst (HX)_n and also the amount of cocatalyst used turned out to be crucial for the diastereo- and enantioselectivity of the reaction.     

Direct organocatalytic asymmetric reductive Mannich-type reactions

A direct asymmetric reductive Manich-type reaction that allows for the formation of three contiguous stereocenters with high chemo-, diastereo-, and enantioselectivity is presented.     

Silicon-mediated enantioselective synthesis of structurally diverseα-amino acid derivatives

The catalytic asymmetric synthesis of novel and chiral amino acid derivatives with unconventional chemo-, diastereo-, and enantio-selectivity remains a paramount challenge. Herein we reported a novel protocol for the use of highly enantioselective copper-catalyzed cycloaddition of α,β-unsaturated acylsilanes as a springboard reaction for the facile synthesis of structurally diversified pyrrolidines and complicated α-amino esters by desilylation. The newly developed process could provide a wide range of synthetically useful acylsilane-substituted pyrrolidines(ASiP) in high yields and excellent diastereo-and enantioselectivities with Cu/(R)-XylBINAP complex as the catalyst. And the downstream desilylation transformation enables to expand the potntial applications of 1,3-dipolar cycloaddition in the construction of structurally unique amino acid derivatives, in which an unprecedented and concerted fluoride anion-promoted C–X(X=H, Si, N, C) bond cleavage occurred to the enantioselective construction of aldehyde-substituted pyrrolidines, linear cinnamaldehyde or alkene-substituted amino esters in high ee values.     

Camphor containing organocatalysts in asymmetric aldol reaction on water

A new class of bifunctional organocatalysts were synthesized and proved to be effective in catalyzing aldol reaction on water with high to excellent diastereo- and enantioselectivities.     

A diastereo- and enantioselective Michael addition of chiral amide enolates to α, β-unsaturated esters a stereoelective synthesis of (+)-dehydroiridodiol and (−)-isodehydroiridodiol

(+)-Dehydroiridodiol and (−)-isodehydroiridodiol were synthesized stereoselectively using the diastereo- and enantioselective Michael addition of chiral amide enolates to α, β-unsaturated esters.