Nonlinear effects in the enantioselective 1,4-conjugate addition of diethylzinc to chalcone

A clear positive nonlinear effect of the enantiopurity of ligand 1 on the product ee was observed in the enantioselective 1,4-conjugate addition of Et₂Zn to chalcone. The experimental data of nonlinear effect meet Kagan's ML₂ model.     

Photooxidation of arylmethyl bromides with mesoporous silica FSM-16

A mesoporous silica FSM-16 was found to be a recyclable oxidizing promoter of arylmethyl bromides for the preparation the corresponding carboxylic acids, aldehydes, or ketones under photoirradiation conditions.     

Inositols as chiral templates: 1,4-conjugate addition to tethered cinnamic esters

The 1,4-addition of thio nucleophiles to chiro-inositols containing a cinnamyl Michael acceptor proceeded with excellent diastereochemical induction and good yields. Cleavage of the inositol auxiliary provides beta-thio hydrocinnamic acids in >99% ee's.     

Advances on asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media

Asymmetric Michael addition reactions or 1,4-conjugate addition reactions are considered to be the fundamental C–C bond-forming reaction for the construction of chiral β-nitro, β-carbonyl and several other important structural motifs in organic synthesis. After the development of many chiral metal complexes as catalysts, a tremendous growth in the design and applications of variety of new chiral organocatalysts for asymmetric 1,4-conjugate addition reactions has been witnessed over the last two decades. Initially, asymmetric organocatalysis has been performed in organic solvents, but gradually performing the same catalysis in aqueous and semi-aqueous media became a necessity due to environmental aspects as well as to achieve better reactivity and selectivity. The structural and functional diversity of the chiral organocatalysts derived from natural and synthetic sources utilized differently the water either as the sole solvent, co-solvent or additive for optimising their best performances. In the present review, we discuss a detailed and comprehensive report on the advancement in the field of asymmetric organocatalytic 1,4-conjugate addition reactions in aqueous and semi-aqueous media.     

The ortho effect: copper-catalyzed highly enantioselective 1,4-conjugate addition of diethylzinc to chalcones

The copper-catalyzed enantioselective 1,4-conjugate addition of diethylzinc to chalcones was investigated in the presence of a catalytic amount of N,P-ferrocenyl ligands with central and planar chirality under mild conditions (0 °C→rt). It was found that chalcones with ortho-substituents (from ortho-substituted benzaldehydes and acetophenone/substituted acetophenones) led to a dramatic improvement in the enantioselectivities. The (R)- and (S)-antipodes of the addition reaction were obtained with up to 92% ee after this transformation.     

Rhodium catalyzed 1,4-conjugate addition of 1,5-azastibocines with electron deficient olefins

The rhodium-catalyzed reaction of Sb-aryl-1,5-azastibocines with alpha,beta-unsaturated ketones and esters is described. Exclusive formation of 1,4-conjugate adduct was achieved in aqueous NMP (N-methyl-2-pyrrolidinone) in the presence of 5 mol% of [RhCl(cod)](2), and no formation of Heck adduct was observed in this condition. Reactions with various enones and enoates were also demonstrated to prove generality of the 1,4-conjugate addition.     

Catalytic enantioselective addition of diethylzinc to (hetero)aromatic aldehydes

The asymmetric alkylation with diethylzinc of five heterocyclic aldehydes and benzaldehyde (for comparison) has been studied in the presence of two optically active amino alcohols: (S)-2-amino-1-butanol (AB) and (1S,2R)-N,N-dibutylnorephedrine (DBNE). A number of chiral (hetero)aromatic secondary alcohols were synthesized in high yields (95–98%) with enantioselectivity up to 92% enantiomeric excess (ee) in the presence of DBNE catalyst. Optically active thienyl and 4-pyridyl derivatives were prepared for the first time by catalytic asymmetric alkylation. The influence of the amount of DBNE on the enantioselectivity was investigated. In contrast to benzaldehyde, 2-furan- and 2-thiophene-carbaldehydes, in the case of 3- and 4-pyridinecarbaldehydes the ee values depend directly on the catalyst concentration. © 1998 John Wiley & Sons, Ltd.     

(R)-4-menthenone in reactions of 1,4-conjugate and 1,3-dipolar addition

(R)-4-Menthenone compared with common cyclic enones exhibits considerably lower reactivity in 1,4-conjugate addition of organometallic reagents, is inert in Michael reactions and pyrazoline formation evidently due both to the distorted polarization in the enone system and to steric hindrances from the α-isopropyl group in the cyclohexene ring.     

The first examples of rhodium-catalyzed 1,4-conjugate addition reactions of arylboronic acids with ethenesulfonamides

An unprecedented rhodium-catalyzed 1,4-conjugate addition of arylboronic acids with ethenesulfonamides resulting in the corresponding 2-arylethanesulfonamides is described. The amino substituent, the applied arylboronic acid, the type of Rh-catalyst, and the experimental conditions all affected the reaction outcome.     

Ruthenium(ii)-catalyzed regioselective 1,6-conjugate addition of umpolung aldehydes as carbanion equivalents

One of the most efficient and reliable approaches to construct C–C bonds involves the conjugate addition of carbon nucleophiles to electron-deficient ketones. Yet, 1,6-conjugate additions of extended conjugated systems largely remain underexplored due to difficulties in controlling the regioselectivity. Herein, we report umpolung aldehydes as carbanion equivalents for highly regioselective 1,6-conjugate addition reactions to unsaturated ketones, with preliminary studies of the enantioselective variant. The synergy of ruthenium(ii) catalyst and electron-rich, bidentate phosphine ligand is essential for the reactivity and selectivity under mild reaction conditions.

Highly regioselective 1,6-conjugate addition was developed using hydrazone as carbanion equivalent catalyzed by ruthenium under mild conditions.     

Isoleucine-catalyzed direct asymmetric aldol addition of enolizable aldehydes

Isoleucine-catalyzed direct enantioselective aldol additions between enolizable aldehydes are reported. Intermediate acetal structures dictate the configurative outcome and were supported by a hydrogen bond. This direct isoleucine-catalyzed aldol addition represents a welcome complement to both proline- and histidine-catalyzed aldol additions of enolizable aldehydes.     

Highly enantioselective 1,4-conjugate addition of dialkylzinc to α,β-unsaturated lactone catalyzed by diphosphite-copper complexes

The 1,4-addition of diethylzinc and dimethylzinc to 5,6-hydro-2H-pyran-2-one using new chiral diphosphite-copper catalysts gave products in up to 98% ee.     

新型P,N配体及基1,4-共轭加成反应

以2-萘酚为起始原料,经过氧化偶联,消旋体的拆分得到手性骨架2-氨基-2'-羟基-1,1'-联萘(NOBIN),并以S-NOBIN为原料,经过六步反应合成了两个新型配体S-(+)-2-(2-吡啶酰胺基)-2'-二苯基膦基-1,1'-联萘(1a)和S-(+)-2-(6-甲基-2-吡啶酰胺基)-2'-二苯基膦基-1,1'-联萘(1b)。并进行了铜配合物催化的二乙基锌对2-环己烯酮的1,4-共轭加成反应的研究。反应产物3-乙基环己酮(13)的e.e.值高达92%。     

Enantioselective addition of diethylzinc to aldehydes catalyzed by optically active 1,4-aminoalcohols

Enantioselective addition reactions of diethylzinc to aldehydes were performed by catalytic reactions with chiral 1,4-aminoalcohols. Optically active 1,4-aminoalcohols were synthesized from (+)-camphor and (−)-fenchone through four steps involving iodine-mediated lactonization of 3-hydroxy acids.     

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.     

An enantioselective catalytic approach to syn deoxypropionate units combining asymmetric Cu-catalyzed 1,6- and 1,4-conjugate addition

A novel iterative approach to the synthesis of the naturally ubiquitous syn deoxypropionate motif is reported. The route comprises a new Horner–Wadsworth–Emmons reagent to prepare α,β,γ,δ-bisunsaturated thioesters. Next, two Me-substituents are introduced in high yield, regio- and enantioselectivity using sequential asymmetric Cu-catalyzed 1,6-conjugate addition, base-catalyzed olefin isomerization and Cu-catalyzed enantioselective 1,4-conjugate addition. After reduction to the aldehyde these transformations can be repeated to install three or more Me groups with a syn 1,3-relationship.