Ru/Me-BIPAM-catalyzed asymmetric addition of arylboronic acids to aliphatic aldehydes and α-ketoesters

A ruthenium-catalyzed asymmetric arylation of aliphatic aldehydes and α-ketoesters with arylboronic acids has been developed, giving chiral alkyl(aryl)methanols and α-hydroxy esters in good yields. The use of a chiral bidentate phosphoramidite ligand (Me-BIPAM) achieved excellent enantioselectivities.     

Ytterbium triflate-catalyzed conjugate addition of β-ketoesters to activated 1,4-naphthoquinones

An efficient procedure for the conjugate addition of various β-ketoesters to activated 1,4-naphthoquinones using a catalytic amount of Yb(OTf)₃ was developed. The tri-, tetra-, and pentacyclic adducts were obtained in very good to excellent yield. Cyclic β-ketoesters added smoothly to activated quinones when compared to their acyclic counterparts.     

One-pot synthesis of highly diversified tetrahydropyridines by tandem condensation of aldehydes,amines, and β-ketoesters

Silica-supported boron trifluoride (BF₃·SiO₂) was used as an efficient and reusable catalyst for the synthesis of highly diversified tetrahydropyridines by one-pot multicomponent reactions of amines and aldehydes with β-ketoester. This method proceeds through the intermolecular Mannich reaction followed by intramolecular Mannich reaction. The observed hydrogen bonding interaction was studied in detail with single crystal X-ray diffraction analysis and Etter’s graph. Finally, this method has the advantage of easy work-up, convenient, relatively short reaction times and the products were isolated with high yields.     

The asymmetric addition of phenylacetylene to aldehydes

Enantioselective formation of C-C bonds is an area of intense research.Among them, the asymmetric addition of alkynyl reagents to aldehydes is very useful for the synthesis of chiral secondary propargyl alcohols, which are very important building blocks for many chiral organic compounds, and the acetylene and hydroxyl founctional group of propargyl alcohol can be easily transfered into many other structures.1Recently, many significant chiral ligands have been disclosed.2 Here, we report our r…     

Base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes

We describe a convergent, base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes in a three-component process. The synthetic potential of this protocol was underscored by the synthesis of several symmetrical 1,3,5-triaryl-4-alkyl and 1,3,4,5-tetraryl substituted pyrazoles in a three-step sequence.     

High enantioselective Michael addition of malonates to β,γ-unsaturated α-ketoesters catalyzed by bifunctional thioureas

A highly enantioselective Michael addition of malonates to β,γ-unsaturated α-ketoesters was achieved using cinchona alkaloid-derived thioureas as the bifunctional catalyst. The corresponding Michael addition products were obtained in excellent yields (90–99%) and ee values (up to >99% ee) using a quinidine-derived thiourea as the catalyst under neat conditions. The opposite enantiomer may be obtained using a quinine- or cinchonidine-derived thiourea as the catalyst.     

Organocatalytic oxy-Michael addition of alcohols to α,β-unsaturated aldehydes

1,4-Addition of alcohols to α,β-unsaturated aldehydes was found to be efficiently promoted by biphenyldiamine-based catalyst 3 without formation of the acetals.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by 1,2,3,4-tetrahydroisoquinoline β-amino alcohol

<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions.     

Noscapine-derived β-amino alcohols as new organocatalysts for enantioselective addition of diethylzinc to aldehydes

In this paper, synthesis of two derivatives of noscapine and their application as organocatalysts in the asymmetric addition of diethylzinc to aromatic aldehydes is reported. The first catalyst (2) was synthesized by the reduction of lactone ring of noscapine to form the corresponding diol, and the second one (3) was prepared by tert-butyl dimethyl silylation of the primary hydroxyl group of 2. Excellent yields and high ees up to 95% were obtained by using 3 as the catalyst. To the best of our knowledge, this is the first report on the application of lactone ring opened noscapinoid compounds as organocatalysts in asymmetric reactions.     

Chiral bifunctional squaramide catalyzed asymmetric Michael addition of ethyl α-nitroacetate to β,γ-unsaturated α-ketoesters

We have developed an efficient bifunctional squaramide catalyst for the asymmetric Michael addition of ethyl α-nitroacetate to β,γ-unsaturated α-ketoesters. This organocatalytic asymmetric reaction provides convenient and valuable access to highly functionalized 2-nitro-5-oxo-3-arylhexanedioates in excellent yields with uniformly high levels of enantioselectivity (up to >99% ee) albeit with no diastereoselectivity. The resulting products could be conveniently transformed into 5-nitro-2-oxo-4-arylpentanoic acids without loss of enantiomeric excess via basic hydrolysis and the subsequent decarboxylation. This represents an example of in-direct, but efficient asymmetric conjugate addition of pyruvic acid to nitroolefins.     

Organocatalytic conjugate addition of 1-bromonitroalkanes to α,β-unsaturated aldehydes: synthesis of nitrocyclopropanes

A variety of secondary amines were studied as the catalyst in the conjugate addition of 1-bromonitromethane to α,β-unsaturated aldehydes. Proline was identified as the best catalyst for this reaction. MeOH/AcONa system was found to provide much better yields than CHCl₃/Et₃N system reported before. Good yields of nitrocyclopropane products were obtained with a variety of β-aryl acroleins. Several substituted 1-bromonitromethanes were also examined in the reaction. Both 1-bromonitroethane and 1-phenyl-1-bromonitromethane gave the corresponding nitrocyclopropanes in good yields. The diastereoselectivity of the reaction was strongly affected by the steric hindrance of 1-bromonitroalkanes.     

Asymmetric organocatalytic oxy-Michael addition of alcohols to α,β-unsaturated aldehydes

A 1,4-addition of alcohols to α,β-unsaturated aldehydes was found to be efficiently promoted by biphenyldiamine-based catalyst 3 without formation of the acetals. An asymmetric variant of this reaction has also been performed by designing a novel axially chiral organocatalyst (R)-10c.     

Chemistry, physico-chemistry and applications linked to biological activities of β-glucans

β-Glucans is the common name given to a group of chemically heterogeneous polysaccharides. They are long- or short-chain polymers of (1-->3)-β-linked glucose moieties which may be branched, with the branching chains linked to the backbone by a (1-->6)-β linkage. β-(1-->3)-Glucans are widely distributed in bacteria, algae, fungi and plants, where they are involved in cell wall structure and other biological function. β-Glucans have been shown to provide a remarkable range of health bene?ts, and are especially important against the two most common conventional causes of death in industrialized countries, i.e. cardiovascular diseases (where they promote healthy cholesterol and blood glucose levels) and cancer (where they enhance immune system functions). This Highlight provides a comprehensive and up-to-date commentary on β-glucans, their chemistry, physico-chemistry, functional role in immunological responses, and possible applications as therapeutic tools. In addition, we discuss the mechanism behind their health bene?ts, which are not yet fully understood.     

Two-carbon homologation of aldehydes and ketones to α,β-unsaturated aldehydes

Phosphonate reagents were developed for the two-carbon homologation of aldehydes or ketones to unbranched- or methyl-branched α,β-unsaturated aldehydes. The phosphonate reagents, diethyl methylformyl-2-phosphonate dimethylhydrazone and diethyl ethylformyl-2-phosphonate dimethylhydrazone, contained a protected aldehyde group instead of the usual ester group. A homologation cycle entailed condensation of the reagent with the starting aldehyde, followed by removal of the dimethylhydrazone protective group with a biphasic mixture of 1 M HCl and petroleum ether. This robust two-step process worked with a variety of aldehydes and ketones. Overall isolated yields of unsaturated aldehyde products ranged from 71% to 86% after the condensation and deprotection steps.     

An l-proline-based β-amino tertiary thiol: synthesis and use as a catalyst in the enantioselective addition of diethylzinc to aldehydes

Two independent routes for the synthesis of the novel β-amino tertiary thiol 1 have been developed. Utilisation of this thiol in the enantioselective addition of diethylzinc to aldehydes provided (R)-secondary alcohols in ees of up to 64%.     

Enantioselective addition of Et_2Zn to aldehydes catalyzed by chi-ral aliphatic β-amino alcohols

This paper describes the preparation of two new optically active aliphatic β-amino alcohols (R)-5,5-dimethyl-2-(dimethy-lamino)-1,1-diphenyl-1-hexanol (1a) and (S)-8,8-dimethyl-2-(dimethylamino)-1, 1-diphenyl-1-nonanol (1b). They were synthesized by methylation of the corresponding β-amino alcohols 2a and 2b. Compounds la and 1b catalyze the addition of diethylzinc to various aldehydes enantioselectively. The catalyst structure-enantioselectivity relationships were discussed.     

BINOL-phosphoric acid catalyzed asymmetric Mannich addition of β-ketoesters to indolenines generated in situ by DDQ

An asymmetric Mannich addition of β-ketoesters to indolenines that were generated in situ from 3-indolinone-2-carboxylates by DDQ has been developed using a catalytic amount of chiral BINOL-phosphoric acid. The corresponding chiral 3-indolinone-2-carboxylate derivatives were obtained in good yields with excellent ee (up to 99%). This is the first report on the enantioselective addition of β-ketoesters to indolenines using a chiral Brønsted acid.     

Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates

Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β'-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β'-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin(?)) in one step from the Michael adducts in high yields.