Catalytic Enantioselective Aldol Reaction Research Articles

Catalytic Enantioselective Aldol Reactions of Pyruvates as Nucleophiles with Chlorinated and Fluorinated Aldehydes and Ketones.

Reactions of pyruvates as nucleophiles under catalytic conditions are difficult to control without the use of enzymes as catalysts. Here, enantioselective aldol reactions of pyruvates with chlorinated and fluorinated aldehydes and ketones under organocatalytic conditions, in which pyruvates act as nucleophiles, are reported. Based on analyses of self-aldol reactions of pyruvates in the presence of model catalysts, catalysts of the desired cross aldol reactions were developed. Using the primary amine-derived catalyst, the desired aldol products, i.e., γ-chlorinated alkyl or γ-fluorinated alkyl group-substituted γ-hydroxy α-ketoesters, were obtained in good to high yields with high enantioselectivities.

Asymmetric Aldol Reaction of Alkenyl Esters with α-Keto Esters Catalyzed by Chiral Tin Alkoxides

AbstractA catalytic enantioselective aldol reaction of alkenyl esters with α-keto esters was achieved by using an (R)-BINOL-derived chiral tin dibromide possessing 4-t-butylphenyl groups at the 3- and 3′-positions as a chiral precatalyst in the presence of sodium methoxide and methanol. Optically active aldol products possessing a chiral tertiary carbon were diastereoselectively obtained with up to 92% ee and moderate to high yields, not only from cyclic alkenyl esters, but also from acyclic ones under the influence of the chiral tin methoxide generated in situ.

Chiral Silver Alkoxide Catalyzed Asymmetric Aldol Reaction of Alkenyl Esters with Isatins

AbstractA catalytic enantioselective aldol reaction of alkenyl esters with isatins was achieved using a DM-BINAP·AgOTf complex as the chiral precatalyst and N,N-diisopropylethylamine as the base precatalyst in the presence of methanol or 2,2,2-trifluoroethanol. Optically active 3-alkylated 3-hydroxy-2-oxindoles having up to 98% ee were diastereoselectively obtained in moderate to high yields not only from cyclic alkenyl esters but also from acyclic ones through the in situ generated chiral silver enolates.

Catalytic Enantioselective Aldol‐Type Reaction Using α‐Fluorinated Enolates

AbstractOptically active α‐fluoroalkyl substituted alcohols are widely present in drugs and pharmaceutically active compounds. Catalytic enantioselective aldol‐type reaction using fluorinated enolates constitutes a powerful method for the synthesis of α‐fluorinated β‐hydroxy carbonyl compounds, which are versatile building blocks to access α‐fluorinated alcohols bearing different functionalities through an array of transformations based on carbonyl group. This Focus Review summarizes recent achievements of the catalytic enantioselective aldol reactions using fluorinated enolates derived from five different types of precursors, discusses in detail the limitation of each method, and outlines synthetic opportunities still present.

Catalytic Enantioselective Aldol Reactions of Unprotected Carboxylic Acids under Phosphine Oxide Catalysis

AbstractThe first catalytic enantioselective aldol reaction of various unprotected carboxylic acids is described. In the presence of a chiral bis(phosphine oxide) as a Lewis base catalyst, carboxylic acids were activated with silicon tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or a ketone to produce β‐hydroxycarboxylic acids in high enantioselectivities of up to 92 % ee.

Catalytic Enantioselective Aldol Reactions of Unprotected Carboxylic Acids under Phosphine Oxide Catalysis.

The first catalytic enantioselective aldol reaction of various unprotected carboxylic acids is described. In the presence of a chiral bis(phosphine oxide) as a Lewis base catalyst, carboxylic acids were activated with silicon tetrachloride to form the corresponding bis(trichlorosilyl)enediolates in situ, which subsequently underwent an aldol reaction with an aldehyde or a ketone to produce β-hydroxycarboxylic acids in high enantioselectivities of up to 92 % ee.

Catalytic enantioselective aldol reactions.

Recent developments in catalytic asymmetric aldol reactions have been summarized. Enantioselective aldol reactions are important methods to synthesize β-hydroxy carbonyl compounds in optical pure form, and as such, numerous successful chiral catalysts were designed and applied for asymmetric aldol reactions. This review article is organized under the categories of: (1) catalytic enantioselective aldol reactions of preformed enolates, (2) catalytic enantioselective direct-type aldol reactions using chiral metal catalysts, (3) catalytic enantioselective direct-type aldol reactions using organocatalysts, (4) catalytic enantioselective aldol reactions in aqueous media. Examples of the aldol reactions that employ simple carbonyl compounds will be also the focus of this review.

Catalytic Enantioselective Synthesis of Chiral Isatin Derivatives by an Aldol Approach

A catalytic enantioselective aldol reaction of alkenyl esters with isatins was achieved using an (S)-BINOL-derived chiral tin dibromide possessing a 4-tert-butylphenyl group at 3- and 3′-positions as the chiral pre-catalyst in the presence of sodium methoxide and methanol. Optically active 3-alkylated 3-hydroxy-2-oxindoles having up to 98% ee were diastereoselectively obtained in high yields not only from cyclic alkenyl esters but also from acyclic ones under the influence of the in situ generated chiral tin bromide methoxide.

Direct aldol condensation reaction of ethyl diazoacetate with trifluoromethyl ketones

An efficient and direct aldol-type condensation of ethyl diazoacetate with trifluoromethyl ketones was developed in the presence of dialkyl zinc. A series of trifluoromethylated products were obtained in good to excellent yields (60–95%). A preliminary extension to a catalytic enantioselective aldol reaction of ethyl diazoacetate to trifluoromethyl ketones (up to 72% ee) is also described.

ChemInform Abstract: New Perspectives and Methodologies in Catalytic Enantioselective Aldol Reactions

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

(μ-Hydroxo)-platinum complex-catalyzed enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-1-(trimethylsilyloxy)propene in DMF

[(( R)-BINAP)Pt(μ-OH)] 2·2OTf catalyzed the enantioselective aldol reaction of aldehydes with 1-methoxy-2-methyl-(1-trimethylsilyloxy)propene at room temperature in dry DMF in high yields with enantioselectivity up to 92%. This is a versatile example of the catalytic enantioselective aldol reaction using a silyl ketene acetal promoted by (μ-hydroxo)-platinum complexes under mild conditions.

Catalytic Enantioselective Aldol Reaction to Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Dicationic ((−)-sparteine)palladium-catalyzed enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene, proceeding via a palladium enolate

A dicationic ((−)-sparteine)palladium complex underwent a superior catalytic enantioselective aldol reaction of aldehydes with 1-phenyl-1-trimethylsilyloxyethene performing satisfactorily, starting with ((−)-sparteine)PdCl 2 and AgSbF 6 as catalyst precursors (1 mol % loading) in the presence of 3 Å molecular sieves over the reaction.

Dirhodium(II) Tetrakis[N‐benzene‐fused phthaloyl‐(S)‐piperidinonate] as a Chiral Lewis Acid: Catalytic Enantioselective Aldol Reactions of Acetate‐Derived Silylketene Acetals and Aldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Catalytic Enantioselective Aldol Reaction to Ketones

An enantioselective aldol reaction between ketones and ketene silyl acetals is described using CuF-chiral phosphine as a catalyst. The key for high enantioselectivity was the development of a novel ligand derived from Taniaphos combined with the unique accelerative effect of PhBF3K. These conditions are applicable to various substrates such as aromatic, aliphatic, and heteroaromatic ketones. In the case of substituted nucleophiles, the reaction proceeds well. The diastereoselectivity is independent of ketene silyl acetal geometry. This is the first example of a catalytic enantio- and diastereoselective aldol reaction to ketones using ketene silyl acetals.

New Chiral Bis(diphenylphospholane) Ligands: Design, Synthesis, and Application to Catalytic Enantioselective Aldol Reaction to Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New chiral bis(diphenylphospholane) ligands: design, synthesis, and application to catalytic enantioselective aldol reaction to ketones

New chiral bidentate diphenylphospholanes were designed targeting a catalytic enantioselective aldol reaction to ketones. Ligands 5l and 5m having cis-2-butenyl and cyclopropyl groups at the linker part, respectively, were identified as effective chiral ligands for a CuF-catalyzed enantioselective aldol reaction to ketones. Catalysts prepared from CuF·3PPh 3·2EtOH and these ligands produced ketone aldol products with up to 66% ee, which is promising particularly for this extremely difficult and important catalytic enantioselective carbon–carbon bond forming reaction. The enantioselectivity was strongly dependent on the linker structure. Construction of a deep chiral pocket around the copper metal with stable bidentate chelation is the key to meaningful enantioinduction.

Dirhodium(II) Tetrakis[N-benzene-fused Phthaloyl-(S)-piperidinonate] as a Chiral Lewis Acid: Catalytic Enantioselective Aldol Reactions of Acetate-derived Silylketene Acetals and Aldehydes

A first example of chiral dirhodium(II) complex-catalyzed enantioselective Mukaiyama aldol reactions is described. The aldol addition reaction of methyl acetate-derived trimethylsilylketene acetal with specific aldehydes such as benzyloxyacetaldehyde and electron-poor aromatic aldehydes is effectively catalyzed by dirhodium(II) tetrakis[N-benzene-fused phthaloyl-(S)-piperidinonatel (la), providing silylated aldol adducts in up to 94% ee.

Recent Progress in Asymmetric Two‐Center Catalysis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Recent progress in asymmetric two-center catalysis.

Recent progress using two types of enantioselective two-center catalysts, Lewis acid-Brönsted base and Lewis acid-Lewis base bifunctional complexes, is described. The first part of this review discusses improvements in the syn-selective direct catalytic enantioselective aldol reaction and 1,4-addition reaction of a 2-hydroxyacetophenone derivative using a Zn-linked-BINOL complex. In the second part, we describe the development of catalysts displaying Lewis acidity and Lewis basicity in a catalytic enantioselective cyanosilylation of aldehydes and the logical extension to a tetrasubstituted carbon synthesis through a Reissert-type reaction and a cyanosilylation of ketones.