Enantioselective Direct Aldol Reaction Research Articles

Enantioselective Direct Aldol Reactions of Achiral Ketones with Racemic Enolizable α-Substituted Aldehydes: Scope and Limitations

Aldol reactions of racemic enolizable dioxolan-protected α-substituted-β-ketoaldehydes with representative achiral ketones catalyzed by proline or 5-(2-pyrrolidine-2-yl)-1H-tetrazole in wet DMSO proceed with dynamic kinetic resolution (or via DYKAT with an α-substituted-β-alkoxyaldehyde) to give adducts with high dr and ee.

Organocatalytic Enantioselective Direct Aldol Reaction in Aqueous Media Catalyzed by a Bifunctional Diamine Catalyst

Organocatalytic direct asymmetric anti-aldol reaction was developed in aqueous medium using a BINOL-derived diamine/protic acid bifunctional catalyst. The catalytic protocol could offer the opportunity to access anti-aldol products with high level of enantioselectivities with moderate diastereoselectivities.

ChemInform Abstract: Thiazolidine‐Based Organocatalysts for a Highly Enantioselective Direct Aldol Reaction.

AbstractThe new organocatalysts exhibit high performance in asymmetric aldol reaction and Michael reaction in an aqueous medium.

ChemInform Abstract: The Role of Double Hydrogen Bonds in Asymmetric Direct Aldol Reactions Catalyzed by Amino Amide Derivatives.

AbstractReview: [101 refs.]

ChemInform Abstract: Solvent‐Free Direct Enantioselective Aldol Reaction Using Polystyrene‐Supported N‐Sulfonyl‐(Ra)‐binam‐D‐prolinamide as a Catalyst.

AbstractPolystyrene‐supported binam‐prolinamide (PSBP) is used as catalyst in the aldol reaction between several ketones and aldehydes under solvent‐free or aqueous conditions affording the corresponding aldol product in high regio‐, diastereo, and enantioselectivities.

One-step, efficient synthesis of combined threonine–surfactant organocatalysts for the highly enantioselective direct aldol reactions of cyclic ketones with aromatic aldehydes in the presence of water

In this work, a new class of organocatalysts have been designed and synthesized in one step by a rational combination of threonine with acyl chlorides at room temperature in trifluoroacetic acid to make a series of novel combined threonine-surfactant organocatalysts readily available on a large-scale. No protecting groups or chromatographic techniques are involved in the procedures, while certain combined threonine-surfactant organocatalysts mediate the direct aldol reactions of cyclic ketones with aromatic aldehydes to provide the aldol products in good yields with enantioselectivities of up to 99%.

Thiazolidine-based organocatalysts for a highly enantioselective direct aldol reaction

A set of enantiopure thiazolidine-based organocatalysts have been synthesized from l-cysteine, in a straightforward manner allowing numerous structural variations. In particular, organocatalyst 3a exhibits the highest catalytic performance working in an aqueous medium. It catalyzed the direct catalytic asymmetric intermolecular aldol reaction between unmodified ketones and an aldehyde with excellent stereocontrol and furnished the corresponding aldol products in up to 99% ee. Compound 3a also showed excellent asymmetric catalytic activity in the asymmetric Michael reaction (up to 99% ee).

Novel Prolinamide Organocatalysts Based on Calix[4]arene Scaffold for the Enantioselective Direct Aldol Reaction

A series of novel prolinamide organocatalysts based on calix[4]arene scaffold have been developed to catalyze the direct asymmetric aldol reaction of aromatic aldehydes and cyclohexanone. Under the optimal condition, high isolated yields (up to > 99%) and enantioselectivities (up to 97% ee), and moderate diastereoselectivities (up to 85/15) were obtained.

ChemInform Abstract: Highly Diastereo‐ and Enantioselective Direct Aldol Reactions by 4‐tert‐Butyldimethylsiloxy‐Substituted Organocatalysts Derived from N‐Prolylsulfonamides in Water.

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.

Asymmetric Direct Vinylogous Aldol Reaction of Furanone Derivatives Catalyzed by an Axially Chiral Guanidine Base

Ace of Base: The first highly enantioselective direct vinylogous aldol reaction of dihalogenated or α-thio-substituted furanones with aldehydes utilizes an axially chiral guanidine base catalyst. The method provides facile access to enantioenriched γ-substituted butenolides.

Enantioselective Direct Aldol Reactions Using Bifunctional Catalysis

Enantioselective Direct Aldol Reactions Using Bifunctional Catalysis

Solvent-free direct enantioselective aldol reaction using polystyrene-supported N-sulfonyl-(Ra)-binam-d-prolinamide as a catalyst

The immobilization of N-sulfonyl-(Ra)-binam-D-prolinamide using polystyrene as a support allows the recovery of an efficient catalytic system for the enantioselective direct aldol reaction between different ketones and aldehydes under solvent-free or aqueous conditions. The polystyrene-supported N-sulfonyl-(Ra)-binam-D-prolinamide catalyst in combination with benzoic acid showed similar results to those obtained with unsupported N-tosyl-binam-derived prolinamide under similar reaction conditions. The aldol products were obtained at room temperature and using only 2 equivalents of the ketone with high yields, regio-, diastereo- and enantioselectivities. The aldol reaction between aldehydes can also be performed under these reaction conditions with moderate results. The recovered catalyst can be reused up to six times without having a detrimental effect on the achieved results.

The role of double hydrogen bonds in asymmetric direct aldol reactions catalyzed by amino amide derivatives

The double hydrogen bonding activation of carbonyl functionality has been a general strategy for the design of amino amide organocatalysts for highly enantioselective direct aldol reactions of various ketones with aldehydes conducted in either organic solvents or aqueous media. Moreover, this concept may suggest an activation mode to create new catalysts for other related asymmetric transformations.

ChemInform Abstract: Highly Enantioselective Direct Aldol Reactions Catalyzed by Proline Derivatives Based on a Calix[4]arene Scaffold in the Presence of Water.

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.

Proline−β3-Amino-Ester Dipeptides as Efficient Catalysts for Enantioselective Direct Aldol Reaction in Aqueous Medium

Dipeptides obtained from l-proline and beta(3)-l-amino acids are reported to catalyze enantioselective direct aldol reaction in aqueous medium, leading to significant anti:syn diastereomeric ratios and enantiomeric excesses. The simple introduction of a polar substituent at the C-2 position of the beta(3)-l-amino acid was also found to enhance appreciably both diastereo- and enantioselectivity of the catalyst.

Chiral Catalysts Dually Functionalized with Amino Acid and Zn2+ Complex Components for Enantioselective Direct Aldol Reactions Inspired by Natural Aldolases: Design, Synthesis, Complexation Properties, Catalytic Activities, and Mechanistic Study

Aldolases are enzymes that catalyze stereospecific aldol reactions in a reversible manner. Naturally occurring aldolases include class I aldolases, which catalyze aldol reactions via enamine intermediates, and class II aldolases, in which Zn(2+) enolates of substrates react with acceptor aldehydes. In this work, Zn(2+) complexes of L-prolyl-pendant[15]aneN(5) (ZnL(3)), L-prolyl-pendant[12]aneN(4) (ZnL(4)), and L-valyl-pendant[12]aneN(4) (ZnL(5)) were designed and synthesized for use as chiral catalysts for enantioselective aldol reactions. The complexation constants for L(3) to L(5) with Zn(2+) [logK(s)(ZnL)] were determined to be 14.1 (for ZnL(3)), 7.6 (for ZnL(4)), and 9.6 (for ZnL(5)), indicating that ZnL(3) is more stable than ZnL(4) and ZnL(5). The deprotonation constants of Zn(2+)-bound water [pK(a)(ZnL) values] for ZnL(3), ZnL(4), and ZnL(5) were calculated to be 9.2 (for ZnL(3)), 8.2 (for ZnL(4)), and 8.6 (for ZnL(5)), suggesting that the Zn(2+) ions in ZnL(3) is a less acidic Lewis acid than in ZnL(4) and ZnL(5). These values also indicated that the amino groups on the side chains weakly coordinate to Zn(2+). We carried out aldol reactions between acetone and 2-chlorobenzaldehyde and other aldehydes in the presence of catalytic amounts of the chiral Zn(2+) complexes in acetone/H(2)O at 25 and 37 degrees C. Whereas ZnL(3) yielded the aldol product in 43% yield and 1% ee (R), ZnL(4) and ZnL(5) afforded good chemical yields and high enantioselectivities of up to 89% ee (R). UV titrations of proline and ZnL(4) with acetylacetone (acac) in DMSO/H(2)O (1:2) indicate that ZnL(4) facilitates the formation of the ZnL(4)(acac)(-) complex (K(app)=2.1x10(2) M(-1)), whereas L-proline forms a Schiff base with acac with a very small equilibrium constant. These results suggest that the amino acid components and the Zn(2+) ions in ZnL(4) and ZnL(5) function in a cooperative manner to generate the Zn(2+)-enolate of acetone, thus permitting efficient enantioselective C-C bond formation with aldehydes.

Highly diastereo- and enantioselective direct aldol reactions by 4- tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water

A new set of 4- tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamide has been designed and proved to be effective in catalyzing the direct aldol reactions of cyclic ketones with a series of aromatic aldehydes. Furthermore, to the best of our knowledge, there are no reports on the aldol reaction generating the products in very good yields (>99%) and with excellent diastereoselectivities up to >99:1 and enantioselectivities up to >99% by using lower catalyst loadings (only 3 mol %), without using any additives in a large amount of water under mild conditions.

A Novel Proline‐Valinol Thioamide Small Organic Molecule for a Highly Enantioselective Direct Aldol Reaction

AbstractA new prolinethioamide compound 4, prepared from readily available natural amino acid L‐proline and amino alcohol L‐valinol, has been found to be an active catalyst for the direct aldol reaction of various aldehydes with acetone, cyclohexanone or cyclopentanone at 0 °C. Using only 2 mol% loading of this organocatalyst, the reaction could give high enantioselectivity with up to 96% enantiomeric excess for the reaction of 2‐nitrobenzaldehyde with acetone. And as for the cyclohexanone, the excellent diastereoselectivity (anti/syn: 99/1) and enantioselectivity (99% ee) could be achieved when reacted with 3‐nitrobenzaldehyde in water in the presence of this thioamide 4. This structurally simple catalyst is a highly efficient prolinethioamide derivative, and the terminal hydroxy group in this catalyst is a primary alcohol which is different from the previously reported prerequisite secondary or tertiary alcohol of prolinamides. Our results suggest a new strategy in the design of diversiform organic catalysts for direct asymmetric aldol reactions and related transformations.

ChemInform Abstract: Enantioselective Direct Aldol Reactions Catalyzed by Cinchonine‐Derived Prolinamides.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Enantioselective Direct Aldol Reactions Catalyzed by Proline Derivatives Based on a Calix[4]arene Scaffold in the Presence of Water

A series of proline-derived organocatalysts based on a calix[4]arene scaffold have been developed to catalyze direct aldol reactions in the presence of water. Under the optimal conditions, high yields (up to >99%), good enantioselectivities (up to >99% ee) and diastereoselectivities (up to 90:10) were obtained.