Organocatalyst For Asymmetric Aldol Reaction Research Articles

Polymer Supported Proline-Based Organocatalysts in Asymmetric Aldol Reactions: A Review

Abstract: The use of proline-based organocatalysts has acquired significant attention in organic synthesis, especially in enantioselective synthesis. Proline and its derivatives are proven to be quite effective chiral organocatalysts for a variety of transformations, including the aldol reaction, which is considered as one of the important C-C bond forming reactions in organic synthesis. The use of chiral organocatalysts has several advantages over its metal-mediated analogues. Subsequently, a large number of highly efficient proline-based organocatalysts, including polymer-supported chiral analogues, have been identified for aldol reaction. The use of polymer-supported organocatalysts exhibited remarkable stability under the reaction conditions and offered the best results, particularly in terms of its recyclability and reusability. These potential benefits along with their economic and green chemistry advantages have led to the search for many polymer-supported proline catalysts. In this review, recent developments in exploring various polymer immobilized proline- based chiral organocatalysts for asymmetric aldol reactions are described.

An investigation of chiral diamides as organocatalysts in asymmetric aldol reaction

AbstractSeven novel proline and 1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (THIQA) based diamides were synthesized successfully by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were performed by the reactions of aliphatic ketones and various aromatic aldehydes. Especially, (S)‐N‐((S)‐1‐(morpholinoamino)‐1‐oxo‐3‐phenylpropan‐2‐yl)pyrrolidine‐2‐carboxamide (9e) showed good catalytic activities in water at room temperature in the presence of benzoic acid cocatalyst. The enantioselectivities were upto 89.6%, the diastereomeric ratios were upto 92/8, and yields were upto 97.3%. This catalyst showed its best catalytic activities in water; this is also an important contribution to green chemistry requirements.

Chiral Imidazolium Prolinate Salts as Efficient Synzymatic Organocatalysts for the Asymmetric Aldol Reaction.

Chiral imidazolium l-prolinate salts, providing a complex network of supramolecular interaction in a chiral environment, have been studied as synzymatic catalytic systems. They are demonstrated to be green and efficient chiral organocatalysts for direct asymmetric aldol reactions at room temperature. The corresponding aldol products were obtained with moderate to good enantioselectivities. The influence of the presence of chirality in both the imidazolium cation and the prolinate anion on the transfer of chirality from the organocatalyst to the aldol product has been studied. Moreover, interesting match/mismatch situations have been observed regarding configuration of chirality of the two components through the analysis of results for organocatalysts derived from both enantiomers of prolinate (R/S) and the trans/cis isomers for the chiral fragment of the cation. This is associated with differences in the corresponding reaction rates but also to the different tendencies for the formation of aggregates, as evidenced by nonlinear effects studies (NLE). Excellent activities, selectivities, and enantioselectivities could be achieved by an appropriate selection of the structural elements at the cation and anion.

Pro-Phe Derivatives as Organocatalysts in Asymmetric Aldol Reaction

Pro-Phe Derivatives as Organocatalysts in Asymmetric Aldol Reaction

Pro-Phe Derivatives as Organocatalysts in Asymmetric Aldol Reaction

The aldol reaction which is the most important one among the C-C bond forming reactions, is widely used by synthetic organic chemists to obtain β-hydroxycarbonyl compounds which are important starting components for biologically active compounds in optically pure form. In this research, five Pro-Phe derivatives were synthesized by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were investigated. The catalytic activity studies were performed with aliphatic ketones and various aromatic aldehydes. Especially, (S)- methyl 3-mercapto-2-((S)-3-phenyl-2-((S)-pyrrolidine-2-carboxamido)propanamido)propanoate showed good catalytic activities in water at 0oC in the presence of p-nitrobenzoic acid cocatalyst. The enantioselectivities were up to 90.4%, the diastereomeric ratios were up to 97/3 and yields were 99%. The results showed that these organocatalysts were promising organocatalysts for aldol reaction. Besides, this catalyst showed its best catalytic activities in water which is also an important contribution to green chemistry requirements.

Synthesis of New Di- and Triamides as Potential Organocatalysts for Asymmetric Aldol Reaction in Water

New di- or triamide organocatalysts derived from (L)-proline were synthesized and successfully used in the direct asymmetric aldol reaction of aliphatic ketones and aromatic aldehydes in water at 0oC in the presence of benzoic acid as co-catalyst. (S)-methyl-2-((S)-3-hydroxy-2-((S)-3-pyrrolidine-2-carboxamido)propanamido)-3-phenylpropanoate (7c) as organocatalyst showed best results under these reaction conditions, and good diastereoselectivities (up to 99%), enantioselectivities (up to 98%) and yields (up to 91%) were observed.

L-proline functionalized pH-responsive copolymers as supported organocatalysts for asymmetric aldol reaction in water

pH-Responsive copolymers with reversible transformation ability have been investigated as new effective carriers for L-proline to catalyze asymmetric aldol reaction in water. A series of block copolymers of mPEG-b-P(DEAx-co-L-ProlAy) (mPEG-PDL) bearing L-proline catalytic sites and pH-responsive poly (diethylaminoethyl methacrylate) (PDEA) segments were synthesized by the reversible addition-fragmentation chain transfer (RAFT) polymerization in the presence of methyl polyethylene glycol (mPEG) trithiocarbonate macro-RAFT agent. The pH-induced self-assembly behaviors of three copolymer catalysts with different contents of PDEA were investigated via the combination of UV–visible spectrometer (UV–vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM). Catalytic activity and stereoselectivity of these copolymer catalysts were evaluated by direct asymmetric aldol reaction of p-nitrobenzaldehyde and cyclohexanone in water. The results indicated that catalytic activity and stereoselectivity effected by the pH value of aqueous solution and the structures of copolymer catalyst assemblies. mPEG-PDL-2 give the aldol product with high conv., yield, anti/syn, and ee (92%, 91%, 92/8, 96%), respectively at pH 7.0. Furthermore, these pH-responsive copolymers supported L-proline are easily recycled by a reversible phase transition.

Cover Feature: Practical Synthesis of High‐Performance Amino Tf‐Amide Organocatalysts for Asymmetric Aldol Reactions (Asian J. Org. Chem. 2/2020)

The cover art depicts the direct asymmetric aldol reactions of cycloalkanones and substituted benzaldehydes catalyzed by a secondary-amino aromatic Tf-amide organocatalyst, affording the corresponding aldol adducts in good yield with good to excellent anti-diastereo- and enantioselectivity. The catalyst efficiently “lightens” the diastereo- and enantioselective transformation. The art shows a sky lantern, known as Kongming Light, which is used as a wishing lamp in the traditional Chinese Festivals, such as the Lantern Festival and Mid Autumn Festival. More information can be found in the Communication by Yan Liu, Keiji Maruoka et al. on page 206 in Issue 2, 2020 (DOI: 10.1002/ajoc.201900730).

Practical Synthesis of High‐Performance Amino Tf‐Amide Organocatalysts for Asymmetric Aldol Reactions

AbstractA type of optically pure secondary‐amino aromatic Tf‐amide organocatalysts can be easily prepared from commercially available L‐hydroxyproline. The chemical behavior of these organocatalysts was investigated by the application to asymmetric aldol reactions. Among these, catalyst 2 a efficiently catalyzed direct asymmetric aldol reactions of cycloalkanones and substituted benzaldehydes, which afforded the corresponding aldol adducts in good yield with good to excellent anti‐diastereo and enantioselectivity.

Reusable shuttles for exchangeable functional cargos: Reversibly assembled, magnetically powered organocatalysts for asymmetric aldol reactions

A supramolecular approach has been followed to support adamantyl substituted proline organocatalysts onto the surface of magnetite nanoparticles decorated with a β-cyclodextrin motif. The resulting magnetic nanoparticles (ca. ∼10 nm diameter) were used as modular, magnetically recyclable catalysts in the asymmetric aldol reaction of aromatic aldehydes with cyclic ketones in water. The catalytic assemblies can be easily dismantled in organic media, and the recovered nanoparticles (magnetically powered chemical shuttles) re-complexed with another suitably substituted catalytic unit (replaceable functional cargo).

Trifluoromethylated-Imidazolines as Efficient Organocatalyst for Asymmetric Aldol Reaction of Hydroxyacetone with Aldehydes

Trifluoromethylated-Imidazolines as Efficient Organocatalyst for Asymmetric Aldol Reaction of Hydroxyacetone with Aldehydes

Unnatural tripeptide as highly enantioselective organocatalyst for asymmetric aldol reaction of isatins

The development of unnatural tripeptides as highly enantioselective organocatalysts for the asymmetric aldol reaction of isatins was achieved. H-Pro-Gly-d-Ala-OH with the d-alanine residue as the C-terminal amino acid residue expressed the best enantioselectivity. The H-Pro-Gly-d-Ala-OH-catalyzed reaction of isatins gave various aldol adducts with up to 93% yield and up to 97% ee. Investigation of the transition state via DFT calculation revealed that high optical purity was realized by the d-alanine controlled steric environment.

Combining prolinamides with 2-pyrrolidinone: Novel organocatalysts for the asymmetric aldol reaction

Peptides and especially prolinamides have been identified as excellent organocatalysts for the aldol reaction. The combination of prolinamides with derivatives bearing the 2-pyrrolidinone scaffold, deriving from pyroglutamic acid, led to the identification of novel organocatalysts for the intermolecular asymmetric aldol reaction. The new hybrids were tested both in organic and aqueous media. Among the compounds tested, 22 afforded the best results in petroleum ether, while 25 afforded the products in brine in high yields and selectivities. Then, various ketones and aldehydes were utilized and the products of the aldol reaction were obtained in high yields (up to 100%) with excellent diastereo- (up to 97:3 dr) and enantioselectivities (up to 99% ee).

(2S,4R)-Hyp-(S)-Phe-OMe dipeptide supported on imidazolium tagged molecules as recoverable organocatalysts for asymmetric aldol reactions using water as reaction medium

Four novel chiral imidazolium tagged molecules derived from dipeptide (2S,4R)-Hyp-(S)-Phe-OMe were prepared and evaluated as organocatalysts in the asymmetric aldol reaction using water as solvent. It was found that catalysts incorporating the hexanoyl linker are active down to 5 mol% and afford aldol products with up to 94% yield, up to 98:2 dr and up to 97:3 er. This chiral imidazolium catalyst was reused up to 6 times without any loss in the stereoselectivity of asymmetric aldol reactions. By contrast, organocatalysts containing an acetyl linker proved to be highly unstable in protic solvents, and for that reason they could not be recovered and reused.

Towards Sustainable Amino Acid Derived Organocatalysts for Asymmetric syn‐Aldol Reactions

The undesirable side‐processes responsible for the fast deactivation of primary amino acid derived organocatalysts in asymmetric aldol reactions are identified. A new ionic‐liquid‐supported (S)‐valine‐/(S)‐α,α‐diphenylserinol‐derived catalyst (9) is designed on the basis of these results and exhibits much better recyclability in asymmetric syn‐aldol reactions between hydroxyacetone and aldehydes. Furthermore, this catalyst appeared to be useful for the stereoselective synthesis of the naturally occurring 1(3H)‐isobenzofuran‐1‐one scaffold through an asymmetric syn‐aldol/lactonization cascade reaction.

Monofunctional primary amine: A new class of organocatalyst for asymmetric Aldol reaction

A new class of organocatalysts involving a primary amine as the only functional group is developed for catalytic asymmetric aldol reaction of cyclohexanone/cyclopentanone with various aryl aldehydes in the presence of benzoic acid as an additive at −10∘C. In an unexpected observation, the primary amine catalyzed reactions gave excellent yield and good to excellent stereoselectivity, while secondary amines were found to have little or no reactivity under similar reaction conditions. A new class of aminocatalysts with a primary amine as the only catalytically active functional group was developed for catalytic asymmetric aldol reaction of cyclohexanone/cyclopentanone with various aryl aldehydes in the presence of benzoic acid as an additive at -10oC under neat conditions.

Carane amino alcohols as organocatalysts in asymmetric aldol reaction of isatin with acetone

Carane-derived β-amino alcohols with amino and hydroxy groups at positions 3 and 4 differing in their mutual arrangement and configuration were synthesized. Their application as organocatalysts in the asymmetric aldol reaction of isatin with acetone allowed one to obtain adducts with up to 84% enantiomeric excess.

Ionic liquid supported 4-HO-Pro-Val derived organocatalysts for asymmetric aldol reactions in the presence of water

Novel (4 R )-HO-(2 S )-Pro-( S )-Val derivative tagged to 1-methylimidazolium cation and P F 6 ¯ anion efficiently catalyzes asymmetric aldol reactions of cyclic ketones with aromatic aldehydes in aqueous environment to afford the corresponding aldols in high yield with moderate to high anti -diastereo- ( dr up to 99: 1) and enantioselectivity (up to 98% ee ). The catalyst was recycled 9 times in the same reaction without any decrease in selectivity values.

Optically Active Helical Polyacetylene Bearing Ferrocenyl Amino-Acid Derivative in Pendants. Preparation and Application as Chiral Organocatalyst for Asymmetric Aldol Reaction

The article reports a novel type of helical polymer-based chiral catalyst for catalyzing asymmetric aldol reactions. Chiral acetylenic monomers containing ferrocenyl amino-acid derivative substituent were synthesized for the first time and structurally identified. The investigated amino acids include alanine and threonine enantiomers. The obtained monomers separately underwent solution homopolymerization and copolymerization with an achirally substituted acetylene monomer in the presence of [Rh(nbd)Cl]2 and Et3N. Circular dichroism and UV–vis absorption spectra demonstrated that the copolymer chains adopted predominantly one-handed helices, endowing the copolymers with optical activity. The resulting (co)polymers were further used to catalyze aldol reaction between cyclohexanone and p-nitrobenzaldehyde. Only threonine-derived copolymers efficiently catalyzed the aldol reaction. A remarkable yield (up to 90%) and enantiomeric excess (up to 93%) were obtained. A synergic effect between the helical structure...

A Gold-NP-Supported Organocatalyst for Asymmetric Aldol Reactions

A Gold-NP-Supported Organocatalyst for Asymmetric Aldol Reactions