Enantioselective Direct Aldol Reaction Research Articles

Prolinamide and Prolinamide Tagged with Ionic Liquid Intercalated in Bentonite Clay, a Recyclable Catalyst for Asymmetric Aldol Reactions

AbstractThe imidazolium‐based chiral ionic liquids containing prolinamide moiety and prolinamide were intercalated in bentonite clay and evaluated in asymmetric aldol reactions of aromatic aldehydes or isatins with acetone or cyclohexanone. The 10 mol% of chiral ionic liquid having S‐phenylethylamine moiety 2 a catalyzed the direct enantioselective aldol reaction of isatins and acetone in i‐PrOH at −20 °C and afforded the corresponding 3‐alkyl‐3‐hydroxy indolin‐2‐ones in 72–98 % yields and 37–80 % ee's. The prolinamide intercalated in bentonite clay (0.125 g, 10 mol%) gave corresponding aldol products in 32–82 % yields and 38–91 % ee's. However, prolinamide intercalated bentonite clay was found to be less active as compared to chiral ionic liquids containing prolinamide. The prolinamide intercalated bentonite clay 8 was reused in four catalytic cycles, with a slight loss of activity and selectivity of the catalyst after the third recycling.

Enantioselective construction of β-hydroxy-α,α-disubstituted α-amino acid derivatives via direct aldol reaction of α-imino esters

The β-hydroxy-α,α-disubstituted α-amino acid is a valuable structural motif for research in the field of bioorganic chemistry and in the development of peptide drugs. This report describes the enantioselective direct-aldol reaction of α-imino esters with glyoxylate esters. We discovered that a catalytic amount of Co(OAc)2-pybox complex catalyzed the aldol reaction of salicylaldehyde-derived α-imino esters with benzyl glyoxylate in good yield and enantioselectivity. In addition, hydrolysis of the imine moiety of the aldol products followed by Boc protection of the resultant amino group gave the N-Boc-protected amino acid derivatives.

Catalytic enantioselective synthesis of chiral 4-hydroxy 4′-substituted pyrazolones by the vinylogous aldol reaction of pyrazole-4,5-diones with 3-alkylidene-2-oxindoles

Here, a bifunctional quinine-derived benzamide catalyzed direct enantioselective vinylogous aldol reaction between 3-alkylidene-2-oxindoles and pyrazole-4,5-diones has been developed.

One-step hydrothermal synthesis of chiral carbon dots with high asymmetric catalytic activity for an enantioselective direct aldol reaction.

Chiral carbon dots are prepared by a simple and one-step hydrothermal reaction at 180 °C for 2 h using citric acid and d-proline as precursors, which show high asymmetric catalytic activity for enantioselective direct aldol condensation. This work provides a hint for the simple preparation of heterogeneous chiral catalysts.

Synthesis of Bi‐functional Immobilized Polymer Catalysts via a Two‐step Radiation‐induced Graft Polymerization Process

AbstractHere, we designed and synthesized two types of bi‐functional immobilized polymer catalysts based on the prolineamide‐acid combination for direct enantioselective aldol reaction in flow systems. Conventional bi‐functional catalysts in which the two functions are present on the same graft polymer afforded up to 99 % yield and >99 % enantiomeric excess (ee) in a recirculating flow system. We also investigated bi‐functional catalysts in which the two functions are located on different graft polymers. We present a straightforward catalyst immobilization method that allows two different catalysts located on different graft polymers to be introduced separately onto the same polymer by conducting two successive steps of radiation‐induced graft polymerization process (RIGP). We confirmed that the graft polymers (grafted polycatalyst and polyacrylic acid chain) interact with each other to promote the aldol reaction with high conversion and ee. This design strategy may be superior to the conventional approach for synthesizing catalysts in which multiple functions interact.

Self-Assembled Bio-Organometallic Nanocatalysts for Highly Enantioselective Direct Aldol Reactions.

Supramolecular nanocatalysts were designed for asymmetric reactions through the self-assembly process of a bio-organometallic molecule, ferrocene-l-prolinamide (Fc-CO-NH-P). Fc-CO-NH-P could self-assemble into versatile nanostructures in water, including nanospheres, nanosheets, nanoflowers, and pieces. In particular, the self-assembled nanoflowers exhibited a superior specific surface area, high stability, and delicate three-dimensional (3D) chiral catalytic active sites. The nanoflowers could serve as heterogeneous catalysts with an excellent catalytic performance toward direct aldol reactions in aqueous solution, achieving both high yield (>99%) and stereoselectivity (anti/syn = 97:3, ee% >99%). This study proposed a significant strategy to fabricate supramolecular chiral catalysts, serving as a favorable template for designing new asymmetric catalysts.

Asymmetric Direct Aldol Reaction Catalyzed by (1R, 2R)-(+)-1, 2- Diammonium Cyclohexane-L-tartrate in Water

Background: A cheap and commercially available organocatalyst, (1R, 2R)-(+)-1, 2- diammonium cyclohexane-L-tartrate 1 was applied in direct aldol reaction in water. The organocatalyst 1 afforded aldol products from cyclohexanone and substituted aromatic aldehydes with high yield (up to 90%) and good stereoselectivity (up to 99% ee and up to 11.5:1 dr) in large volume of water (10 ml). Methods: The same aldol reaction when carried out in the presence of more expensive organocatalyst e.g. (1R, 2R)-(+)-1,2-diaminocyclohexane and 1,6-hexanediaoic acid as acid additive furnished the aldol products with only 20% yield, 2:1 anti/syn ratio and 92% ee. Results and Conclusion: In summary, we have applied a reasonably cheap and commercially available organocatalyst 1 for highly enantioselective direct aldol reaction in water at room temperature.

Noncovalent Catalysis for Enantioselective Direct Aldol Reaction of 3‐Acetylcoumarins to Pyrazole‐4,5‐diones

AbstractThe first catalytic enantioselective direct aldol reaction of 3‐acetylcoumarins to pyrazole‐4,5‐diones is reported and shown to proceed through noncovalent substrate activation by a quinine‐derived bifunctional tertiary amino‐amide as the catalyst. The densely functionalized products, consisting of an oxygen‐containing quaternary stereocenter and bearing two biologically relevant heterocycles, are generally obtained in high yields with moderate to excellent enantioselectivities.

Enantioselective Direct Aldol Reaction of α-Vinylated Thioamides

Key words copper catalysis - aldol reaction - aldehydes - thioamides - vinyl thioamides

Catalytic asymmetric direct aldol reactions of arylketones and arylaldehydes or reactive arylketones

It has been a long-standing challenge in organic chemistry to achieve highly efficient direct enantioselective aldol reactions of aromatic ketones and aldehydes under asymmetric catalytic conditions. Recently, with significant developments in metal-catalyzed and organocatalyzed enantioselective transformations, the goal of direct asymmetric aldol reactions of aromatic aldehydes or highly reactive aromatic ketones seems achievable; several improvements have been reported for chiral metal complex-based catalysts and organocatalysts. This article reviews the recent reports of catalytic asymmetric direct aldol reactions between arylketones and arylaldehydes or reactive arylketones.

Highly enantioselective asymmetric direct aldol reaction promoted by aziridine amides constructed on chiral terpene scaffold.

Optically pure, diastereomeric aziridine amides built on the chiral skeletons of camphor, fenchone, and menthone have proven to be highly efficient ligands for enantioselective asymmetric direct aldol reaction in the presence of water and zinc triflate. Desired products were formed in moderate to high chemical yields (up to 95%) and with enantiomeric excess up to 99%. The influence of the stereogenic centers located at the aziridine subunit on the stereochemical course of the reaction is discussed.

Chiral Calix[4]arenes-Bearing Prolinamide Functionality as Organocatalyst for Asymmetric Direct Aldol Reactions in Water

ABSTRACTThe chiral calix[4]arene derivative (6) bearing an L-prolinamido group has been designed and proved to be a water compatible efficient organocatalysts for a direct enantioselective aldol reaction. Compound 6 catalyzes the aldol reaction of cyclohexanone and a variety of aromatic aldehydes yielding anti-aldol products in high yield with enantioselectivities of up to 93% and diastereoselectivity of up to 95:5.

Polymerization of l-proline functionalized styrene and its catalytic performance as a supported organocatalyst for direct enantioselective aldol reaction

As an alternative approach to the graft modification of polymers to fabricate polymer-supported chiral organocatalysts in a bottom-up fashion, l-prolinamide functionalized polymers were prepared by general solution homopolymerization or copolymerization of l-proline functionalized styrene monomer in the presence of 1,4-divinylbenzene as the crosslinking agent. The catalytic performance of the as-prepared heterogeneous catalysts towards the direct enantioselective aldol reaction of ketones with a series of aromatic aldehydes was explored. Our findings indicate that the as-prepared heterogeneous catalysts can afford relevant aldol addition products with good yields (up to 96%), high diastereoselectivities (up to 8:92 dr) and excellent enantiomeric excess (up to 96%); they also exhibit good recyclability, retaining high yield and rate as well as good selectivity after several cycles.

ChemInform Abstract: Novel Efficient Bifunctional Calixarene Thiourea Organocatalysts: Synthesis and Application in the Direct Enantioselective Aldol Reactions.

AbstractA novel bifunctional calixarene thiourea CLXA is prepared and successfully applied as chiral catalyst for enantioselective aldol reactions of aryl aldehydes with acetone.

Multifunctional heterocyclic scaffolds for hybrid Lewis acid/Lewis base catalysis of carbon–carbon bond formation

Several new classes of hybrid catalysts have been synthesized by tethering heterocyclic metal (Lewis acid) chelating scaffolds to several different amines capable of facilitating enamine catalysis. Oxazole, thiazole, and imidazole-based chiral precatalysts were prepared in several steps from amino acid starting materials, and these were combined with a variety of metal Lewis acids for potential use as catalysts for various carbon–carbon bond formations. Air- and moisture-tolerant catalysts for enantioselective direct aldol reactions with activated benzaldehyde acceptors were identified, with optimal results obtained with proline-derived oxazole–carboxamide precatalysts combined with Zn(OTf)2 or lanthanide (III) salts. Control studies support the hypothesis that these act as unimolecular hybrid catalysts for the aldol reaction of propionaldehyde and 4-nitrobenzaldehyde.

Design and Synthesis of Oxazoline-Based Scaffolds for Hybrid Lewis Acid/Lewis Base Catalysis of Carbon–Carbon Bond Formation

A new class of hybrid Lewis acid/Lewis base catalysts has been designed and prepared with an initial objective of promoting stereoselective direct aldol reactions. Several scaffolds were synthesized that contain amine moieties capable of enamine catalysis, connected to heterocyclic metal-chelating sections composed of an oxazole–oxazoline or thiazole–oxazoline. Early screening results have identified oxa­zole–oxazoline-based systems capable of promoting a highly diastereo- and enantioselective direct aldol reaction of propionaldehyde with 4-nitrobenzaldehyde, when combined with Lewis acids such as zinc triflate.

ChemInform Abstract: Enantioselective Direct Aldol Reactions Promoted by Phosphine Oxide Aziridinyl Phosphonate Organocatalysts.

AbstractThe phosphonate POAP is tested as a chiral catalyst in the aldol reaction of cyclohexanone with aldehydes (II), however, the yield, diastereoselectivity, and enantioselectivity are only low to moderate.

Novel efficient bifunctional calixarene thiourea organocatalysts: synthesis and application in the direct enantioselective aldol reactions

Novel efficient bifunctional calixarene thiourea organocatalysts have been designed as efficient organocatalysts for direct asymmetric aldol reactions between acetone and aromatic aldehydes. The reactions generated the corresponding products in satisfactory isolated yields (up to 96%) and with excellent enantiomeric excesses (up to 99%) in the presence of catalyst (10mol %).

ChemInform Abstract: Phosphine Oxide Catalyzed, Tetrachlorosilane‐Mediated Enantioselective Direct Aldol Reactions of Thioesters.

AbstractThe title reaction between aryl substituted thioesters and aryl or hetaryl esters provides the corresponding β‐hydroxy thioesters in moderate yield, with no to excellent diastereomeric and moderate to high enantioselectivity.

Enantioselective direct aldol reactions promoted by phosphine oxide aziridinyl phosphonate organocatalysts

A series of phosphine oxide based chiral Lewis bases were screened as organocatalysts for silicon tetrachloride mediated direct asymmetric aldol reactions between cyclohexanone and various aromatic aldehydes. One of the phosphine oxide-aziridinyl phosphonate POAP-A Lewis bases formed the aldol products in up to 75% yield and with 65% ee.