Aldol Reactions Of Ketones Research Articles

Synthesis and application of triptycene based oligomers for the stereoselective aldol reaction of isatin and ketones

Novel triptycene derived oligomers (TOL1, TOL2 and TOL3) with multiple metal-coordinating sites have been synthesized in high yields using a three-component one-pot synthetic protocol and were characterized by various analytical tools such as FT-IR, solid state 13C NMR, GPC and FESEM. The GPC analysis revealed TOLs as oligomers with 8-10 repeating units. The catalytic applications of these oligomers were investigated for the stereoselective synthesis of 3-hydroxy-2-oxindoles via aldol reaction of isatin with ketones by the in-situ complexation of the oligomers with Cobalt metal. All the tested reactions worked well to generate the corresponding products in excellent yields with good diastereo-selectivities.

Visible-light-driven asymmetric aldol reaction of ketones and glycinates via synergistic Lewis acid/photoredox catalysis.

Visible-light-driven direct asymmetric α-C(sp3)-H bond functionalization of glycinate provides a direct and efficient route for the synthesis of diverse optically enriched α-amino acid derivatives. However, asymmetric coupling between glycinate radical species and ketones faces significant challenges, including competitive pathways, mutable intermediates, as well as congested stereogenic centers. Herein, we disclose the first example for the asymmetric photocatalytic synthesis of a diverse array of β-diaryl-β-hydroxy-α-amino acetate derivatives from glycinates and heteroaryl ketones through the synergistic catalysis of achiral iridium photoredox catalyst and chiral lanthanide Lewis acid catalysts. The enantioselective radical addition pathway is supported by spectroscopic experiments, control experiments and DFT calculations.

Highly enantioselective hydroxymethylation of unmodified α-substituted aryl ketones in water.

Catalytic asymmetric direct-type aldol reactions of ketones with aldehydes are a perennial puzzle for organic chemists. Notwithstanding the emergence of a myriad of chiral catalysts to address the inherent reversibility of the aldol products, a general method to access acyclic α-chiral ketones from prochiral aryl ketones has remained an unmet synthetic challenge. The approach outlined herein is fundamentally different to that used in conventional catalysis, which typically commences with an α-proton abstraction by a Brønsted base. The use of a chiral 2,2'-bipyridine scandium complex enabled the hydroxymethylation of propiophenone to be run under base-free conditions, which avails effectual suppression of hydrolytic deactivation of the Lewis acid catalyst. Intriguingly, the use of water as a reaction medium had an overriding effect on the progress of the reaction. The sagacious selection of sodium dodecyl sulfate and lithium dodecyl sulfate as surfactants allowed a variety of propiophenone derivatives to react in a highly enantioselective manner.

Highly asymmetric aldol reaction of isatins and ketones catalyzed by chiral bifunctional primary-amine organocatalyst on water.

Herein, we have reported an environmentally friendly asymmetric aldol reaction between isatins and ketones catalyzed by double-hydrogen-bonded primary amine organocatalysts on water under mild conditions. Enantioenriched 3-hydroxy-2-oxindoles were obtained in high yields (up to 99%) and excellent stereoselectivities (up to 99 : 1 dr and 99% ee) under optimal conditions. Furthermore, the model reaction involving isatin and cyclohexanone was successfully scaled to 10 mmol with no reduction in yield or stereoselectivity. In addition, the catalyst was recovered via simple filtration and was subsequently reused on water, which highlights its good application potential.

New boro amino amide organocatalysts for asymmetric cross aldol reaction of ketones with carbonyl compounds.

Distinct types of new boron fused primary amino amide organocatalysts were designed and synthesized from commercially available amino acids. Their catalytic activities were investigated in asymmetric crossed aldol reaction of ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good chemical yields, moderate diastereoselectivity and good to excellent enantioselectivities (up to 94% yields, up to 90 : 10 dr, up to 94% ee).

Frontispiece: Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis

Organocatalysis In their Communication on page 20166, Guoqing Zhao, Baoguo Zhao et al. describe a highly efficient asymmetric biomimetic aldol reaction of glycinates and trifluoromethyl ketones via carbonyl catalysis.

Frontispiz: Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis

Organokatalyse In der Zuschrift auf S. 20328 beschreiben Guoqing Zhao, Baoguo Zhao et al. eine hoch effiziente asymmetrische biomimetische Aldolreaktion von Glycinaten und Trifluormethylketonen mittels Carbonyl-Katalyse.

Proline and 1-(2-(benzoxazole-2-yl)phenyl)-3-phenylthiourea supramolecular organocatalyst in asymmetric aldol reactions

In this work we report the (S)-proline-thiourea 1 host–guest complex as an efficient catalyst in the enantioselective aldol rection of ketones with aldehydes. This host–guest complex performs well at 0 °C, in a non-polar solvent, such as toluene, or under solvent-less conditions affording high yields (75%-86%), enantioselectivities (er > 87%) and diastereoselectivities (ds > 92%) in the asymmetric aldol reaction of ketones with aldehydes.

Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis

AbstractThe direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β‐hydroxy‐α‐amino‐acid derivatives. But it is not easy to realize the transformation due to the disruption of the reactive NH2 group of glycinates. Inspired by the enzymatic aldol reaction of glycine, we successfully developed an asymmetric aldol reaction of glycinate 5 and trifluoromethyl ketones 4 with 0.1–0.0033 mol % of chiral N‐methyl pyridoxal 7 a as the catalyst, producing chiral β‐trifluoromethyl‐β‐hydroxy‐α‐amino‐acid esters 6 in 55–82 % yields (for the syn‐diastereomers) with up to >20:1 dr and 99 % ee under very mild conditions. The reaction proceeds via a catalytic cycle similar to the enzymatic aldol reaction of glycine. Pyridoxal catalyst 7 a activates both reactants at the same time and brings them together in a specific spatial orientation, accounting for the high efficiency as well as excellent diastereo‐ and enantioselectivities.

Efficient Asymmetric Biomimetic Aldol Reaction of Glycinates and Trifluoromethyl Ketones by Carbonyl Catalysis.

The direct asymmetric aldol reaction of glycinates represents an intriguing and straightforward strategy to make biologically significant chiral β-hydroxy-α-amino-acid derivatives. But it is not easy to realize the transformation due to the disruption of the reactive NH2 group of glycinates. Inspired by the enzymatic aldol reaction of glycine, we successfully developed an asymmetric aldol reaction of glycinate 5 and trifluoromethyl ketones 4 with 0.1-0.0033 mol % of chiral N-methyl pyridoxal 7 a as the catalyst, producing chiral β-trifluoromethyl-β-hydroxy-α-amino-acid esters 6 in 55-82 % yields (for the syn-diastereomers) with up to >20:1 dr and 99 % ee under very mild conditions. The reaction proceeds via a catalytic cycle similar to the enzymatic aldol reaction of glycine. Pyridoxal catalyst 7 a activates both reactants at the same time and brings them together in a specific spatial orientation, accounting for the high efficiency as well as excellent diastereo- and enantioselectivities.

New small γ-turn type N-primary amino terminal tripeptide organocatalyst for solvent-free asymmetric aldol reaction of various ketones with aldehydes.

New small γ-turn type N-primary amino terminal tripeptides were synthesized and their functionality as an organocatalyst was examined in the asymmetric aldol reaction of various ketones with different aromatic aldehydes under solvent-free neat conditions to afford the desired chiral anti-aldol products in good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn : anti/13 : 87 dr, up to 99% ee).

Highly enantioselective immobilized prolinamide-catalyzed aldol reactions in continuous-flow systems: effect of water on the catalyst lifetime and application in the synthesis of a chiral fenpentadiol analogue

A highly practical continuous-flow system for aldol reactions of ketones and trifluoroacetophenones has been developed.

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.

Front Cover Picture: Zinc Acetate Catalyzed Enantioselective Reductive Aldol Reaction of Ketones (Adv. Synth. Catal. 7/2020)

Front Cover Picture: Zinc Acetate Catalyzed Enantioselective Reductive Aldol Reaction of Ketones (Adv. Synth. Catal. 7/2020)

Zinc Acetate Catalyzed Enantioselective Reductive Aldol Reaction of Ketones

AbstractA highly enantioselective method for the synthesis of β‐hydroxy esters via reductive aldol reaction of acrylates with aryl and heteroaromatic ketones is described. In situ generated catalyst composed of zinc acetate and chiral diamine afforded enantioenriched tertiary alcohols in high yields and with excellent enantioselectivity (up to 91% ee). This is also the first successful application of the zinc hydride reagent in stereoselective reductive aldol reactions of ketones.magnified image

Evaluation of Zn2+ Coordination Structures in Chiral Zn2+ Complexes Based on Shape Measurement Factors: Relationships between Activity and the Coordination Structure

We previously reported on enantioselective aldol reactions of acetone and cyclic ketones with benzaldehyde derivatives catalyzed by chiral Zn2+ complexes that mimic class II aldolases. The results and mechanistic studies indicated that the catalytic activity of Zn2+ complexes is dependent not only on the coordination numbers of Zn2+ but also on its coordination structure. In this study, we report on shape measures (abbreviated as S values in this manuscript) of such Zn2+ complexes with respect to the 5‐coordination structure based on calculations with continuous shape measures (CShM) using their crystal structures. The S values of Zn2+ ions in Zn2+ complexes for trigonal bipyramidal (D3h) or square pyramidal (C4v) structures suggest that Zn2+ ions in the catalytically active Zn2+ complexes possess D3h and C4v structures, while Zn2+ ions in the unreactive Zn2+ complex has a C4v structure. Moreover, the S values of Zn2+ were calculated with respect to 6‐coordination geometry, based on the assumption that aldol reactions proceed via 6‐membered transition states, and it was implied that 6‐coordinated Zn2+ ions in aldol‐active Zn2+ complexes prefer an octahedron structure (Oh). These results for the S values of Zn2+ ions in the active Zn2+ complexes and those for complexes reported by other research groups suggest that the transition of 5‐coordinated D3h to the 6‐coordinated Oh structure is essential for achieving catalytic stereoselective aldol reactions.

Direct Access to β-Trifluoromethyl-β-hydroxy Thioesters by Biomimetic Organocatalytic Enantioselective Aldol Reaction

A broadly applicable biomimetic enantioselective decarboxylative catalytic aldol reaction of trifluoromethyl ketones with malonic acid half-thioesters (MAHTs) is described. Utilizing cinchona-based thioureas as highly efficient polyketide synthase-mimic catalysts, chiral tertiary aldols, β-trifluoromethyl-β-hydroxy thioesters, were obtained in up to 99% yield and 95% ee. Facile transformation of the thioester moiety of the aldol adducts showcases the synthetic utility of this biomimetic aldol protocol to deliver a range of chiral trifluoromethylated tertiary aldol pharmacophores.

Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols by Vinylogous Aldol Reaction of 3-Methylcyclohex-2-en-1-one with (Het)aryl Trifluoromethyl Ketones

A direct enantioselective vinylogous aldol reaction of trifluoromethyl ketones with 3-methylcyclohex-2-en-1-one through hydrogen-bond-directing dienamine catalysis by a diamine–sulfonamide catalyst has been demonstrated. A range of trifluoromethylated tertiary alcohols were efficiently produced in yields of up to 86% and with 93% enantioselectivity.

Development of C2-Symmetric Chiral Bifunctional Triamines: Synthesis and Application in Asymmetric Organocatalysis.

The synthesis and application of a newly designed C2-symmetric chiral bifunctional triamine family ( C2-CBT) is reported. These enantiopure chiral triamine scaffolds can be accessed in multigram amounts from simple amino acids while avoiding chromatographic purification. As a proof of principle, C2-CBT has been studied in the aldol reaction of cyclic ketones with isatins, with the target tertiary alcohols being formed in a highly efficient manner. Catalyst recovery by simple extraction techniques and subsequent reuse has been performed.

A new type of amino amide organocatalyzed enantioselective crossed aldol reaction of ketones with aromatic aldehydes

A new type of amino amide organocatalysts was designed and synthesized from commercially available amino acids in easy steps. Their catalytic activities were examined in enantioselective crossed aldol reaction of various acyclic and cyclic ketones with aromatic aldehydes to afford the corresponding chiral anti-aldol adducts with good to excellent chemical yields, diastereoselectivities and enantioselectivities (up to 99%, up to syn:anti = 1:99, up to 97% ee).