Organocatalytic Asymmetric Aldol Research Articles

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates.

A practical enantioselective N-selective nitroso aldol reaction of α-methylmalonamates with a nitrosoarene is reported. The reaction employs the Takemoto thiourea catalyst for the induction of enantioselectivity, and the corresponding optically active oxyaminated malonamates were obtained in reasonably good yields.

Three-Pot Synthesis of Chiral Anti-1,3-diols through Asymmetric Organocatalytic Aldol and Wittig Reactions Followed by Epoxidation and Reductive Opening of the Epoxide.

A three-pot asymmetric synthesis of the anti-1,3-diol unit was developed. In the first pot, enantioselective aldol reaction of aldehydes proceeds, catalyzed by organocatalyst, followed by either Wittig or Horner-Wadsworth-Emmons reactions to afford δ-hydroxy α,β-unsaturated carbonyls with excellent enantioselectivity. Diastereoselective hydroxy-directed anti-epoxidation proceeds in the next pot by the use of tert-BuOOH and LiHMDS. Reductive opening of the epoxide proceeds in a third pot to afford anti-β,δ-hydroxy carbonyl compounds with excellent diastereo- and enantioselectivity.

An Asymmetric Organocatalytic Aldol Reaction of a Hydrophobic Aldehyde in Aqueous Medium Running in Flow Mode

Reaction conditions have been identified to conduct a one-pot asymmetric organocatalytic aldol reaction with a hydrophobic substrate in aqueous medium via a process running in flow mode. By employing a mixture of water and 2-propanol, a hydrophobic aldehyde and 3.6 mol% of an organocatalyst, this microreactor process affords the desired aldol adduct with a conversion of 74% and an enantioselectivity of 89% after a reaction time of 60 minutes.

Two-Pot Synthesis of Chiral 1,3-syn-Diols through Asymmetric Organocatalytic Aldol and Wittig Reactions Followed by Domino Hemiacetal/Oxy-Michael Reactions.

A two-pot synthetic method to construct the chiral syn-1,3-diol unit has been developed from three aldehydes and either Wittig or Horner-Wadsworth-Emmons reagents. In the first pot, chiral δ-hydroxy α,β-unsaturated ketones are synthesized with excellent enantioselectivity by the organocatalyst-mediated asymmetric direct aldol reaction of two different aldehydes, followed by either Wittig or Horner-Wadsworth-Emmons reactions. In the second pot, domino acetalization with an aldehyde and subsequent oxy-Michael reaction proceeds in the presence of NaClO4 and a catalytic amount of Bi(OTf)3 (OTf=trifluoromethanesulfonate) to provide the chiral 1,3-syn-diol derivative with excellent diastereoselectivity. Diospongin C and yashabushidiol A have been synthesized efficiently by using the present method as a key step.

First Tandem‐Type One‐Pot Process Combining Asymmetric Organo‐ and Biocatalytic Reactions in Aqueous Media Exemplified for the Enantioselective and Diastereoselective Synthesis of 1,3‐Diols

A suitable “process window” was identified for the combination of an asymmetric organocatalytic aldol reaction and subsequent biocatalytic reduction in aqueous medium, which thus enabled the enantio‐ and diastereoselective synthesis of 1,3‐diols in a tandem‐type, one‐pot process. A key feature of this one‐pot synthesis is the high 500 mm loading of the aldehyde substrate used as a starting material.

Synthesis of D-pantolactone via Combined a Novel Organocatalyst Catalyzed Asymmetric Aldol Reaction and Hydrogenation Catalyzed by Cu-/SiO<sub>2</sub>

The combination of an asymmetric organocatalytic aldol reaction with a subsequent hydrogenation for the synthesis of D-pantolactone is demonstrated. This process consists of an initial aldol reaction catalyzed by a novel chiral L- histidine-modified-ionic-liquid- [EMIm] [His], which has been designed and synthesized as an efficient recoverable catalyst for the asymmetric aldol reaction with superior enantioselectivity in CH₂Cl₂, than L-histidine itself. [EMIm] [His] retains its activity and enantioselectivity over at least five reaction cycles, and its universal applicability has been demonstrated. Moreover optimum process of Cu-/SiO₂-catalysed hydrogenation of condensation product- (D) -3- formyl -2- hydroxy -3- ethyl butyrate to obtain D-pantolactone has been established allowing the synthesis of D-pantolactone in >99% purity, 93% yield and 93% enantiomeric excesse (ee). The results show that CuO-CeO₂/SiO₂ exhibits better catalytic activity than CuO/SiO₂ for better dispersion and larger surface area, and the best reaction conditions are as follows: 120°C, <i>n</i> (H₂): <i>n</i> (isobutylaldehyde) =80:1, P (H₂) =8.0 MPa, liquid airspeed: 0.6 h^-1.

Chemoenzymatic synthesis of vitamin B5-intermediate (R)-pantolactone via combined asymmetric organo- and biocatalysis.

The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a "one-pot-like" process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%.

ChemInform Abstract: Binaphthyl Based Molecules for Asymmetric Organocatalytic Aldol Reactions: Recent Developments from a Successful Record

AbstractReview: 82 refs.

Binaphthyl Based Molecules for Asymmetric Organocatalytic Aldol Reactions: Recent Developments from a Successful Record

The careful selection of a suitable chiral backbone is vital for the preparation of any modern ligand for asymmetric catalysis, where binaphthyl based ligands are considered paradigmatic and systematically used in a diversity of asymmetric catalysed reactions, with emphasis for organocatalysis. Due to the vastness of possible organocatalytic applications, this review article is mainly focused on the asymmetric aldol and vinylogous aldol reactions organocatalysed by binaphthyl-based molecules. Special attention is given to catalytic results, particularly on enantio- and diastereoselectivity obtained by the use of the above binaphthyl chiral inductors. Keywords: Aldol, binaphthyl derivatives, organocatalysis, C-C bond, Asymmetric catalysis, BINOL, BINAM, NOBIN.

ChemInform Abstract: Asymmetric Organocatalytic Aldol Reaction in Water: Mechanistic Insights and Development of a Semi‐Continuously Operating Process.

AbstractA detailed study on the influence of the catalyst loading on conversion and enantioselectivity of the aldol reaction between acetone and an aromatic aldehyde is presented.

Asymmetric Organocatalytic Aldol Reaction in Water: Mechanistic Insights and Development of a Semi-Continuously Operating Process

A detailed study on the impact of the catalyst loading on conversion and enantioselectivity of the direct aldol reaction of an aldehyde and acetone in aqueous solvent with nonimmobilized and immobilized proline amide-based organocatalysts is described. Based on a polymer-supported catalyst, batch and semi-continuously operating processes, comprising recycling studies in the latter case, were investigated.

A Liquid–Liquid Biphasic Homogeneous Organocatalytic Aldol Protocol Based on the Use of a Silica Gel Bound Multilayered Ionic Liquid Phase

AbstractAn innovative two stage liquid–liquid biphasic homogeneous protocol for the asymmetric organocatalytic aldol reaction is proposed, based on the use of the cis‐ion‐tagged proline 8 dissolved in the liquid film of a multilayered ionic liquid covalently bonded to silica gel 4. The resulting catalytically active material 9 is first soaked with cyclohexanone in the presence of water, resulting in a semi‐transparent gel, then the aldehyde is added and the mixture stirred at RT. In the first stage, 4 acts as a catalyst reservoir that delivers 8 to the cyclohexanone phase allowing the reaction to take place homogeneously. In the second stage, cyclohexanone is removed under vacuum and the resulting slurry is extracted with anhydrous diethylether. Now 4 acts as a catalyst sponge, redissolving 8. Product extraction is extremely selective; no trace of catalyst is detected in the product‐containing phase, and 9 can be easily reused several times with high cumulative productivity values (up to 523).

A Highly Efficient Asymmetric Organocatalytic Aldol Reaction in a Ball Mill.

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.

Bimorpholines as Alternative Organocatalysts in Asymmetric Aldol Reactions

Asymmetric organocatalytic aldol condensation is discussed on the basis of intramolecular and inter-molecular reactions. In addition to the widely used proline and its derivatives an application of the new type of the organocatalyst – bimorpholines in the above-mentioned reactions is described. The new catalyst has a unique C2-symmetric skeleton with four acceptor sites that makes it stereoselective and efficient. Small changes in the structure of the catalyst lead to a remarkable loss of selectivity.

A Highly Efficient Asymmetric Organocatalytic Aldol Reaction in a Ball Mill

Anti-aldol products with up to >99 % enantiomeric excess (ee) have been obtained by proline catalysis in excellent yields under experimentally simple solvent-free conditions. Efficient mixing of all the components is accomplished by applying a mechanochemical technique (ball milling). The catalysis is air and moisture tolerant and can be performed with non-purified starting materials. Even mixtures of solely solid compounds react, giving (mostly solid) products through a partially homogeneous (honey-like) intermediate melt. Since the reactant ratio is almost 1:1 (avoiding the common excess of ketone), the product isolation is easy leading to high aldol product yields.