Enantioselective Henry Reaction Research Articles

Polytopic bis(oxazoline)-based ligands for recoverable catalytic systems applied to the enantioselective Henry reaction.

Several kinds of polytopic chiral ligands (including ditopic, tritopic and tetratopic), based on the bis(oxazoline) and azabis(oxazoline) motifs, have been tested in the preparation of recoverable catalytic systems for the Henry reaction. The results obtained with the different ligands are, in general, good, but they point to the existence of a delicate balance between the coordinating ability of the ligand, the catalytic activity and the recovery of the catalyst by formation of the coordination polymer, related to the easiness to form oligomeric species in solution.

Enantioselective Henry Reaction Catalyzed By Supported Transition Metal Complexes

This present mini-review summarizes the recently published development and trends concerning catalysts based on immobilized complexes of transition metals which are designated for asymmetric Henry reaction. The paper presents examples of originally homogeneous catalysts which were anchored to organic carriers (such as dendrimers, polymers) or inorganic materials. The catalysts based on organic carriers are classified and discussed in accordance to their solubility in reaction medium. In the case of inorganic materials, the discussed catalysts were anchored to different types of surface of micro- and nano-particles. The discussion concerns the effect of immobilization of catalysts on the overall reaction yield, enantioselectivity, possible recycling, and the effect of recycling on the abovementioned parameters.

Copper(II)-containing C2-symmetric bistetracarboline amides in enantioselective Henry reactions

A series of new C2-symmetric chiral diamides were synthesized from l-tryptophan and used as chiral ligands chelated with Cu(II) in enantioselective Henry reactions. Ligand 4a with CuCl2·2H2O (5%) showed effective catalytic efficiency in Henry reaction. High yields (up to 99%) and excellent enantioselectivities (up to 98%) were achieved for both aromatic and aliphatic aldehyde substrates.

Nickel-Catalyzed Enantioselective Henry Reaction

Nickel-Catalyzed Enantioselective Henry Reaction

ChemInform Abstract: Synthesis of Tunable Diamine Ligands with Spiro Indane‐2,2′‐pyrrolidine Backbone and Their Applications in Enantioselective Henry Reaction.

Novel diamine ligands with spiro indane-2,2′-pyrrolidine scaffold were synthesized starting from Seebach’s oxazolidinone 6 and were subsequently employed in asymmetric Henry reaction. Following the initial experimental findings, further synthesis resulted in two types of spiro diamines, with varying substituents at both nitrogen atoms. Ligands of type A, containing a small substituent at N-1′ atom, and a large group at N-1 atom gave predominantly the S-configured β-nitroalcohol, while ligands of type B, with the reversed location of small and large substituents furnished the R-configured product. Both types of ligands turned out to be versatile catalysts for the Henry reaction between nitromethane and an assortment of aryl as well as alkyl aldehydes offering either S- (lig. A) or R-configured (lig. B) nitroalcohols in a good to high chemical yield and an excellent enantioselectivity up to 99% ee.

ChemInform Abstract: syn‐ and Enantioselective Henry Reactions of Aliphatic Aldehydes and Application to the Synthesis of Safingol.

Fundamental Research Funds for the Central Universities [2010121014]; Natural Science Foundation of Fujian Province [2013J10011]

ChemInform Abstract: Recoverable Salen‐Based Macrocyclic Chiral Complexes; Catalysts for Enantioselective Henry Reactions.

Abstract Cobalt and chromium complexes have been prepared from chiral calix–salen cyclic ligands. The corresponding tetrahydrosalen reduced forms have been used for copper salt complexation. These new chiral catalysts have been tested for their ability to promote asymmetric Henry reactions between various aldehydes and nitromethane under heterogeneous conditions. The best results were obtained by using tetrahydrosalen-based copper macrocycles, in terms of activity, selectivity, and stability during the recycling process. Ten consecutive runs could indeed be performed with the same catalyst batch to produce the target 1-(2-methoxy-phenyl)-2-nitro-ethanol with highly stable values in terms of yield and enantioselectivity (up to 94% ee).

ChemInform Abstract: Copper‐Catalyzed Enantioselective Henry Reaction of Enals and Subsequent Iodocyclization: Stereoselective Construction of Chiral Azatricyclic Frameworks.

AbstractThe presented method gives access to a broad scope of functionalized β‐nitro allylic alcohols in high yields and enantioselectivities from cyclic and acyclic enals.

Novel catalysts for the enantioselective Henry reaction

Two novel catalytic systems based on the CuII complexes with N-(3,5-dibromo-2-hydroxybenzyl)- and N-(2-hydroxy-3-nitrobenzyl)-(S)-α,α-diphenylprolinols were developed. These systems catalyze the condensation of 4-nitrobenzaldehyde with nitromethane to produce S-nitroaldol with maximum enantiomeric excess of >90% (99% yield). The reactions of nitromethane with aliphatic aldehydes give the corresponding products in the yields above 80% and ee > 90%.

Synthesis of Tunable Diamine Ligands with Spiro Indane-2,2′-pyrrolidine Backbone and Their Applications in Enantioselective Henry Reaction

Novel diamine ligands with spiro indane-2,2′-pyrrolidine scaffold were synthesized starting from Seebach’s oxazolidinone 6 and were subsequently employed in asymmetric Henry reaction. Following the initial experimental findings, further synthesis resulted in two types of spiro diamines, with varying substituents at both nitrogen atoms. Ligands of type A, containing a small substituent at N-1′ atom, and a large group at N-1 atom gave predominantly the S-configured β-nitroalcohol, while ligands of type B, with the reversed location of small and large substituents furnished the R-configured product. Both types of ligands turned out to be versatile catalysts for the Henry reaction between nitromethane and an assortment of aryl as well as alkyl aldehydes offering either S- (lig. A) or R-configured (lig. B) nitroalcohols in a good to high chemical yield and an excellent enantioselectivity up to 99% ee.

ChemInform Abstract: Novel C2‐Symmetric Bis‐Oxazoline Ligands.

AbstractTwo newly synthesized chiral catalysts are tested in the enantioselective Henry reaction of aldehyde (I) with nitromethane (II) to give the corresponding alcohol albeit with poor enantioselectivity.

Syn‐ and Enantioselective Henry Reactions of Aliphatic Aldehydes and Application to the Synthesis of Safingol

Atom-economic synthesis: The syn- and highly enantioselective Henry reactions of aliphatic aldehydes catalyzed by a readily available β-amino alcohol copper catalyst were developed and successfully utilized in the synthesis of safingol. The ligand could be easily recovered without any racemization (see scheme).

Recoverable salen-based macrocyclic chiral complexes; catalysts for enantioselective Henry reactions

Cobalt and chromium complexes have been prepared from chiral calix–salen cyclic ligands. The corresponding tetrahydrosalen reduced forms have been used for copper salt complexation. These new chiral catalysts have been tested for their ability to promote asymmetric Henry reactions between various aldehydes and nitromethane under heterogeneous conditions. The best results were obtained by using tetrahydrosalen-based copper macrocycles, in terms of activity, selectivity, and stability during the recycling process. Ten consecutive runs could indeed be performed with the same catalyst batch to produce the target 1-(2-methoxy-phenyl)-2-nitro-ethanol with highly stable values in terms of yield and enantioselectivity (up to 94% ee).

Organic Solvent Nanofiltration as a Tool for Separation of Quinine-Based Organocatalysts

Organic solvent nanofiltration (OSN) promises to be a versatile tool for mild and energy-saving downstream processing. In this case study, the use of modern solvent-resistant membranes to separate organocatalysts from reaction media was investigated. Commercially available membranes with molecular weight cut-offs (MWCOs) between 150 and 500 g mol–1 were used. They showed high rejections of up to 99% for native catalysts in THF. The enantioselective Henry reaction of ethyl pyruvate and nitromethane catalyzed by benzoyl cupreine was used to demonstrate the potential of this technique for preparative use.

Copper‐Catalyzed Enantioselective Henry Reaction of Enals and Subsequent Iodocyclization: Stereoselective Construction of Chiral Azatricyclic Frameworks

Copper‐Catalyzed Enantioselective Henry Reaction of Enals and Subsequent Iodocyclization: Stereoselective Construction of Chiral Azatricyclic Frameworks

Copper‐Catalyzed Enantioselective Henry Reaction of Enals and Subsequent Iodocyclization: Stereoselective Construction of Chiral Azatricyclic Frameworks

In the frame: A cascade sequence combining an asymmetric Henry reaction and a stereoselective intramolecular iodocyclization provides direct access to an enantioenriched tricyclic hexahydrochromeno[4,3-b]pyrrole framework (see scheme). The Henry reaction is catalyzed by copper in the presence of L1.

Synthesis of C 1-symmetric primary-secondary diamines and their application in the enantioselective Henry reaction

Two new C1-symmetric primary-secondary diamines were synthesized via the reaction of (S,S)-1,2-diphenyl ethylene diamine with 3,5-ditert-butyl salicylaldehyde and salicylaldehyde, respectively, followed by reduction with NaBH4. The combination of the ligand from 3,5-ditert-butyl salicylaldehyde with CuBr could effciently catalyze the Henry reaction to afford β-nitroalkanols in moderate to good yields (up to 87%) and high enantioselectivities (up to 88% ee). A possible mechanism of the reaction was proposed.

ChemInform Abstract: Planar Chiral [2.2]Paracyclophane‐Based Bis(thiourea) Catalyst: Application to Asymmetric Henry Reaction.

AbstractA planar chiral bis(thiourea) catalyst is designed and synthesized, which allows for highly enantioselective Henry reactions.

Enantioselective Henry Reaction Catalyzed by “Ship in a Bottle” Complexes

Two chiral Schiff-base complexes of copper(II) have been successfully encapsulated inside the cavity of zeolite-NaY via a "ship in a bottle" synthesis method. The presence of the two complexes inside the cages of zeolite-Y has been confirmed based on various spectrochemical and physicochemical techniques, viz. FTIR, UV-vis/DRS, ESR, XPS, CV, EDX, SEM, and TGA. Zeolite-encapsulated chiral copper(II) Schiff-base complexes are found to give a high-enantioselective (84% ee, R conformation) nitro-aldol product at -20 °C. The encapsulated copper complexes are found to show higher catalytic efficiency than their homogeneous counterparts under identical conditions. Density functional theory (DFT) calculation has been implemented to understand the effect of the zeolite matrix on structural, electronic, and reactivity properties of the synthesized complexes. Theoretical calculation predicts that upon encapsulation into the zeolite matrix the Cu center becomes more susceptible to nucleophilic attack, favoring a nitro-aldol reaction. A plausible mechanism is suggested based on the experimental and theoretical results. The structures of reaction intermediates and transition state(s) involved in the catalytic cycle are derived using DFT.

Synthesis and application of new iminopyridine ligands to enantioselective copper(II)-catalyzed Henry reaction

Chiral iminopyridines obtained by reaction between a variety of chiral amines and pyridyl aldehydes or ketones were assessed as catalysts in the enantioselective Henry reaction between nitromethane and 2-methoxybenzaldehyde in the presence of copper(II) acetate. 1-(2-Methoxyphenyl)-2-nitroethanol was obtained in moderate yields and good enantioselectivities (up to 82% ee) under straightforward experimental conditions without the need for air or moisture exclusion. The best enantioselectivity (82% ee) was obtained by an iminopyridine based on a camphane skeleton.