Michael Addition Reactions Of Aldehydes Research Articles

Organocatalytic asymmetric Michael addition reaction of aldehydes with 2-furanones: experimental, applications and DFT studies

Organocatalytic asymmetric Michael additions of aldehydes to 2-furanones are successfully conducted and have been applied to the synthesis of vorapaxar's analogues.

Cover Feature: α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides (Eur. J. Org. Chem. 37/2021)

The Cover Feature shows the merging of chiral organic catalysts with inorganic materials, which gives rise to an hybrid organic–inorganic catalytic system able to catalyze the Michael addition of α,α-disubstituted aldehydes to maleimides under solvent free reaction conditions. The recovery, reusability and environmentally friendly conditions are represented by the illustrated landscape. More information can be found in the Full Paper by J. M. Landeros, E. Juaristi et al.

α‐Amino Acids and α,β‐Dipeptides Intercalated into Hydrotalcite: Efficient Catalysts in the Asymmetric Michael Addition Reaction of Aldehydes to N‐Substituted Maleimides

AbstractIn this work, a series of α‐amino acids (L‐Phe, D‐Phe, L‐Trp) and several α,β‐dipeptides (H2N‐L‐Val‐N‐Bn‐β‐Ala‐COOH and H2N‐L‐Leu‐N‐Bn‐β‐Ala‐COOH) intercalated into hydrotalcite (Mg/Al, x=0.333) were prepared by high speed ball milling (HSBM) assisted rehydration/reconstruction methods, followed by sonication and mechanical stirring. All organic‐inorganic hybrid samples were characterized by powder X‐ray diffraction (XRD) and FTIR‐ATR spectroscopy. The catalytic activity of the resulting hydrotalcite‐supported materials (natural and hybrid) was evaluated in the asymmetric Michael addition reaction of α,α‐disubstituted‐aldehydes to N‐substituted‐maleimides. Pristine (HTS), calcined (HTC) and water‐reconstructed (HTR‐l) hydrotalcite‐derived materials exhibited very low catalytic activities, affording racemic mixtures of the anticipated Michael adduct. By contrast, hybrid materials showed better activities, especially HTR‐α‐amino acid catalysts afforded Michael products in up to 94 % yield and with rather high enantioselectivity (enantiomeric ratio (e.r.) up to 99 : 1) at room temperature under neat reaction conditions. The effect of solvents and Brønsted basic or acidic additives was evaluated using the best hybrid catalyst, HTR‐L‐Phe. In addition, recycling and reuse of the catalyst (up to 4 cycles) and large‐scale experiments was successfully carried out.

Synthesis of polymer microsphere‐supported chiral pyrrolidine catalysts by precipitation polymerization and their application to asymmetric Michael addition reactions

AbstractPolymer microsphere‐supported chiral pyrrolidine catalysts were successfully synthesized by a precipitation polymerization incorporating a methacrylate monomer bearing chiral N‐Boc‐pyrrolidine moiety, followed by removal of the N‐Boc groups. The resulting polymeric catalysts were applied to the asymmetric Michael addition reactions of aldehydes with alkyl vinyl ketones. The effects of the comonomer, the molar ratios within the catalyst, the catalyst loading, the temperature, and the solvent on the catalytic performance were investigated in detail. The reactions were found to proceed smoothly in the absence of a solvent. A hydrophobic polystyrene‐based chiral pyrrolidine catalyst exhibited high reactivity (up to 97% yield) and enantioselectivity (up to 95% ee) during these reactions. The catalyst could also be recovered and reused up to five times without significant loss of activity.

Asymmetric Michael addition reactions of aldehydes to β-nitrostyrenes catalyzed by (S)–N-(D-prolyl-L-prolyl)-1 -triflicamido-3 -phenylpropan-2-amine

In an attempt to improve the catalytic ability of ( S )– N -(D-prolyl)-1-triflicamido-3-phenylpropan-2-amine, a catalyst previously reported by us for the asymmetric Michael addition of aldehydes to β-nitrostyrenes, 4 new molecules were designed and synthesized by increasing the distance between the triflicamide group and the secondary amino group in the catalyst. Under the optimized reaction conditions ( S )– N -(D-prolyl-L-prolyl)-1-triflicamido-3-phenylpropan-2-amine exhibited high and improved catalytic activity and stereoselectivity at a lower catalyst loading (3 mol%). In the studies done with a large number of aldehydes and β-nitrostyrenes, the Michael adducts were obtained in high yields (up to 94%) and with excellent enantioselectivities (up to 98% ee) and with good to excellent diastereoselectivities (up to 98:2 dr).

Enantioselective Michael Addition of Aldehydes to β‐Nitrostyrenes Catalyzed by (S)‐N‐(D‐Prolyl)‐1‐triflicamido‐3‐phenylpropan‐2‐amine

A new organocatalyst for the asymmetric Michael addition reaction of aldehydes with β‐nitrostyrenes is developed by coupling D‐proline with (S)‐1‐triflicamido‐3‐phenylpropan‐2‐amine, which in turn is prepared from L‐phenylalaninol. The Michael addition products were obtained in very high yields (up to 93 %) and with excellent enantioselectivity (up to 97 % ee) and high diastereoselectivity (up to >99:1 dr). The catalyst is effective for reactions between α‐branched aldehydes and β‐nitrostyrenes.

D-Prolyl-2-(trifluoromethylsulfonamidopropyl)pyrrolidine: An Organocatalyst for Asymmetric Michael Addition of Aldehydes to β-Nitroalkenes at Ambient Conditions.

Four 2-(trifluoromethylsulfonamidoalkyl)pyrrolidines and their d-prolinamides were prepared and screened as organocatalysts for the Michael addition reaction of aldehydes with β-nitroalkenes at rt and without the use of additives. d-Prolyl-2-(trifluoromethylsulfonamidopropyl)pyrrolidine was found to be the best among the molecules studied, which yielded γ-nitro aldehydes in very high yields (up to 95%), with high diastereoselectivity (up to >99:1) and with up to 97% ee.

Polarity‐Reversed Allylations of Aldehydes, Ketones, and Imines Enabled by Hantzsch Ester in Photoredox Catalysis

AbstractThe polarity reversal (umpolung) reaction is an invaluable tool for reversing the chemical reactivity of carbonyl and iminyl groups, which subsequent cross‐coupling reactions to form C−C bonds offers a unique perspective in synthetic planning and implementation. Reported herein is the first visible‐light‐induced polarity‐reversed allylation and intermolecular Michael addition reaction of aldehydes, ketones, and imines. This chemoselective reaction has broad substrate scope and the engagement of alkyl imines is reported for the first time. The mechanistic investigations indicate the formation of ketyl (or α‐aminoalkyl) radicals from single‐electron reduction, where the Hantzsch ester is crucial as the electron/proton donor and the activator.

Polarity-Reversed Allylations of Aldehydes, Ketones, and Imines Enabled by Hantzsch Ester in Photoredox Catalysis.

The polarity reversal (umpolung) reaction is an invaluable tool for reversing the chemical reactivity of carbonyl and iminyl groups, which subsequent cross-coupling reactions to form C-C bonds offers a unique perspective in synthetic planning and implementation. Reported herein is the first visible-light-induced polarity-reversed allylation and intermolecular Michael addition reaction of aldehydes, ketones, and imines. This chemoselective reaction has broad substrate scope and the engagement of alkyl imines is reported for the first time. The mechanistic investigations indicate the formation of ketyl (or α-aminoalkyl) radicals from single-electron reduction, where the Hantzsch ester is crucial as the electron/proton donor and the activator.

ChemInform Abstract: Epiandrosterone‐Derived Prolinamide as an Efficient Asymmetric Catalyst for Michael Addition Reactions of Aldehydes to Nitroalkenes.

AbstractThe title novel catalyst can be easily prepared from commercially available Boc‐L‐Proline and epiandrosterone.

POSS supported diarylprolinol silyl ether as an efficient and recyclable organocatalyst for asymmetric Michael addition reactions

The POSS supported (S)-α,α-diphenylprolinol trimethylsilyl ether catalyst was synthesized and applied in the asymmetric Michael addition reactions of aldehydes and arylnitroalkenes, providing the products in good yields with excellent enantioselectivities and good diastereoselectivities. The POSS supported catalyst can be readily recycled and reused for further transformations at least eight cycles without observing significant decrease in yield and stereoselectivity.

Epiandrosterone-derived prolinamide as an efficient asymmetric catalyst for Michael addition reactions of aldehydes to nitroalkenes

Epiandrosterone derivatives-organocatalyzed asymmetric Michael addition of aldehydes to nitroalkenes was investigated. Among the various catalysts, a novel type of epiandrosterone-derived L-prolineamide catalyst was synthesized and exhibited better performance in both catalytic activity and stereoselectivity, providing the products with high yields (up to 98%), excellent enantioselectivities (up to 99% ee) and diastereoselectivities (up to 99 : 1 dr), and low catalyst loading (5 mol%).

ChemInform Abstract: Structure—Reactivity Studies of Simple 4‐Hydroxyprolinamide Organocatalysts in the Asymmetric Michael Addition Reaction of Aldehydes to Nitroolefins.

AbstractFrom a series of 15 4‐hydroxyprolinamides compounds (I) show promising activity as catalysts in the title reaction.

ChemInform Abstract: Highly Efficient Asymmetric Michael Addition of Aldehyde to Nitroolefin Using Perhydroindolic Acid as a Chiral Organocatalyst.

AbstractPerhydroindolic acid, obtained as a by‐product in the industrial production of a trandolapril intermediate, is used as a chiral organocatalyst in asymmetric Michael addition reactions of aldehydes to nitroolefins.

Structure‐Reactivity Studies of Simple 4‐Hydroxyprolinamide Organocatalysts in the Asymmetric Michael Addition Reaction of Aldehydes to Nitroolefins

AbstractA series of simple 4‐hydroxyprolinamides was synthesised and they were found to act as organocatalysts for the asymmetric conjugate addition of aldehydes to nitroolefins in excellent yields (98%), with complete diastereoselectivity (99:1, syn:anti) and enantioselectivity (98% ee for syn). Furthermore, the use of low catalyst loadings (5 mol%) and a low aldehyde molar excess (1.5 equivalents) were achieved.

Chiral pyrrolidine quaternary derivatives as organocatalysts for asymmetric Michael additions

A series of chiral pyrrolidine quaternary derivatives were designed and synthesized. It was found that these derivatives are highly efficient organocatalysts for the asymmetric Michael addition reactions of aldehydes and ketones to nitroolefins with high yields (up to 96%), high enantioselectivities (up to 99% ee), and high diastereoselectivities (up to 97:3 dr). Furthermore, catalyst 7a could be recycled without remarkable loss of catalytic activity and stereoselectivity.

Highly efficient asymmetric Michael addition of aldehyde to nitroolefin using perhydroindolic acid as a chiral organocatalyst

Perhydroindolic acids, the by-products obtained in the industrial production of a trandolapril intermediate, were used as chiral organocatalysts in asymmetric Michael addition reactions of aldehydes to nitroolefins. These proline-like catalysts are unique for their rigid bicyclic structure with two H atoms attached to the bridgehead C atoms lying on the opposite side of the ring. They therefore showed high efficiency in asymmetric Michael additions of aldehydes to nitroolefins. Under the optimal conditions, excellent diastereo- and enantioselectivities (up to 99/1 dr and 98% ee) were obtained with high chemical yields for a series of aldehydes and nitroolefins using only 5 mol% catalyst loading. The methodology features easily available catalysts, high catalytic efficiency and environmentally green procedures.

ChemInform Abstract: Ionic Liquid‐Supported (ILS) (S)‐Pyrrolidine Sulfonamide for Asymmetric Michael Addition Reactions of Aldehydes with Nitroolefins.

AbstractA novel ionic liquid supported organocatalyst (ILOC) is developed, which efficiently catalyzed asymmetric Michael addition reactions of aldehydes to nitroolefins using only two equivalents of the aldehyde.

Ionic Liquid-Supported (ILS) (S)-Pyrrolidine Sulfonamide for Asymmetric Michael Addition Reactions of Aldehydes with Nitroolefins

A class of ionic liquid supported (ILS) (S)-pyrrolidine sulfonamide organocatalyst (1c), which was developed earlier in our lab, has been applied to a wider range of Michael addition reaction, involving various aryl-substituted nitroolefins and a series of aldehydes. Catalyst 1c catalyzes Michael additions in which only 2 equivalents of aldehydes to each equivalent of nitroolefin are required. With 10 mol% of ILS catalyst 1c loading, moderate to excellent yields (51- 98%) with moderate enantioselectivities (28-83% ee) and high diastereoselectivities (syn/anti ratio up to 97/3) were obtained. Moreover, the catalyst 1c could be easily recycled and reused for at least 5 times with slightly reduced activities. Keywords: Aldehydes, asymmetric catalysis, ionic liquid, michael addition, nitroolefins, cornerstone, enantioselective, organocatalytic, methyl

Enantioselective Organocatalytic Michael Addition of Aldehydes to Trifluoroethylidene Malonates

An efficient, highly enantioselective, organocatalytic Michael addition reaction of aldehydes with trifluoroethylidene malonates is described. The asymmetric reaction provided highly optically pure β-trifluoromethyl aldehydes which can be conveniently transformed into 4,4,4-trifluoromethyl butyric acid and trifluoromethyl substituted δ-lactones without loss in enantioselectivity.