Michael Addition Of Cyclic Ketones Research Articles

Frontispiece: Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

Frontispiece: Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

Frontispiz: Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

Frontispiz: Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis.

Consistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new-to-nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ-nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97 % e.e., >20 : 1 d.r.) and good yield (up to 86 %). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization, and highlights the usefulness of artificial enzymes for extending biocatalysis to further non-natural reactions.

Design and Evolution of an Enzyme for the Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins by Enamine Catalysis

AbstractConsistent introduction of novel enzymes is required for developing efficient biocatalysts for challenging biotransformations. Absorbing catalytic modes from organocatalysis may be fruitful for designing new‐to‐nature enzymes with novel functions. Herein we report a newly designed artificial enzyme harboring a catalytic pyrrolidine residue that catalyzes the asymmetric Michael addition of cyclic ketones to nitroolefins through enamine activation with high efficiency. Diverse chiral γ‐nitro cyclic ketones with two stereocenters were efficiently prepared with excellent stereoselectivity (up to 97 % e.e., >20 : 1 d.r.) and good yield (up to 86 %). This work provides an efficient biocatalytic strategy for cyclic ketone functionalization, and highlights the usefulness of artificial enzymes for extending biocatalysis to further non‐natural reactions.

L-Prolinal Dithioacetal: A Highly Effective Organocatalyst for the Direct Nitro-Michael Addition to Selected Cyclic and Aromatic Ketones

The synthesis of novel l-prolinal dithioacetal and its application as an organocatalyst for the direct Michael addition of cyclic ketones and acetophenone derivatives to trans-β-nitrostyrene and related compounds is described. The prolinal dithioacetal acts as effective catalyst in the case of cyclic ketones of different ring size, in particular five- and six-membered examples, as well as larger and smaller ring systems. High enantioselectivity and diastereoselectivity is observed for different substrates and trans-β-nitrostyrenes. Also, the first asymmetric syntheses of selected 2-methyl-4-nitro-1,3-diphenylbutan-1-one derivatives by application of the obtained organocatalyst is presented.

Studies on the Organocatalytic Enantioselective Michael Addition of Cyclic Ketones and α,α-Disubstituted Aldehydes to α-Nitrostyrenes

Studies on the Organocatalytic Enantioselective Michael Addition of Cyclic Ketones and α,α-Disubstituted Aldehydes to α-Nitrostyrenes

Rhodium(iii)/amine synergistically catalyzed enantioselective Michael addition of cyclic ketones with α,β-unsaturated 2-acyl imidazoles

An enantioselective Michael addition of α,β-unsaturated 2-acyl imidazoles with cyclic ketones catalyzed synergistically by a chiral-at-metal Rh(iii) complex and a secondary amine has been developed, affording the corresponding adducts with up to 98% yield and 99% ee.

ChemInform Abstract: High Pressure Organic Chemistry. Part 40. Enantioselective Synthesis of Quaternary Carbon Stereogenic Centers Through the Primary Amine‐Catalyzed Michael Addition Reaction of α‐Substituted Cyclic Ketones at High Pressure.

AbstractCompounds bearing a quaternary carbon stereogenic center at the α‐position of cyclic ketones are obtained by an efficient new method involving the enantioselective Michael addition of cyclic ketones with acrylates using simple chiral 1‐phenylethylamine as catalyst under high pressure.

ChemInform Abstract: Construction of Chiral 2‐Substituted Octahydroindoles from Cyclic Ketones and Nitroolefins Bearing only One α‐Substituent.

AbstractA dual catalytic system is developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitro olefins bearing only one α‐substituent.

Construction of Chiral 2‐Substituted Octahydroindoles from Cyclic Ketones and Nitroolefins Bearing only One α‐Substituent

AbstractA dual catalytic system has been developed following the screening of a series of chiral primary amine catalysts and chiral phosphoric acid catalysts for the Michael addition of cyclic ketones to nitroolefins bearing only one α‐substituent. The resulting γ‐nitro ketones, which contain a substituent on the carbon connected to the nitro group, were formed in excellent yields (>80%) with high levels of stereoselectivity (up to 94:6 dr and 98% ee) when the reaction was performed in benzene at 0 °C with 10 mol% of the optimal amine/phosphoric acid combination (1:1) as a catalyst. Subsequent reduction of the nitro group followed by intramolecular reductive amination could afford optically active cis‐octahydroindole analogues bearing a non‐functional substituent at their 2‐position.magnified image

ChemInform Abstract: Enantioselective Michael Addition of Cyclic Ketones to Nitroolefins Catalyzed by a Novel Fluorine‐Insertion Organocatalyst.

AbstractA novel fluorinated pyrrolidine is synthesized starting from 4‐hydroxy‐L‐proline.

Enantioselective Michael addition of cyclic ketones to nitroolefins catalyzed by a novel fluorine-insertion organocatalyst

A novel fluorine-insertion organocatalyst, which was designed based on the fluorine–ammonium ion gauche effect, was synthesized and used successfully to catalyze the asymmetric Michael addition of cyclic ketones to nitroolefins. High yields and excellent diastereo- and enantioselectivities were achieved under mild conditions. A possible stereochemical model is also proposed.

ChemInform Abstract: Pyrrolidine‐thioxotetrahydropyrimidinone as an Efficient Organocatalyst for the Enantioselective Michael Addition of Cyclic Ketones to Nitrodienes.

AbstractExcellent diastereoselectivities (crude mixtures) and enantioselectivities are achieved when cyclohexanone is used as the substrate.

ChemInform Abstract: Pyrrolidine Based Chiral Organocatalyst for Efficient Asymmetric Michael Addition of Cyclic Ketones to β‐Nitrostyrenes.

An efficient asymmetric Michael addition of cyclic ketones to β-nitrostyrenes using secondary diamine as an organocatalyst derived from l-proline and (R)-α-methylbenzyl amine has been described. This pyrrolidine based catalyst 1 was found to be very effective to synthesize various γ-nitrocarbonyl compounds in good yield (up to 81%) with excellent stereoselectivity (up to >99:1 dr and >99% ee).

ChemInform Abstract: Highly Enantioselective Michael Addition of Cyclic Ketones to Chalcones Catalyzed by Pyrrolidine‐Based Imides.

AbstractModerate to excellent stereoselectivities are obtained for the title reaction in the presence of a L‐proline derived imide as catalyst (NIM).

Pyrrolidine-thioxotetrahydropyrimidinone as an efficient organocatalyst for the enantioselective Michael addition of cyclic ketones to nitrodienes

Among the various Michael additions, the enantioselective reaction between cyclic ketones and nitrodienes has received little attention in comparison to the corresponding reaction with nitroolefins. A bifunctional organocatalyst consisting of the pyrrolidine moiety and a thioxotetrahydropyrimidinone ring successfully catalyzed this asymmetric transformation. The products of the reaction between various ketones and nitrodienes were obtained in high yields (up to 96%) with excellent diastereo- (up to >98:2 dr) and enantioselectivities (up to 99:1% er).

ChemInform Abstract: Novel Bifunctional Organocatalyst Using Sulfamide as Hydrogen Bonding Donor: Application in Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins.

AbstractThe PSAP organocatalyst is prepared from Boc‐protected L‐proline in 2 steps.

Highly enantioselective Michael addition of cyclic ketones to chalcones catalyzed by pyrrolidine-based imides

An efficient procedure for asymmetric Michael addition reaction of cyclic ketones with low activated chalcones catalyzed by pyrrolidine-based phthalimide and 1,8-Naphthalimide catalysts was developed. The corresponding products were obtained in high yields with high diastereoselectivities (up to 99:1 dr) and high enantioselectivities (up to 96% ee) under mild conditions.

Pyrrolidine based chiral organocatalyst for efficient asymmetric Michael addition of cyclic ketones to β-nitrostyrenes

An efficient asymmetric Michael addition of cyclic ketones to β-nitrostyrenes using secondary diamine as an organocatalyst derived from l-proline and (R)-α-methylbenzyl amine has been described. This pyrrolidine based catalyst 1 was found to be very effective to synthesize various γ-nitrocarbonyl compounds in good yield (up to 81%) with excellent stereoselectivity (up to >99:1 dr and >99% ee).

Novel Bifunctional Organocatalyst Using Sulfamide as Hydrogen Bonding Donor: Application in Asymmetric Michael Addition of Cyclic Ketones to Nitroolefins

A chiral bifunctional organocatalyst using sulfamide as novel type of hydrogen bonding donor has been developed. This catalyst was found to efficiently catalyze the Michael addition of cyclic ketones to nitroolefins in water, and the products were obtained in good yield (up to 97%), and excellent diastereoselectivities (up to >50:1) and enantioselectivities (up to 96%).