Direct Asymmetric Michael Addition Research Articles

Enzyme-Promoted Direct Asymmetric Michael Reaction by Using Protease from Streptomyces griseus

The direct asymmetric Michael addition of malonates and enones was promoted by protease from Streptomyces griseus for the first time. Yields of up to 84% with enantioselectivities of up to 98% enantiomeric excess (ee) were achieved under optimized conditions. Protease from Streptomyces griseus (SGP) was used for the first time as a biocatalyst in asymmetric Michael reaction of malonates.

An amphiphilic organic catalyst for the direct asymmetric Michael addition of cycloketone to nitroolefins in water

A series of amphiphilic proline-derived mercapto imidazole organic catalysts were synthesized and shown to be very effective with an acid cocatalyst for the asymmetric Michael addition reaction of ketones to nitroolefins with high diastereoselectivity (up to 99:1) and execellent enantioselectivity (up to 96%) using water as solvent.

ChemInform Abstract: Direct Asymmetric Michael Addition of Ketones to Chalcones Catalyzed by a Hydroxyphthalimide Derived Triazole—Pyrrolidine.

Abstract An efficient protocol for the enantioselective Michael additions of ketones to chalcones catalyzed by a hydroxyphthalimide linked triazole–pyrrolidine derivative has been developed. The corresponding products, 1,5-dicarbonyl compounds, were obtained in good yields with high levels of stereoselectivities under mild reaction conditions employing benzoic acid as an additive.

Direct asymmetric Michael addition of ketones to chalcones catalyzed by a hydroxyphthalimide derived triazole–pyrrolidine

An efficient protocol for the enantioselective Michael additions of ketones to chalcones catalyzed by a hydroxyphthalimide linked triazole–pyrrolidine derivative has been developed. The corresponding products, 1,5-dicarbonyl compounds, were obtained in good yields with high levels of stereoselectivities under mild reaction conditions employing benzoic acid as an additive.

Multicomponent Combinatorial Development and Conformational Analysis of Prolyl Peptide–Peptoid Hybrid Catalysts: Application in the Direct Asymmetric Michael Addition

A solution-phase combinatorial approach based on the Ugi four-component reaction was implemented for the development of new prolyl peptide-peptoid hybrid catalysts. Three different elements of diversity were varied during the creation of the set of catalysts: the amine, oxo, and isocyano components. The multicomponent nature of this process enabled the straightforward generation of a series of peptide-peptoid hybrids having the generic sequence Pro-N-R(1)-Xaa-NHR(3), with Xaa being either Gly (R(2) = H) or Aib (R(2) = gem-Me) and R(1) and R(3) either alkyl or amino acid substituents. The catalytic behavior of the peptide-peptoid hybrids was assessed in the asymmetric conjugate addition of aldehydes to nitroolefins, where most of the catalysts showed great efficacy and rendered the Michael adducts with good to excellent enantio- and diastereoselectivity. A molecular modeling study was performed for two distinct catalysts aiming to understand their conformational features. The conformational analysis provided important information for understanding the remarkable stereocontrol achieved during the organocatalytic transformation.

Direct asymmetric Michael addition of phthalide derivatives to chalcones

Abstract The Michael addition of phthalides to chalcones employing a quinidine-derived thiourea catalyst Q-1 has been developed. The reported method led to the synthesis of 3,3-disubstituted phthalide derivatives in excellent yields, with excellent diastereo- and enantioselectivities.

Potassium fluoride: A convenient, non-covalent support for the immobilization of organocatalysts through strong hydrogen bonds

The development of potassium fluoride as a practical non-covalent support for a carboxylic acid containing a pyrrolidine substituent with organocatalytic activity in the asymmetric Michael addition is described. The immobilization is carried out by simply treating the catalytic ligand in dichloromethane (DCM) solution with non-anhydrous potassium fluoride (KF). XRD and FTIR results suggest that the organocatalyst is efficiently loaded onto KF through strong hydrogen bond (SHB) formation, affording the KF-supported catalyst (KF-supCAT, 8) for the direct asymmetric Michael addition of carbonyl compounds to trans-β-nitrostyrenes. Good yields, excellent diastereoselectivities (up to 99:1 syn:anti) and excellent enantioselectivities (up to 97% ee for the syn diastereomer) are recorded in the Michael additions of cyclohexanone to trans-β-nitrostyrenes, considerably improving previous results obtained with a closely related catalyst covalently immobilized onto polystyrene. The KF-supCAT could be recovered and recycled three times by increasing the supersaturation degree of the solution.

Asymmetric Michael addition of 1,3-bis(phenylthio)propan-2-one to nitroalkenes employing Takemoto’s thiourea catalyst

An organocatalytic direct asymmetric Michael addition of bis(phenylthio)propan-2-one to differently substituted aromatic nitroalkenes is described. Takemoto’s thiourea catalyst efficiently promoted this reaction under mild conditions producing the desired products in synthetically useful yields and diastereo- and enantioselectivities. A single crystallization step could further improve the enantiomeric excess up to 98 %.

ChemInform Abstract: C2‐Symmetric Proline‐Derived Tetraamine as Highly Effective Catalyst for Direct Asymmetric Michael Addition of Ketones to Chalcones.

AbstractFor the first time this type of catalyst is effectively applied to the title addition reaction under mild conditions.

Enantioselective Organocatalytic Michael Addition of Ketones to Alkylidene Malonates

Organocatalysts bearing sulfide or sulfone functions (1a-d) were studied for the direct asymmetric Michael addition of ketones and alkylidene malonates. The organocatalyst (S)-2-((naphthalen-2-ylthio)methyl)pyrrolidine, bearing a pyrrolidine and a sulfide moiety, showed a very high catalytic activity in the absence of additives. The reaction condition is mild, and the Michael adducts were obtained in very good enantioselectivities (up to 96%), diastereoselectivities (up to 95:5), and chemical yields (up to 95%).

C2-symmetric proline-derived tetraamine as highly effective catalyst for direct asymmetric Michael addition of ketones to chalcones

A C(2)-symmetric tetraamine catalyst was developed for the asymmetric Michael addition of ketones to chalcones. The corresponding adducts 1,5-dicarbonyl compounds were obtained in good chemical yields with high levels of diastereo- and enantioselectivities (up to >99 : 1 dr and 93% ee) under mild conditions. By studying the ESI-MS of the intermediates, a proposed mechanism was disclosed.

Synthesis and application of L-proline and R-phenylglycine derived organocatalysts for direct asymmetric Michael addition of cyclohexanone to nitroalkenes

Novel R-phenylglycine derived organocatalysts were prepared from the reaction of Cbz-R-phenylglycine with indoline, pyrrolidine, or (S)-(-)-2-(diphenylmethyl)pyrrolidine in 3 steps. The asymmetric Michael addition of cyclohexanone to nitroolefins was investigated using R-phenylglycine derivatives along with L-prolinamides as chiral catalysts. The desired products were obtained in excellent yields with enantioselectivities up to 90% ee and diastereomeric ratio up to 98:2 of the syn }addition product.

ChemInform Abstract: Pyrrolidinyl‐Sulfamide Derivatives as a New Class of Bifunctional Organocatalysts for Direct Asymmetric Michael Addition of Cyclohexanone to Nitroalkenes.

AbstractAsymmetric Michael addition of nitrostyrenes (II) and nitrodiene (IV) towards cyclohexanone is efficiently catalyzed by a novel bifunctional pyrrolidine—sulfamide organocatalyst.

ChemInform Abstract: Direct Asymmetric Michael Addition of Cyclic N‐Sulfonylimines to α,β‐Unsaturated Aldehydes.

AbstractSaccharin‐derived cyclic imines such as (I) can be used as direct nucleophiles in the asymmetric Michael reaction with α,β‐unsaturated aldehydes such as (II) by using the iminium catalyst of a chiral secondary amine.

N,N′-Dioxide–nickel(II) complex catalyzed asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-ketoesters

A direct asymmetric Michael addition of cyclic 1,3-dicarbonyl compounds to β,γ-unsaturated α-ketoesters could be efficiently catalyzed by an N, N′-dioxide–nickel(II) complex. A series of chiral warfarin derivatives were obtained in excellent yields (up to 99%) with high enantioselectivities (up to 90% ee) under mild conditions within shorter reaction time.

Direct Asymmetric Michael Addition of Cyclic N‐Sulfonylimines to α,β‐Unsaturated Aldehydes

Reversal of reactivity: A chemoselective direct asymmetric Michael addition of cyclic N-sulfonylimines to α,β-unsaturated aldehydes has been developed by employing chiral iminium catalysis. A tandem base-catalyzed tautomerization of the imine group/hemiaminal formation/dehydroxylation process of the Michael adducts efficiently affords valuable tricyclic piperidine derivatives in moderate to excellent enantioselectivity.

Pyrrolidinyl-sulfamide derivatives as a new class of bifunctional organocatalysts for direct asymmetric Michael addition of cyclohexanone to nitroalkenes

A series of chiral pyrrolidinyl-sulfamide derivatives have been identified as efficient bifunctional organocatalysts for the direct Michael addition of cyclohexanone to a wide range of nitroalkenes. The desired Michael adducts were obtained in high chemical yields and excellent stereoselectivities (up to 99/1 dr and 95% ee).

ChemInform Abstract: Pyrrolidinyl—Camphor Derivatives as a New Class of Organocatalyst for Direct Asymmetric Michael Addition of Aldehydes and Ketones to β‐Nitroalkenes.

AbstractThe synthetical utility is demonstrated by the synthesis of a tetrasubstituted (XIX) starting from (S)‐citronellal (XVII) with high selectivity.

ChemInform Abstract: Pyrrolidinyl-Camphor Derivatives as a New Class of Organocatalyst for Direct Asymmetric Michael Addition of Aldehydes and Ketones to β-Nitroalkenes.

ChemInform Abstract: Pyrrolidinyl-Camphor Derivatives as a New Class of Organocatalyst for Direct Asymmetric Michael Addition of Aldehydes and Ketones to β-Nitroalkenes.

Pyrrolidinyl–Camphor Derivatives as a New Class of Organocatalyst for Direct Asymmetric Michael Addition of Aldehydes and Ketones to β‐Nitroalkenes

Practical and convenient synthetic routes have been developed for the synthesis of a new class of pyrrolidinyl-camphor derivatives (7 a-h). These novel compounds were screened as catalysts for the direct Michael addition of symmetrical alpha,alpha-disubstituted aldehydes to beta-nitroalkenes. When this asymmetric transformation was catalyzed by organocatalyst 7 f, the desired Michael adducts were obtained in high chemical yields, with high to excellent stereoselectivities (up to 98:2 diastereomeric ratio (d.r.) and 99 % enantiomeric excess (ee)). The scope of the catalytic system was expanded to encompass various aldehydes and ketones as the donor sources. The synthetic application was demonstrated by the synthesis of a tetrasubstituted-cyclohexane derivative from (S)-citronellal, with high stereoselectivity.