Catalytic Enantioselective Michael Addition Reactions Research Articles

Enantioselective direct Michael addition of cyanohydrin ether derivatives to enones catalyzed by chiral bis(guanidino)iminophosphorane organosuperbase.

The direct use of cyanohydrin ether derivatives as less acidic pronucleophiles was achieved for the first time in the catalytic enantioselective Michael addition reaction under transition metal free conditions. Chiral bis(guanidino)iminophosphoranes as the higher order organosuperbase facilitated the intended catalytic Michael addition to enones, giving rise to the corresponding products in high yields with moderate to high diastereo- and enantioselectivities in most cases. Further elaboration of the corresponding enantioenriched product was conducted by derivatization into a lactam derivative through hydrolysis followed by cyclo-condensation.

Catalytic enantioselective Michael addition reactions between in situ detrifluoroacetylatively generated 3-fluorooxindole-derived enolates and 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene

This research presents the first example of catalytic enantioselective Michael addition reactions between 1-(1-(phenylsulfonyl)vinylsulfonyl)benzene and detrifluoroacetylatively in situ generated 3-fluorooxindole-derived enolates. The optimal catalyst includes Cu(OTf)2 and (1S,2S)-1,2-diphenylethane-1,2-diamine featuring NHR functionalities. The reactions are conducted in THF at -20 °C using DIPEA as a base. The additions show reasonably high degree of structural generality and, therefore, synthetic value for preparation of a new family of compounds possessing pharmacophoric 3-fluorooxindole moiety, solofeaturing quaternary C-F stereogenic center.

Catalytic Enantioselective Michael Addition Reactions of Tertiary Enolates Generated by Detrifluoroacetylation.

This work describes, for the first time, Michael addition reactions of tertiary fluoro-enolates in situ generated by detrifluoroacetylation with 1-(1-(phenylsulfonyl) vinylsulfonyl)benzene. Excellent enantioselectivity and chemical yields were achieved with application of catalysts (10 mol %) derived from Cu(OTf)2 and (1S,2S)-1,2-diphenylethane-1,2-diamine. These reactions show a considerable degree of structural generality and allow the preparation of new types of biologically relevant molecules that contain quaternary C-F stereogenic carbon atoms and feature five-, six-, or seven-membered rings as well as heterocyclic 3-fluoro-2,3-dihydrochromen-4-one moieties.

ChemInform Abstract: BINOL—Quinine—Squaramides as Efficient Organocatalysts for the Asymmetric Michael Addition of 2‐Hydroxy‐1,4‐naphthoquinone to Nitroalkenes.

Abstract A set of BINOL–quinine–squaramides were synthesized, and then used as organocatalysts to promote the catalytic enantioselective Michael addition reaction of 2-hydroxy-1,4-naphthoquinone to nitroalkenes with excellent yields and ees (up to 99% yield and 93% ee) at low catalyst loading (0.5 mol %).

BINOL–quinine–squaramides as efficient organocatalysts for the asymmetric Michael addition of 2-hydroxy-1,4-naphthoquinone to nitroalkenes

A set of BINOL–quinine–squaramides were synthesized, and then used as organocatalysts to promote the catalytic enantioselective Michael addition reaction of 2-hydroxy-1,4-naphthoquinone to nitroalkenes with excellent yields and ees (up to 99% yield and 93% ee) at low catalyst loading (0.5mol%).

ChemInform Abstract: 1,3‐Benzodithiole‐1,1,3,3‐tetraoxide (BDT) as a Versatile Methylation Reagent in Catalytic Enantioselective Michael Addition Reaction with Enals.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

1,3-Benzodithiole-1,1,3,3-tetraoxide (BDT) as a versatile methylation reagent in catalytic enantioselective Michael addition reaction with enals

Abstract A protocol of an organocatalytic highly enantioselective conjugate addition of nucleophilic BDT to enals has been developed and the versatile Michael adducts serve as useful building blocks for a variety of organic transformations.

Double Catalytic Enantioselective Michael Addition Reactions of Tertiary Nucleophile Precursors — Tertiary/Quaternary and Quaternary/Quaternary Carbon—Carbon Bond Formations.

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.

Amine-catalyzed Michael reactions of an aminoaldehyde derivative to nitroolefins

Catalytic enantioselective Michael addition reactions of α-amino functionalized aldehydes to nitroolefins have been developed. The Michael product was obtained in up to 98% ee, but the enantiomeric purity of the Michael product was decreased during isolation of the product.

Double catalytic enantioselective Michael addition reactions of tertiary nucleophile precursors—tertiary/quaternary and quaternary/quaternary carbon–carbon bond formations

Enantioselective Michael addition reactions of tertiary nucleophile precursors, such as substituted malononitriles and cyclic 1,3-diketones, can be successfully activated by the metal complexes derived from R, R-DBFOX/Ph chiral ligand and cationic metal salts. With this method, the enantioselective tertiary/quaternary and quaternary/quaternary carbon–carbon bond formations can be achieved. Use of alcohol solvents is essential for the success, and α,β-unsaturated amides of 3,5-dimethylpyrazole are much better acceptors than those of 2-oxazolidinone.

Catalytic, enatioselective Michael addition reactions

This review summarizes the tremendous achievements in the field of catalytic enantioselective Michael addition reaction involving the attack of soft nucleophiles on α,β- unsaturated systems. The reaction has evolved during past two decades, from stoichiometric to catalytic. A large number of efficient catalytic systems have been used to generate chiral Michael adducts in high optical purity. Several chiral alkaloids were used for the enantioselective addition of thiols and dialkylmalonates to cyclic and linear enones to give product in moderate to high enantioselectivity. Chiral crown ethers in conjugation with metal alkoxides were found to be the catalyst of choice for the addition of substituted α-phenylesters to linear enones. Proline derived catalysts gave product in moderate in moderate to high enantioselectivity where NO2 group was present as an activator in either Michael donor or acceptor. BINAP based catalysts were found to be superior in Michael addition of α-nitrile substituted esters to linear enones. A new class of heterobimetallic catalysts based on BINOL ligand was found to be highly versatile for an array of Michael donors and acceptors to provide products in very high optical purity. Metal complexes based on chiral N,N-dioxides were found to be superior for the addition of arylthiols to both linear and cyclic enones to have product in high enantiomeric excess.

ChemInform Abstract: Catalytic Enantioselective Michael Addition Reactions of α‐Nitroesters to α,β‐Unsaturated Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Catalytic enantioselective Michael addition reactions of α-nitroesters to α,β-unsaturated ketones

Enantioselective Michael additions of α-nitroesters 2a-d with α,β-unsaturated ketones were carried out in the presence of a catalytic amount of chiral Al-Li-(R,R′)-2,2′-dihydroxy-1,1′-binaphthyl (‘AlLiBINOL’) complex prepared in situ from LiAlH 4 and 2.45 equiv. of (R,R′)-BINOL. The enantioselectivity of the Michael addition proved to be extremely temperature dependent: Michael adduct 4a showed 7% e.e when the reaction was performed at RT, whereas 72% e.e. of the opposite enantiomer of 4a was found when the 1,4-addition was performed at −23°C. Solvent variation showed that tetrahydrofuran gave the highest selectivity (up to 80% e.e.), whereas the highest enantioselectivity for the opposite enantiomer was found in methylene chloride (up to 25%). X-Ray structure analysis of the AlLi 3BINOL 3 complex 6 in combination with 27Al NMR studies showed that ‘AlLiBINOL’ is a mixture of aluminium complexes in solution.