Enantioselective Cascade Research Articles

Organocatalyzed Michael–Michael Cascade Reaction: Asymmetric Synthesis of Polysubstituted Chromans

An enantioselective cascade Michael-Michael reaction between chalcones enolates and nitromethane catalyzed by a bifunctional thiourea is developed. This reaction provides a mild but efficient approach to chiral benzopyrans bearing three consecutive stereocenters in high yields with excellent stereoselectivities, and the benzopyrans can be easily transformed to the corresponding tricyclic product.

Heterogeneous Bifunctional Catalytic, Chemo‐, Regio‐ and Enantioselective Cascade Inverse Electron Demand Diels–Alder Reaction

AbstractWe present a bifunctional catalytic, chemo‐, regio‐ and enantioselective inverse electron demand Diels–Alder reaction (IEDDAR) cascade of a variety of methylenebut‐3‐enoates with azlactones at high levels of yield and enantioselectivity (up to 99% yield, and >99% ee) via a dual HOMOdienophiles and LUMOdienes activated pathway using a heterogeneous catalytic system. Meanwhile, a novel MNPs‐supported chiral thiourea was developed for economical and environment‐friendly purposes. The catalyst can be conveniently recycled and reused for 10 runs with only a slight loss of yield and enantioselectivity.

Cinchona-based squaramide-catalysed cascade aza-Michael–Michael addition: enantioselective construction of functionalized spirooxindole tetrahydroquinolines

An efficient enantioselective cascade aza-Michael-Michael addition reaction catalysed by a chiral bifunctional tertiary amine-squaramide catalyst has been developed. This cascade reaction proceeded well under mild conditions, furnishing highly functionalized spirooxindole tetrahydroquinolines with three contiguous stereocenters in excellent yields with excellent diastereoselectivities (>25:1 dr) and high enantioselectivities (up to 94% ee).

Highly enantioselective cascade transformations by merging heterogeneous transition metal catalysis with asymmetric aminocatalysis.

The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30:1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.

ChemInform Abstract: New Approach to the Preparation of Bicyclo Octane Derivatives via the Enantioselective Cascade Reaction Catalyzed by Chiral Diamine‐Ni(OAc)2 Complex.

AbstractA simple and highly efficient reaction of various 1,2‐diones with substituted nitroalkenes is reported.

ChemInform Abstract: Asymmetric Organocatalytic Cascade Michael/Michael/Henry Reaction Sequence: Control of All Stereocenters in One Cyclohexane Skeleton.

AbstractHexasubstituted chiral cyclohexanols are constructed in one step.

ChemInform Abstract: Inter‐ and Intramolecular Carbon—Carbon Bond‐Forming Radical Reactions

AbstractReview: ca. 150 refs.

ChemInform Abstract: One‐Step Catalytic Enantioselective α‐Quaternary 5‐Hydroxyproline Synthesis: An Asymmetric Entry to Highly Functionalized α‐Quaternary Proline Derivatives.

The highly enantioselective cascade reaction between N-protected a-cyanoglycine esters and a,beta-unsaturated aldehydes is disclosed. The reaction represents a one-step entry to polysubstituted 5-h ...

Inter- and Intramolecular Carbon-Carbon Bond-Forming Radical Reactions

Free-radical-mediated reactions were studied as a powerful method for constructing the carbon–carbon bond. The intermolecular carbon radical addition to ketimines has not been widely studied. The screening of reactive ketimino radical acceptors showed that ketimines having a 2-phenolic hydroxyl group exhibit good reactivities toward nucleophilic alkyl radicals. The radical addition of these ketimines took place regioselectively at the imino carbon, providing a novel method for the construction of all-substituted sp3-hybridized carbon centers. We also found that the pyruvic hydrazone and isatin hydrazone show excellent reactivities to afford the corresponding C-alkylated products. Enantio- or diastereoselective radical addition reaction of ketimines was also tested. The control of stereochemistry in cyclization reactions has been of great importance to radical chemistry. As a cyclization that provides highly functionalized cyclic compounds, the diastereoselective cyclizations of oxime ethers were investigated. The diastereoselective radical cyclizations proceeded through a conformer that minimizes the A1,3-strain effect, and the configuration of the alkoxyamino group on the products was highly controlled by the 1,2-stereoinduction. Next, the chiral Lewis acid mediated enantioselective cyclization reactions were studied. Stereocontrol in the radical addition–cyclization–trapping reaction was achieved by the new approach, which employs hydroxamate ester functionality as a chiral Lewis acid coordinating tether between two radical acceptors. The enantioselective cascade reaction of oxime ethers also proceeded smoothly with good enantio- and diastereoselectivities. Recently, we have developed cascade reactions starting from the polarity-mismatched perfluoroalkylation of an electron-deficient acceptor with electrophilic perfluoroalkyl radicals. These cascade reactions provide a novel approach to the asymmetric synthesis of various γ-lactams. 1 Introduction 2 Intermolecular Radical Addition to Imine Derivatives 2.1 Effect of a Phenolic Hydroxyl Group on the Reaction of ­Aldimine 2.2 Reactivity of Ketimines Having a Phenolic Hydroxyl Group 2.3 Screening of Other Ketimino Radical Acceptors 3 Stereocontrolled Radical Cyclization 3.1 Diastereoselective Cyclization of Oxime Ethers 3.2 Stereocontrol by Using a Chiral Lewis Acid 3.3 Enantioselective Cascade Reaction of Oxime Ethers 3.4 Cyclization Induced by Polarity-Mismatched Perfluoro­alkylation 4 Conclusion

Direct catalytic asymmetric synthesis of pyrazolidine derivatives.

A highly enantioselective, metal-free cascade reaction between di-1,2-N-protected hydrazine and α,β-unsaturated aldehydes is disclosed. The catalytic, asymmetric cascade transformation is a direct ...

One‐Step Catalytic Enantioselective α‐Quaternary 5‐Hydroxyproline Synthesis: An Asymmetric Entry to Highly Functionalized α‐Quaternary Proline Derivatives

AbstractThe highly enantioselective cascade reaction between N‐protected α‐cyanoglycine esters and α,β‐unsaturated aldehydes is disclosed. The reaction represents a one‐step entry to polysubstituted 5‐hydroxyproline derivatives having a quaternary α‐stereocenter generally in high yields with up to >95:5 dr and 99:1 er. It is also a direct catalytic two‐step entry to functionalized α‐quaternary proline derivatives.

ChemInform Abstract: Enantioselective Cascade Sequence to Indoloquinolizidines and Its Application in the Synthesis of epi‐Geissochizol.

AbstractMichael addition of the tethered indole (I) to unsaturated aldehydes followed by Pictet—Spengler reaction yields indolo[2,3‐a]quinolizidine intermediates which are reductively converted to products (III) or (V).

Enantioselective Cascade Reactions of Stable Sulfur Ylides and Nitroolefins through an Axial-to-Central Chirality Transfer Strategy

An enantioselective [4 + 1] annulation/rearrangement cascade of stable sulfur ylides and nitroolefins has been developed through an efficient axial-to-central chirality transfer with the use of a chiral BINOL-derived sulfide as a reliable stereocontroller. It can provide pharmaceutically and synthetically important oxazolidinones in high stereoselectivities (up to 96:4 e.r. and >95:5 d.r.). Moreover, this strategy was also successfully applied to the asymmetric [4 + 1]/[3 + 2] cycloaddition cascade of sulfur ylides with alkene-tethered nitroolefins, and the corresponding enantioenriched fused heterocycles (up to 87:13 e.r. and >95:5 d.r.) were obtained in good to excellent yields (54-95% yields).

New approach to the preparation of bicyclo octane derivatives via the enantioselective cascade reaction catalyzed by chiral diamine-Ni(OAc)2 complex

A highly efficient catalyst system assembled from enantiomerically pure diaminocyclohexane and Ni(OAc)(2) is, for the first time, used to catalyze the cascade Michael-Henry reaction of various diones and substituted nitroalkenes. A series of polyfunctionalized bicyclo[3.2.1]octane derivatives containing four stereogenic centers are prepared with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (up to 50 : 1 dr) with high yields. In addition, via this chiral diamine-Ni(OAc)(2) catalyst system, the base-induced epimerization leading to the decrease of stereoselectivity can be prevented.

Enantioselective Cascade Sequence to Indoloquinolizidines and Its Application in the Synthesis of epi-Geissochizol

An organocatalyzed one-pot Michael addition and Pictet-Spengler sequence utilizing beta-keto amide and aliphatic alpha,beta-unsaturated aldehydes was developed, which provided access to highly substituted indolo[2,3-a]quinolizidines as a mixture of keto and enol tautomers. Such tautomeric pairs were transformed into stable compounds with an E-ethylidenyl group in telescoped steps. This method was successfully applied in the synthesis of epi-geissoschizol.

ChemInform Abstract: Interplay of Direct Stereocontrol and Dynamic Kinetic Resolution in a Bifunctional Amine Thiourea Catalyzed Highly Enantioselective Cascade Michael—Michael Reaction.

ChemInform Abstract: Interplay of Direct Stereocontrol and Dynamic Kinetic Resolution in a Bifunctional Amine Thiourea Catalyzed Highly Enantioselective Cascade Michael—Michael Reaction.

Organocatalytic enantioselective β-functionalization of aldehydes by oxidation of enamines and their application in cascade reactions

Iminium catalysis, involving the transformation of iminium ions to enamines, has been extensively studied in the context of a number of organic processes. However, the reverse of this process involving conversion of enamines to iminium species has not been realized. Here, we describe a new transformation-'oxidative enamine catalysis'-in which direct oxidation of an enamine occurs to generate an iminium species. We show that the use of o-iodoxybenzoic acid as an oxidant in the presence of a secondary amine catalyst serves as effective system for promoting rapid conversion of enamines to iminium ions. The preparative power of this process has been demonstrated in the context of direct asymmetric β-functionalization of simple aldehydes. Moreover, a variety of enantioselective cascade transformations, including triple and quadruple cascades, have been developed for the 'one-pot' synthesis of versatile chiral building blocks and structural frameworks starting with simple aldehydes.

Enantioselective Synthesis of Chromans with a Quaternary Stereogenic Centre through Catalytic Asymmetric Cascade Reactions

A highly enantioselective cascade reaction of benzotriazoles with nitroolefin-containing enonates catalyzed by a base/acid bifunctional organocatalyst has been developed. This cascade sequence affo...

An efficient and recyclable hybrid nanocatalyst to promote enantioselective radical cascade rearrangements of enediynes

Mesoporous silica grafted with a tertiary amine was used as a basic nanocatalyst to promote in confined medium the enantioselective cascade rearrangement of enediynes based on the phenomenon of memory of chirality; the multi-substrates recyclable catalytic reagent could easily be recovered by simple filtration, and reused without any decrease in activity even when changing the solvent.

Interplay of Direct Stereocontrol and Dynamic Kinetic Resolution in a Bifunctional Amine Thiourea Catalyzed Highly Enantioselective Cascade Michael–Michael Reaction

Control is better: A novel chiral amine thiourea catalyzed, highly enantioselective Michael–Michael cascade process serves as a “one-pot” approach to synthetically and biologically significant chiral tetrahydrothiophenes (see scheme). Notably, an unprecedented cooperative direct stereocontrol and dynamic kinetic resolution by the bifunctional catalyst is identified that governs the highly enantioselective cascade process. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.