Asymmetric Vinylogous Mannich Reaction Research Articles

Copper-Catalyzed Direct Asymmetric Vinylogous Mannich Reaction between β,γ-Alkynyl-α-ketimino Esters and β,γ-Unsaturated N-Acylpyrazoles.

We report a Cu(I)-Ph-BPE-catalyzed asymmetric vinylogous Mannich reaction of β,γ-alkynyl-α-ketimino esters with β,γ-unsaturated N-acylpyrazoles. In this process, the Cu(I)-Ph-BPE catalyst activates the β,γ-alkynyl-α-ketimino ester through N,O-coordination, enabling the subsequent nucleophilic addition of a dienolate generated from the β,γ-unsaturated N-acylpyrazole via α-position deprotonation with a catalytic amount of tertiary amine. The reactions gave useful products with very high enantioselectivities. A broad range of substrates with various substituents are tolerated in this reaction. The versatility of this method was demonstrated by a gram-scale reaction, and subsequent elaboration of the Mannich adducts was also provided.

Borane-Catalyzed Direct Asymmetric Vinylogous Mannich Reactions of Acyclic α,β-Unsaturated Ketones.

Herein, we report that, by using chiral bicyclic bisborane catalysts, we have achieved the first highly regio-, diastereo-, and enantioselective direct asymmetric vinylogous Mannich reactions of acyclic α,β-unsaturated ketones. The strong Lewis acidity and steric bulk of the bisborane catalysts were essential for the observed high yields and selectivities.

Direct Asymmetric Vinylogous Mannich Reactions of Acyclic α,β-Unsaturated Ketones Catalyzed by Chiral Boranes

Direct Asymmetric Vinylogous Mannich Reactions of Acyclic <i>α</i>,<i>β</i>-Unsaturated Ketones Catalyzed by Chiral Boranes

Amide‐phosphonium Salt Catalyzed Enantioselective Vinylogous Mannich Addition of Coumarins to Isatin Imines

AbstractAn asymmetric vinylogous Mannich reaction between 3‐cyano‐4‐methylcoumarins and N‐Boc isatin imines catalysed by amide phosphonium salt is described. This method allows the formation of intriguing adducts bearing both 3‐aminooxindole and coumarin moieties in excellent yields with excellent enantioselectivities. The utility of this method was illustrated by a gram scale synthesis using as low as 0.1 mol % of catalyst without chromatographic purification, and removal of the Boc protecting groups on the primary amine functionality in Mannich products.

The asymmetric vinylogous Mannich reaction of noncyclic dicyanoolefins catalyzed by a bifunctional thiourea–ammonium salt phase transfer catalyst

An efficient enantioselective vinylogous Mannich reaction of N-Boc aminosulfones with noncyclic α,α-dicyanoolefins has been realized using an extraordinary bifunctional thiourea–ammonium salt phase transfer catalyst derived from quinine.

Chiral VAPOL Imidodiphosphoric Acid-Catalyzed Asymmetric Vinylogous Mannich Reaction for the Synthesis of Butenolides

Chiral butenolides were synthesized by the enantioselective vinylogous Mannich reaction. Chiral (VAPOL)-type imidodiphosphoric acids are efficient catalysts for the asymmetric vinylogous Mannich (AVM) reaction of aldimines and trimethylsiloxyfuran in toluene. Under the optimized conditions, a series of butenolides were obtained with high yields (up to 98%) and enantioselectivities (up to 97% ee) as well as excellent diastereoselectivities (up to 99:1 dr).

Asymmetric Vinylogous Mannich‐Type Addition of α,α‐Dicyanoalkenes to α‐Fluoroalkyl Sulfinyl Imines

AbstractThe asymmetric vinylogous Mannich reaction (AVMR) of α,α‐dicyanoalkenes with α‐fluoroalkyl sulfinyl imines has been successfully accomplished. This transformation is unprecedented with fluorinated imines and, at the same time, the use of dicyanoalkenes in AVMR has been scarcely reported. Several fluorinated sulfinyl imines are compatible with the process, which gives access to a family of chiral fluorinated amines with an excellent level of stereocontrol. Interestingly, the selectivity found in our protocol is the opposite of that encountered in analogous, previously reported AVMRs. Additionally, the synthetic applicability of the addition products has been exemplified with several transformations showing the particular reactivity of the dicyanoalkene moiety of these α‐fluorinated amines.magnified image

Progress in Heterocycles-Based Asymmetric Vinylogous Mannich Reactions and Applications to the Synthesis of Alkaloids

Progress in Heterocycles-Based Asymmetric Vinylogous Mannich Reactions and Applications to the Synthesis of Alkaloids

An asymmetric organocatalytic vinylogous Mannich reaction of 3-methyl-5-arylfuran-2(3H)-ones with N-(2-pyridinesulfonyl) imines: enantioselective synthesis of δ-amino γ,γ-disubstituted butenolides.

An asymmetric organocatalytic vinylogous Mannich reaction of 3-methyl-5-arylfuran-2(3H)-ones with N-(2-pyridinesulfonyl)imines has been developed with 5 mol% thiourea-tertiary amine as the catalyst. A series of δ-amino γ,γ-disubstituted butenolides bearing adjacent quaternary and tertiary stereocenters are efficiently obtained with satisfactory results (up to 90% yield, 90 : 10 dr, and 95 : 5 er).

Synthetic versatility of 2-substituted-6-methyl 2,3-dihydropyridinones in the synthesis of polyfunctional piperidine-based compounds and related β amino acid derivatives.

Chiral 2-substituted-6-methyl 2,3-dihydropyidinones 9, which can be facilely obtained from an asymmetric vinylogous Mannich reaction (VMR) with 1,3-bis-trimethysily enol ether, were used as versatile intermediates in constructing chiral polyfunctional piperidine-based compounds. The 6-methyl group of such compounds can be conveniently functionalized via alkylation and acylation reactions to provide efficient entries to the synthesis of a variety of chiral multi-substituted piperidine-based compounds. Further elaboration of the corresponding intermediates also provided access to polyfunctional indolizidine-based compounds. These methods were showcased in an asymmetric synthesis of 2,6-di-substituted piperidine compound 13, reported as the key intermediate in the synthesis of (+)-calvine and a natural alkaloid (-)-indolizidine 209D. Furthermore, selective C5 iodination of compound 9 enabled the installation of additional functional groups at this position. Finally, we demonstrated that the oxidative cleavage of 2-substituted-6-methyl-2,3-dihydropyidinones is a practical and efficient method for the enantioselective synthesis of β-amino acids, which can undergo further intra-molecular cyclization to give the corresponding chiral four-membered β-lactam derivatives.

Effective asymmetric vinylogous Mannich reaction of isatin imines with α,α-dicyanoolefins in the presence of a simple chiral amide phosphonium bifunctional phase transfer catalyst

A Mannich reaction between N-Boc isatin imine and α,α-dicyanoolefin as well as subsequent oxidative cleavage of the malonic nitrile moiety were described.

ChemInform Abstract: A Decade of Advance in the Asymmetric Vinylogous Mannich Reaction

AbstractReview: [70 refs.

ChemInform Abstract: A Versatile Access to Vicinal Diamine Motifs by Highly anti‐Selective Asymmetric Vinylogous Mannich Reactions: An Efficient Total Synthesis of (+)‐Absouline.

AbstractThe vicinal diamine motif (Vd) is utilized in the efficient total synthesis of (+)‐absouline (VI).

A Decade of Advance in the Asymmetric Vinylogous Mannich Reaction

When the principle of vinylogy is applied to imines as electrophiles, the so-called vinylogous Mannich reaction (VMR), γ-aminocarbonyl (such as butenolides) and β-aminocarbonyl compounds are generated in a very efficient manner. The asymmetric version of this vinylogous Mannich reaction gives access to highly functionalized chiral synthons, which are suitable for further transformations. The versatility of this methodology is exemplified with the synthesis of several alkaloids and natural products. 1 Introduction 2 Asymmetric Vinylogous Mannich Reactions (VMR) with 2-Silyl­oxyfurans and 2-Silyloxypyrroles 3 Asymmetric VMR with Acyclic Silyl Dienolates and Silyl Dienol Ketene Acetals 4 Asymmetric VMR with γ-Butenolides and γ-Butyrolactams 5 Asymmetric VMR with α,α-Dicyanoolefins 6 Miscellaneous Donors in Asymmetric VMR 7 Application of the VMR to Natural Product Synthesis 8 Conclusions

Studies on the Second-Generation Approach to Loline Alkaloids: Synthesis of N-Bus-norloline through N-tert-Butanesulfinyl Imine Based Asymmetric Vinylogous Mannich Reaction

A strategy is outlined for the synthesis of loline alkaloids. This second-generation approach features direct access to the requisite vicinal diamino motif by a Cu(OTf)₂-mediated highly <i>trans</i>-diastereoselective vinylogous Mannich reaction (VMR) of Ellman <i>N</i>-<i>tert</i>-butanesulfinyl imine derived from isopropylidene-protected (<i>S</i>)-glyceraldehyde, with <i>N</i>-Boc-2-<i>tert</i>-(butyldimethylsilyloxy)pyrrole (TBSOP). Fleming’s method was employed for the introduction of a hydroxyl group at C4 of the adduct, which gave the undesired diastereomer in 40% yield. The intramolecular S_N reaction of the pyrrolizidine derivative to build the etheral bridge proved to be difficult, and produced <i>N</i>-Bus-norloline in only 20% yield. In light of the valuable information gained during this investigation, an improved version of the second-generation approach is being investigated, which is expected to provide a concise and efficient access to the challenging loline alkaloids.

A versatile access to vicinal diamine motifs by highly anti-selective asymmetric vinylogous Mannich reactions: an efficient total synthesis of (+)-absouline

An anti-stereoselective vinylogous Mannich reaction between 2-TBSO-pyrrole and N-tert-butanesulfinyl imines and its application to the efficient synthesis of (+)-absouline were reported.

ChemInform Abstract: Organocatalytic Direct Asymmetric Vinylogous Mannich Reaction of γ‐Butenolides with Isatin‐Derived Ketimines.

AbstractThe title reaction proceeds in the presence of quinidine‐derived catalyst to form 3‐aminooxindole derivatives with moderate diastereoselectivities and high enantioselectivities.

ChemInform Abstract: 2‐Chlorotetrafluoroethanesulfinamide Induced Asymmetric Vinylogous Mannich Reaction.

AbstractThe generality of (S)‐2‐chlorotetrafluoroethanesulfinamide (I) induced asymmetric vinylogous Mannich addition reaction is investigated.

ChemInform Abstract: New Silver(I)—Monophosphine Complex Derived from Chiral Ar‐BINMOL: Synthesis and Catalytic Activity in Asymmetric Vinylogous Mannich Reaction.

Abstract A new family of C2-axially chiral monophosphines (Ar-NNPs) from Ar-BINMOLs was developed for silver-catalyzed asymmetric vinylogous Mannich reaction of (furan-2-yloxy)trimethylsilane with aromatic aldimines. It was found that the enantioselective vinylogous Mannich-type reactions of trimethylsiloxyfuran with aldimines are catalyzed efficiently by silver(I) complexes of the Ar-BINMOL-derived chiral monophosphine. This procedure displays wide aldimine versatility, excellent yields (up to 99% isolated yields), moderate to good enantioselectivity (up to 78%ee) and exceptional diastereoselectivity (>99:1 dr) in most cases examined. The molecular structure of silver–monophosphine complex was confirmed by X-ray analysis and revealed that the benzyl group on chiral monophosphine provided dual function with weak silver–π/π–π stacking and steric repulsion to favour the diastereoselective Re-nucleophilic addition of siloxyfuran to imine.

Organocatalytic direct asymmetric vinylogous Mannich reaction of γ-butenolides with isatin-derived ketimines

The first direct asymmetric vinylogous Mannich reaction of γ-butenolides with isatin-derived ketimines has been effectively realized promoted by a bifunctional quinidine-derived catalyst. A series of chiral 3-aminooxindole derivatives bearing adjacent tertiary and quaternary stereocenters with the butenolide moiety were obtained in excellent yields (up to 97%) and high enantioselectivities (up to 96% ee).