Vinylogous Mannich Reaction Research Articles

ChemInform Abstract: Cinchona Alkaloid Amide/Copper(II) Catalyzed Diastereo‐ and Enantioselective Vinylogous Mannich Reaction of Ketimines with Siloxyfurans.

AbstractThe asymmetric vinylogous Mannich reaction of unactivated ketimines with siloxyfurans using cinchona alkaloids and Cu(OAc)2 as catalysts is reported.

Recent Advances in Metal-Catalyzed Asymmetric Mannich Reactions

In this review, recent works on metal-catalyzed asymmetric Mannich, aza-Henry and vinylogous Mannich reactions are described. The asymmetric Mannich reaction is one of the most powerful methodologies among the carbon–carbon bond-forming reactions, and provides direct access to a wide range of optically active natural products with useful biological properties. 1 Introduction 2 Catalytic Asymmetric Mannich Reactions 2.1 BINOL Ligands 2.2 BINAP Ligands 2.3 Bisoxazoline Ligands 2.4 Pyridine Bisoxazoline Ligands 2.5 Diamine Ligands 2.6 P,N-Ligands 2.7 P,S-Ligands 2.8 P,P-Ligands 2.9 N,N-Ligands 2.10 Miscellaneous 3 Asymmetric Aza-Henry Reactions 3.1 BINOL Ligands 3.2 Bisoxazoline Ligands 3.3 N,N-Ligands 3.4 Miscellaneous 4 Asymmetric Vinylogous Mannich Reactions 5 Conclusion

New silver(I)–monophosphine complex derived from chiral Ar-BINMOL: synthesis and catalytic activity in asymmetric vinylogous Mannich reaction

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.

Cinchona Alkaloid Amide/Copper(II) Catalyzed Diastereo‐ and Enantioselective Vinylogous Mannich Reaction of Ketimines with Siloxyfurans

The asymmetric vinylogous Mannich reaction of unactivated ketimines with siloxyfurans using cinchona alkaloids and Cu(OAc)2 as catalysts is reported.

Cinchona Alkaloid Amide/Copper(II) Catalyzed Diastereo‐ and Enantioselective Vinylogous Mannich Reaction of Ketimines with Siloxyfurans

Cinchona Alkaloid Amide/Copper(II) Catalyzed Diastereo‐ and Enantioselective Vinylogous Mannich Reaction of Ketimines with Siloxyfurans

High diastereoselective vinylogous Mannich reaction induced by O-pivaloylated d-galactosylamine as the chiral auxiliary: stereoselective synthesis of 8-arylazocan-2-one

The diastereospecific formation of β-N-glycosidically linked α,β-unsaturated δ-amino aldehyde derivatives has been achieved with high yield via a vinylogous Mannich reaction. The reaction was performed by using a O-pivaloylated galactosyl amine as a chiral template and AlCl3 as a promoter in THF. (S)-8-(p-Nitrophenyl) azocan-2-one can be stereoselective synthesized from (S) ethyl 7-galactosylamino-7-(p-nitrophenyl)hepta-2,4-dienoate by sequential hydrogenation of the double bond, cyclic lactam formation, and removal of the N-glycosidic auxiliary under basic conditions.

A Concise and Divergent Approach to Hydroxylated Piperidine Alkaloids and Azasugar Lactams

AbstractThe vinylogous Mannich reaction (VMR) between 2‐(tert‐butyldimethylsilyloxy)furan (TBSOF) and (RS)‐t‐BS‐imine 12a and the application of the VMR adduct butenolide 13a as a versatile chiral building block for the synthesis of hydroxylated piperidine alkaloids and azasugars were investigated. Firstly, both the anti diastereoselectivity and the chemical yield of the asymmetric VMR between TBSOF and (RS)‐t‐BS‐imine 12a were improved by the use of Sm(OTf)3/H2O (1.5 equiv.) as the promoter. Similar diastereoselectivities were also obtained with Yb(OTf)3/H2O, Cu(OTf)2/H2O, Zn(OTf)2/H2O, or the Brønsted acids TfOH or MsOH as the promotors. Secondly, an efficient four‐step procedure for the elaboration of butenolide 13a into piperidine alkaloid (–)‐deoxoprosophylline (2) was established. Thirdly, by taking advantage of the olefin functionality in the butenolide 13a, polyhydroxylated δ‐lactams 23 and 21, which are ready precursors of azasugars L‐deoxyallonojirimycin (ent‐7) and L‐3‐epi‐fagomine (ent‐6), were obtained in two and three steps, respectively, via dihydroxylated lactone 17. The easily available synthetic intermediate 17 can also serve as a key intermediate for the synthesis of the glycosyl nucleoside amino acid cores of polyoxins and nikkomycins.

ChemInform Abstract: Direct Asymmetric Vinylogous Mannich Reaction of 3,4‐Dihalofuran‐2(5H)‐one with Aldimine Catalyzed by Quinine.

AbstractFuranones of type (III) are useful synthons which can be converted into optically active butyrolactones such as (IV) and amino diols like (V).

A General Organocatalytic Approach toward the Enantioselective Total Synthesis of Indolizidine Based Alkaloids

Four indolizidine based alkaloids (IBAs) have been synthesized in a highly enantioselective, straightforward, and flexible manner. As a key step our previously developed Brønsted acid catalyzed vinylogous Mannich reaction was employed which easily afforded gram amounts of an optically pure central intermediate which can be converted into a wide range of diversely substituted IBAs.

ChemInform Abstract: Facile and Highly Diastereoselective Synthesis of 3‐Aminooxindoles via AgOAc‐Catalyzed Vinylogous Mannich Reaction.

Abstract A novel AgOAc-catalyzed vinylogous Mannich reaction between easily prepared imines 1 derived from isatins and trimethylsilyloxyfuran 2 (TMSOF) was developed. This method provided a facile synthetic route to get access to synthetically useful quaternary 3-aminooxindole in excellent yields (94–99%) and diastereoselectivities (>99:1).

Direct Asymmetric Vinylogous Mannich Reaction of 3,4-Dihalofuran-2(5H)-one with Aldimine Catalyzed by Quinine

The direct asymmetric vinylogous Mannich reaction of 3,4-dihalofuran-2(5H)-one with aldimine catalyzed by quinine was first reported, and γ-butenolides have been obtained in excellent yield (up to 98%) and enantioselectivities (up to 95% ee). The synthetic applications of this protocol are demonstrated in the preparations of γ-substituted amino butyrolactones and vicinal amino alcohols.

An Asymmetric Organocatalytic Povarov Reaction with 2-Hydroxystyrenes

An organocatalytic asymmetric three-component Povarov reaction involving 2-hydroxystyrenes has been established to provide an efficient method to access structurally diverse cis-disubstituted tetrahydroquinolines in high stereoselectivities of up to >99:1 dr and 97% ee. This protocol also provides an easy access to tetrahydroquinolines with chiral quaternary stereocenters upon using α-alkyl 2-hydroxystyrenes as substrates. The theoretical studies revealed that the Povarov reaction proceeded through a sequential vinylogous Mannich reaction and an intramolecular Friedel-Crafts reaction, wherein the phosphoric acid acted as bifunctional catalyst to activate 2-hydroxystyrene and aldimine simultaneously.

ChemInform Abstract: A Modified and Highly Useful Protocol for the Broensted Acid Catalyzed, Enantioselective, Vinylogous Mannich Reaction with Aliphatic Aldimines.

AbstractThe optimized protocol is developed for the enantio‐ and diastereoselective synthesis of esters (IV) and (VIII).

ChemInform Abstract: Lewis Acid Catalyzed Diastereoselective Vinylogous Mannich Reaction Induced by O‐Pivaloylated D‐Galactosylamine as the Chiral Auxiliary: Stereoselective Synthesis of 6‐Arylpiperidin‐2‐ones.

AbstractUnder optimized conditions with FeCl3 as the catalyst, the reaction of galactosyl derived aldimines with silyl dienolate proceeds with good to excellent diastereoselectivity.

Facile and highly diastereoselective synthesis of 3-aminooxindoles via AgOAc-catalyzed vinylogous Mannich reaction

A novel AgOAc-catalyzed vinylogous Mannich reaction between easily prepared imines 1 derived from isatins and trimethylsilyloxyfuran 2 (TMSOF) was developed. This method provided a facile synthetic route to get access to synthetically useful quaternary 3-aminooxindole in excellent yields (94–99%) and diastereoselectivities (>99:1).

Lewis Acid Catalyzed Diastereoselective Vinylogous Mannich Reaction Induced by O-Pivaloylated d-Galactosylamine as the Chiral Auxiliary: Stereoselective Synthesis of 6-Arylpiperidin-2-ones

The diastereospecific formation of β-N-glycosidically linked α,β-unsaturated δ-aminocarbonyl derivatives, in the form of (S)-δ-amino-δ-arylpent-2-enoic ester, has been achieved in high yield via a vinylogous Mannich reaction, utilizing poly-O-pivaloylated d-galacosylamine as the chiral auxiliary. (S)-6-p-Tolylpiperidine-2-one can be stereoselectively synthesized from (S)-δ-amino-δ-arylpent-2-enoic ester by sequential hydrogenation of the double bond, cyclic lactam formation, and removal of the N-glycosidic auxiliary under basic conditions.

A Modified and Highly Useful Protocol for the Brønsted Acid Catalyzed, Enantioselective, Vinylogous Mannich Reaction with Aliphatic Aldimines

Highly enantioselective as well as diastereoselective catalytic vinylogous Mannich reactions have been accomplished for the first time with aliphatic straight-chain aldimines and O,O-silylketene acetals and furnish valuable synthetic building blocks in high enantiomeric purity.

Concise Asymmetric Total Synthesis of 9-epi-Sessilifoliamide J

A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with sessilifoliamide J (6), has been accomplished from the key chiral building block 11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)-mediated coupling lactonization. The absolute configuration of the natural sessilifoliamide J was established.

Asymmetric Vinylogous Mannich Reactions: A Versatile Approach to Functionalized Heterocycles

Asymmetric vinylogous Mannich reaction (VMR) of 2-(tert-butyldimethylsilyloxy)furan (TBSOF, 1) with (R(S))- or (S(S))-t-BS-imines (3) furnished 5-aminoalkylbutenolides 7a-k in 75-87% yields with anti/syn ratios ranging from 75:25 to 97:3. Butenolides 7a-f,k were readily converted into substituted lactones 8 and 5 and 6-substituted 5-hydroxypiperidin-2-ones 11a-g, which are, in turn, key intermediates for the synthesis of many bioactive compounds.

ChemInform Abstract: Highly Diastereo‐ and Enantioselective Vinylogous Mannich Reactions of Fluorinated Aldimines with Siloxyfurans.

A highly regio- and enantioselective asymmetric vinylogous Mannich reaction of readily available fluorinated aldimines bearing a chiral auxiliary [(S)-1-phenylethyl group] with siloxyfurans to afford chiral fluorine-containing γ-butenolide or γ-lactone derivatives has been developed in the presence of silver acetate (10 mol%) and axially chiral phosphine-oxazoline ligand L1 (11 mol%). In most cases, the corresponding fluorinated adducts were obtained in high yields, good to excellent enantiomeric excesses and up to > 20:1 dr.