Mannich Addition Reactions Research Articles

Regio- and Diastereoselective Vinylogous Mannich Addition of 3-Alkenyl-2-oxindoles to α-Fluoroalkyl Aldimines

An efficient asymmetric vinylogous Mannich (AVM) addition reaction of 3-alkenyl-2-oxindoles to α-fluoroalkyl aldimines has been developed. This reaction provided various optical active α-alkylidene-δ-amino-δ-fluoroalkyl oxindoles in excellent yields, complete γ-site ­regioselectivity, and excellent diastereoselectivities.

Synthesis of (2S,3S)-β-(trifluoromethyl)-α,β-diamino acid by Mannich addition of glycine Schiff base Ni(II) complexes to N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine

A convenient access to (2S,3S)-β-(trifluoromethyl)-α,β-diamino acid is reported by using highly diastereoselective Mannich addition reactions of either chiral or achiral Ni(II) complexes derived from glycine Schiff bases to a chiral sulfinimine, N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine. Disassembly of the resultant Ni(II) complexes affords the target amino acid which was, for the first time, isolated in enantiomerically pure form and fully characterized.

ChemInform Abstract: Asymmetric Synthesis of β′‐Amino‐α,β‐enones via Addition of α,β‐Unsaturated Ketone‐Derived Enolates to Chiral N‐Phosphonyl Imines.

Abstract Efficient asymmetric Mannich addition reactions between α,β-unsaturated ketone derived enolates and N -phosphonyl imines were reported. These reactions could proceed smoothly for a variety of imine substrates with good (up to 96%) chemical yields and excellent diastereoselectivities (up to 98:2 dr). The method reported in this work provides an easy access to chiral β′-amino-α,β-enones.

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

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

Asymmetric synthesis of β′-amino-α,β-enones via addition of α,β-unsaturated ketone-derived enolates to chiral N-phosphonyl imines

Efficient asymmetric Mannich addition reactions between α,β-unsaturated ketone derived enolates and N-phosphonyl imines were reported. These reactions could proceed smoothly for a variety of imine substrates with good (up to 96%) chemical yields and excellent diastereoselectivities (up to 98:2 dr). The method reported in this work provides an easy access to chiral β′-amino-α,β-enones.

2-Chlorotetrafluoroethanesulfinamide induced asymmetric vinylogous Mannich reaction

The generality of (S)-2-chlorotetrafluoroethanesulfinamide (CTFSA) induced asymmetric vinylogous Mannich (AVM) addition reaction has been investigated. The reaction of aldimines derived from (S)-CTFSA with 2-(tert-butyldimethylsilyloxy) furan (TBSOF) took place regioselectively at the γ-site at room temperature in DMSO under air atmosphere to give the desired addition products in syn-configuration with high diastereoselectivities (up to 98:2 dr). However, anti-configuration product as major isomer was obtained in the presence of tetra-butyl ammonium fluoride (TBAF) at −78 °C. Facile removal of the auxiliary group without epimerization demonstrated their synthetic potential for piperidone derivatives.

Asymmetric Mannich reaction between (S)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine and malonic acid derivatives. Stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids

Inorganic as well as organic base catalysis was found to be effective for diastereoselective Mannich additions of malonic acid derivatives to (SS)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine. In the presence of catalytic amounts of inorganic bases, n-BuLi or DMAP, the reaction gives the corresponding (R,SS)-β-aminomalonates in good yield and with diastereoselectivity up to 9/1 dr. In contrast, phosphazene bases favour the formation of the (S,SS)-diastereomer with selectivities as high as 99/1. Simple choosing of an appropriate base catalyst for the Mannich addition reaction allowed us to obtain enantiomerically pure (R)- or (S)-configured 3-amino-4,4,4-trifluorobutanoic acids after hydrolysis and decarboxylation of the corresponding β-aminomalonates.

ChemInform Abstract: Asymmetric Synthesis of α‐Amino Acids via Homologation of Ni(II) Complexes of Glycine Schiff Bases. Part 2. Aldol, Mannich Addition Reactions, Deracemization and (S) to (R) Interconversion of α‐Amino Acids

AbstractReview: 61 refs.

ChemInform Abstract: Synthesis of Fluorine‐Containing α‐Amino Acids in Enantiomerically Pure Form via Homologation of Ni(II) Complexes of Glycine and Alanine Schiff Bases

AbstractReview: 144 refs.

Asymmetric synthesis of α-amino acids via homologation of Ni(II) complexes of glycine Schiff bases. Part 2: Aldol, Mannich addition reactions, deracemization and (S) to (R) interconversion of α-amino acids

This review provides a comprehensive treatment of literature data dealing with asymmetric synthesis of α-amino-β-hydroxy and α,β-diamino acids via homologation of chiral Ni(II) complexes of glycine Schiff bases using aldol and Mannich-type reactions. These reactions proceed with synthetically useful chemical yields and thermodynamically controlled stereoselectivity and allow direct introduction of two stereogenic centers in a single operation with predictable stereochemical outcome. Furthermore, new application of Ni(II) complexes of α-amino acids Schiff bases for deracemization of racemic α-amino acids and (S) to (R) interconversion providing additional synthetic opportunities for preparation of enantiomerically pure α-amino acids, is also reviewed. Origin of observed diastereo-/enantioselectivity in the aldol, Mannich-type and deracemization reactions, generality and limitations of these methodologies are critically discussed.

ChemInform Abstract: Gold‐Catalyzed Mannich Addition Reactions of 1,3‐Dicarbonyl Compounds with N‐Protected Imines.

AbstractThis is the first gold‐catalyzed variant of this reaction.

Gold‐Catalyzed Mannich Addition Reactions of 1,3‐Dicarbonyl Compounds with N‐Protected Imines

AbstractThe first (N‐heterocyclic carbene)AuI‐catalyzed Mannich addition reactions of N‐protected imines with different 1,3‐dicarbonyl compounds are described. IPrAuNTf2 was proven to be an efficient catalyst for the reactions of β‐keto esters and 1,3‐diketones with N‐sulfonylimines to afford the desired β‐amino carbonyl compounds in good yields under very mild conditions.

Gold(I)-catalyzed diastereo- and enantioselective 1,3-dipolar cycloaddition and Mannich reactions of azlactones.

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions, respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold catalysts, namely C(2)-symmetric bis(phosphinegold(I) carboxylate) complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes and the chemistry of the resultant cycloadducts are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem mass spectrometry studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component.

Hydroalkylation leading to heterocyclic compounds (Part 2): practical synthesis of polysubstituted 1,2,3,4-tetrahydropyridines through multicomponent reactions (MCRs)

Polysubstituted 1,2,3,4-tetrahydropyridines were synthesized through hydroalkylation of electron-deficient alkynes, followed by double Mannich addition reactions, which is a practical protocol with atom efficiency and good substrate scope.

ChemInform Abstract: Direct Carbon—Carbon Bond Formation via Soft Enolization of Thioesters: An Operationally Simple Mannich Addition Reaction.

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Direct Carbon-Carbon Bond Formation via Soft Enolization of Thioesters: An Operationally Simple Mannich Addition Reaction

Thioesters undergo soft enolization and direct Mannich additionto sulfonylimines on treatment with magnesium bromide ethyl etherateand N, N-diisopropylethylamine.The reactions proceed readily with a range of sulfonylimines and,in the case of 2,4,6-triisopropylphenyl thiopropionate, give moderateto good SYN dia-stereoselectivity.

Stereocontrol in radical Mannich equivalents for aminosugar synthesis: haloacetal and 2-(phenylthio)vinyl tethered radical additions to α-hydroxyhydrazones

Studies of stereocontrol in two types of radical equivalents of Mannich addition reactions offer new insights for application to aminosugar synthesis. In the first method, haloacetal addition (Ueno–Stork reaction) is extended to dihydroxyhydrazones, leading to an adduct with the unexpected 3- epi- l-daunosamine configuration. A neighboring α-benzyloxy substituent causes a dramatic reversal of stereocontrol compared with hydrazones where this substituent is absent; vicinal dipole repulsion is proposed to account for the diastereoselectivity. In the second method, radical addition–cyclization with thiophenol and treatment with fluoride leads to diastereoselective group transfer from a silicon-tethered ethynyl group to the C N bond of hydrazones, affording anti-hydrazino alcohols with a trans-2-(phenylthio)vinyl substituent. The one-pot process occurs under neutral, tin-free radical conditions, and offers stereocontrol which is complementary to the haloacetal method. Synthetic utility of the radical Mannich concept is demonstrated in a brief asymmetric synthesis of N-trifluoroacetyl- l-daunosamine from achiral precursors.