Synthesis of new polyfunctional 2-pyrrolidinones from methyl 2-(carboethoxyhydroxymethyl)acrylate

The synthesis of new polyfunctional 2-pyrrolidinone derivatives from methyl 2-(carboethoxyhydroxymethyl)acrylate is described. These alkenes present an extremely high reactivity upon Michael addition with primary amines leading to a simple, mild, and efficient route to the preparation of new polyfunctional pyrrolidinones.     

Highly Enantioselective Aza‐Michael Reaction between Alkyl Amines and β‐Trifluoromethyl β‐Aryl Nitroolefins

The aza‐Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza‐Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N‐heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza‐Michael reaction between primary alkyl amines and β‐trifluoromethyl β‐aryl nitroolefins. In contrast to classical conjugate‐addition reactions, a strategy of HOMO‐raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99 %) with excellent enantioselectivity (up to 98 % ee).     

Synthesis of the Stereoisomers of the Sex Pheromones of the Southern Corn Rootworm

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Asymmetric Michael addition of malonates to enones catalyzed by a primary β-amino acid and its lithium salt

Highly enantioselective Michael addition of malonates to enones was achieved using a mixed catalyst consisting of a primary β-amino acid, O-TBDPS (S)-β-homoserine, and its lithium salt. Various cyclic and acyclic enones were converted into 1,5-ketoesters in high yields (up to 92%) with high enantioselectivity (up to 97% ee) under mild reaction conditions. Details of synthesis of the catalyst, optimization of the reaction conditions for the Michael addition reaction, and a plausible reaction mechanism are described.     

Iron-catalyzed Michael reactions revisited: a synthetically useful process for the preparation of tri-carbonyl compounds and chiral warfarin

The LBAs (Lewis acid-assisted Brønsted acid catalysis) is proposed as possible mechanistic process in the simple FeCl₃-catalyzed Michael reactions of chalcones with active methylene compounds in organic solvents. And iron salts were found to be effective promoters in the asymmetric Michael addition of 4-hydroxycoumarin to α,β-unsaturated ketone, which resulted in excellent yield and high level of enantioselectivity (up to 91% ee) in the presence of low catalytic amount of iron and simple chiral primary amine.     

New poly(ester amide)s from alkyl 2‐(carboethoxyhydroxymethyl)acrylates

The synthesis of alkyl 2‐(carboethoxyhydroxymethyl)acrylates via the Bayllis‐Hillmann reaction pathway is described. These compounds are found to be poor monomers when involved in free radical polymerizations but present an extremely high reactivity upon Michael addition with primary amines leading to a simple, mild and efficient route to the preparation of new multifunctional heterocycles and polymers with potential applications in biodegradable coatings. Real‐time NMR spectroscopy permitted monitoring the extent of the reaction sequence and determining the conversion profile of reactants and Michael adduct intermediate. Poly(ester amide)s derived from diamine and hexane bis‐2‐(carboethoxyhydroxymethyl)acrylate were synthesized at room temperature by means of a very efficient Michael addition/cyclization polymerization. These polymers display excellent adhesion to metal, glass, and paper substrates and interesting hydrolytic susceptibility. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3182–3192, 2008     

A simple and efficient synthesis of (±)-mesembrine

A simple and efficient synthesis of (±)-mesembrine 1 is described employing double Michael addition and as the key step in 18% overall yield.     

Organocatalytic highly enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes

The first organocatalytic enantioselective Michael addition of 2-hydroxy-1,4-naphthoquinones to nitroalkenes for the direct synthesis of chiral nitroalkylated naphthoquinone derivatives was investigated. Good yields and excellent enantioselectivities (up to >99% ee) could be achieved. This organocatalytic asymmetric Michael addition provides an efficient route toward the synthesis of optically active functionalized naphthoquinones.     

Aqueous‐mediated Michael Addition of Active Methylene Compounds with Nitroalkenes

A simple, atom economical and highly efficient green protocol has been developed for the synthesis of Michael adducts of nitroalkenes and 2‐amino‐2‐chromene derivatives by Michael addition of active methylene compounds (such as malononitrile and ethyl cyanoacetate) to nitroalkenes under aqueous‐mediated conditions. This green approach provided the desired products in high yields and the reaction scope proved to be quite broad.     

Simple synthesis of 1,3-cyclopentanedione derived probes for labeling sulfenic acid proteins

Facile, two-step synthesis and kinetic characterization of new chemical probes for selective labeling of sulfenic acid (-SOH) in proteins are presented. The synthesis route relies on the simple and highly efficient Michael addition of thiol containing tags or linkers to 4-cyclopentene-1,3-dione, the unsaturated derivative of 1,3-cyclopentanedione.     

Enantioselective synthesis of trans-dihydrobenzofurans via primary amine-thiourea organocatalyzed intramolecular Michael addition

A primary amine-thiourea organocatalyzed intramolecular Michael addition access was developed for the synthesis of trans-dihydrobenzofurans. Under the catalysis of an (R,R)-1,2-diphenylethylamine derived primary amine-thiourea bearing a glucosyl scaffold, the corresponding trans-dihydrobenzofurans were obtained in high yields with excellent level of enantioselectivities (94 to >99% ee). Moreover, an in situ isomerization occurring at high temperature gave good to excellent trans/cis ratios as well (trans/cis: 84/16-96/4).     

Iron-mediated one-pot formal nitrocyclization onto unactivated alkenes

One-pot synthesis of heterocycles having a nitromethyl group was achieved by sequential steps that involved chloronitration of alkenes using iron(III) nitrate nonahydrate followed by elimination and intramolecular Michael addition. This reaction provides an efficient method for the synthesis of heterocycles due to the simple experimental procedure and the use of inexpensive reagents of low toxicity.     

KOtBu‐Catalyzed Michael Addition Reactions Under Mild and Solvent‐Free Conditions

Designed transition metal complexes predominantly catalyze Michael addition reactions. Inorganic and organic base‐catalyzed Michael addition reactions have been reported. However, known base‐catalyzed reactions suffer from the requirement of solvents, additives, high pressure and also side‐reactions. Herein, we demonstrate a mild and environmentally friendly strategy of readily available KO^tBu‐catalyzed Michael addition reactions. This simple inorganic base efficiently catalyzes the Michael addition of underexplored acrylonitriles, esters and amides with (oxa‐, aza‐, and thia‐) heteroatom nucleophiles. This catalytic process proceeds under solvent‐free conditions and at room temperature. Notably, this protocol offers an easy operational procedure, broad substrate scope with excellent selectivity, reaction scalability and excellent TON (>9900). Preliminary mechanistic studies revealed that the reaction follows an ionic mechanism. Formal synthesis of promazine is demonstrated using this catalytic protocol.     

Noyori’s Ts-DPEN ligand: an efficient bifunctional primary amine-based organocatalyst in enantio- and diastereoselective Michael addition of 1,3-dicarbonyl indane compounds to nitroolefins

Noyori’s Ts-DPEN ligand bearing an amino sulfonamide moiety and with a primary amino group on a chiral scaffold was found to be a simple and efficient bifunctional organocatalyst for the asymmetric Michael addition of 1,3-dicarbonyl compounds to nitroolefins, which gave highly functional Michael adduct with quaternary stereocenters in good enantioselectivities (up to 84%ee) and dr (up to 5.7:1 dr).     

An efficient and clean Michael addition of indoles to electron‐deficient olefins under solvent‐ and catalyst‐free condition

An efficient Michael addition of indoles to electron‐deficient olefins under solvent‐ and catalyst‐free condition afforded biologically important 3‐substituted indole derivatives in good to excellent yields was reported. The acidic N? H proton of indole plays a key role in Michael addition of indoles to electron‐deficient olefins. This very simple procedure provides an efficient and clean process for the synthesis of indole derivatives. J. Heterocyclic Chem., (2011).     

Highly enantioselective Michael addition of aromatic ketones to nitroolefins promoted by chiral bifunctional primary amine-thiourea catalysts based on saccharides

[reaction: see text] A new class of thiourea catalysts have been developed which integrate saccharide and primary amine moieties into one small organic molecule. These simple catalysts are shown to be highly enantioselective for direct Michael addition of aromatic ketones to a range of nitroolefins (up to 98% ee).     

Environmental Friendly Synthesis of Novel Isatin Ketal and Isatin Schiff Base Derivatives Using Michael Addition Reaction under Solvent‐Free Conditions

An efficient and simple procedure for the synthesis of novel isatin derivatives is described. Michael addition of aniline Schiff bases of isatin or p‐toluidine Schiff bases of isatin to fumaric esters affords the Michael adduct compounds in good to high yields in the presence of K₂CO₃ and tetrabutylammonium bromide (TBAB) under solvent‐free conditions. Repeating of this reaction about spiro[1,3‐dioxolane‐2,3′‐indol]‐2′(1′H)‐one, as a Michael donor, in the presence of 1,4‐diazabicyclo[2.2.2]octane (DABCO) gives Michael adducts in remarkable yields under the same conditions.     

Calixarene-based highly efficient primary amine–thiourea organocatalysts for asymmetric Michael addition of aldehydes to nitrostyrenes

The synthesis of calix[4]arene-based chiral bifunctional primary amine–thiourea catalysts has been described from p-tert-butylcalix[4]arene for the first time. The calix[4]arene-based catalysts were successfully applied to promote Michael addition of aldehydes with nitroalkenes affording preferentially the (R)- or (S)-adducts in high yields (up to 95%) and excellent enantioselectivities (up to 99% ees).     

Synthesis of novel functional polycyclic chromones through Michael addition and double cyclizations

A base-promoted, microwave-assisted one-pot tandem reaction from simple 3-(1-alkynyl)chromones with 2-halobenzylic nitriles (esters or amides) for the synthesis of novel functional polycyclic chromenones has been developed. This tandem process involves multiple reactions, such as Michael addition and double cyclizations without a transition metal catalyst.     

An oxidative coupling for the synthesis of arylated quaternary stereocentres and its application in the total synthesis of powelline and buphanidrine

Catechol derivatives directly bonded to all-carbon quaternary stereocentres are prevalent in nature. An oxidative coupling strategy for the synthesis of this motif is described. Pivoting on the base-catalysed Michael addition of carbon-centred pro-nucleophiles to in situ generated ortho-benzoquinones, the method is broad in scope, high yielding and provides remarkably simple access to this challenging motif. The application of this methodology in the total synthesis of the crinane-type amaryllidaceae alkaloids (±)-powelline and (±)-buphanidrine is demonstrated and our efforts towards an enantioselective synthesis described.