Novel ionic liquid with both lewis and brønsted Acid sites for Michael addition

Ionic liquid with both Lewis and Brønsted acid sites has been synthesized and its catalytic activities for Michael addition were carefully studied. The novel ionic liquid was stable to water and could be used in aqueous solution. The molar ratio of the Lewis and Brønsted acid sites could be adjusted to match different reactions. The results showed that the novel ionic liquid was very efficient for Michael addition with good to excellent yields within several min. Operational simplicity, high stability to water and air, small amount used, low cost of the catalyst used, high yields, chemoselectivity, applicability to large-scale reactions and reusability are the key features of this methodology, which indicated that this novel ionic liquid also holds great potential for environmentally friendly processes.     

Hydroxyapatite: new efficient catalyst for the Michael addition

The synthetic hydroxyapatite is a new basic catalyst for Michael addition of mercaptans to chalcone derivatives with high yields in few minutes and mild reaction conditions. By-products of usual undesirable reactions in Michael addition such as 1.2-addition, bis-addition and polymerisation are not observed. The yields obtained are good to excellent.     

Using Conveniently Designed α‐Amino Ketones in Michael Reactions under Iminium Catalysis: Enantioselective Synthesis of γ‐Lactams and γ‐Amino‐δ‐keto Esters

The behaviour of aminoacetophenones as Michael donors in catalytic enantioselective Michael reactions with α,β‐unsaturated aldehydes under iminium activation has been studied. These compounds react with each other in the presence of catalytic amounts of a chiral secondary amine through a Michael/hemiaminal formation cascade process which proceeds with high yields and enantiocontrol. Elaboration of these adducts by oxidation allows the easy access to chiral disubstituted γ‐lactams and other synthetically useful chiral building blocks such as γ‐amino‐δ‐keto esters or β‐substituted δ‐oxoamides are accessible from the obtained adducts by simple transformations.     

Brønsted Base‐Catalyzed Tandem Isomerization–Michael Reactions of Alkynes: Synthesis of Oxacycles and Azacycles

An efficient synthesis of oxacycles and azacycles was developed using a Brønsted base‐catalyzed tandem alkyne isomerization–Michael reaction sequence. Functionalized 2‐alkylidenetetrahydrofurans were prepared by an intramolecular oxy‐Michael reaction on an allene that was generated in situ from an alkynoate. The aza‐Michael version using alkynylamines, alkynylamides and alkynyl carbamates led to piperidines, lactams and oxazolidinones, respectively. An enantioselective version of this reaction resulted in an axially chiral lactam with high enantioselectivity. Some alkynes, however, were unable to complete the intramolecular Michael reactions and provided enantioenriched allenes.     

Relationship between electron sensitivity and chemical structures of polymers as electron beam (EB) resists. V: Polyamides containing sulfur groups as positive eb resists

Polyamidethioethers were synthesized and evaluated as positive electron beam (EB) resists, The polyamidethioethers decomposed easily with EB exposure. At high doses (indicating low sensitivity), crosslinking reactions occurred for polyamidethioethers having C-S bonds produced by Michael addition, but the other polyamidethioethers did not crosslink. The C-S bonds produced by Michael addition may influence crosslinking rather than decomposition. The sensitivity of oxidized polyamidethioether was higher than that of the nonoxidized polymer with no change in resolution. The oxidized polyamidethioether had a high sensitivity and a high resolution, and is adaptable as a positive EB resist.     

Chiral Primary Amine Tagged to Ionic Group as Reusable Organocatalyst for Asymmetric Michael Reactions of C‐Nucleophiles with α,β‐Unsaturated Ketones

The first primary amine‐derived organocatalyst modified with an ionic group for asymmetric Michael reactions of C‐nucleophiles with α,β‐unsaturated ketones was synthesized. In the presence of this catalyst and an acidic co‐catalyst (AcOH), hydroxycoumarin and its sulfur‐containing analogue reacted with benzylideneacetone derivatives or cyclohexenone to afford the corresponding Michael adducts in high yields (up to 97%) and with reasonable enantioselectivity (up to 80%). The catalyst could be easily recovered and efficiently reused three times, afterwards, its activity and stereodifferentiating ability gradually declined. The analysis of recovered catalyst samples by ESI‐MS allowed us to detect undesirable side reactions that poisoned the catalyst, and propose an approach for its reactivation.     

手性伯胺催化剂催化Michael加成反应的研究进展

在许多不对称有机反应中,手性伯胺催化剂已被证实是一种高效的催化剂,被广泛应用于各种Michael加成反应中。Michel加成是有机合成中构建碳一碳键的重要反应之一,本文综述了近年来手性伯胺催化剂在Michael加成反应中的研究新进展。     

Development of cascade reactions for the concise construction of diverse heterocyclic architectures

Heterocyclic structural architectures occur in many bioactive natural products and synthetic drugs, and these structural units serve as important intermediates in organic synthesis. This Account documents our recent progress in the development of cascade reactions to construct complex carbocycles and heterocycles. We describe the rational design of cascade reactions and in-depth investigations of their mechanism as well as their applications in the synthesis of drugs, natural products, and related molecular analogs. Relying on knowledge about the dipole-type reactivity of sulfur ylides, we have developed three different types of cascade reactions: a [4 + 1] annulation/rearrangement cascade, a [4 + 1]/[3 + 2] cycloaddition cascade, and a Michael addition/N-alkylation cascade. Using these processes, we can generate oxazolidinones, fused heterocycles, and pyrrolines starting with simple and readily available substances such as nitroolefins and unsaturated imines. We have also developed corresponding enantioselective reactions, which are guided by axial chirality and asymmetric H-bonding control. In addition, by relying on the reactivity characteristics of newly designed acrylate-linked nitroolefins, we have disclosed an asymmetric Michael/Michael/retro-Michael addition cascade using the combination of a protected hydroxylamine and a bifunctional organocatalyst. Using this methodology, we prepared chiral chromenes in good yields and with high enantioselectivities. Moreover, a series of double Michael addition cascade reactions with anilines, thiophenols, and benzotriazoles generated highly functionalized chromanes. Via mechanistically distinct cascade processes that start with vinyl-linked indoles, we have synthesized polycyclic indoles. Intermolecular cross-metathesis/intramolecular Friedel-Crafts alkylation cascades, promoted by either a single ruthenium alkylidene catalyst or a sequence involving Grubbs' ruthenium catalyst and MacMillan's imidazolidinone catalyst, converted ω-indolyl alkenes into tetrahydrocarbazoles, tetrahydropyranoindoles, and tetrahydrocarbolines. In addition, we constructed tetrahydrocarbazoles and tetrahydroquinones using organocatalytic Friedel-Crafts alkylation/Michael addition cascades that used 2-vinyl indoles as common starting materials. Most green plants carry out photosynthesis to produce organic substances relying on readily available and renewable solar energy. In a related manner, we have also developed two cascade reactions that merge visible light-induced aerobic oxidation with either [3 + 2] cycloaddition/oxidative aromatization or intramolecular cyclization. These processes lead to the formation of pyrrolo[2,1-a]isoquinolines and enantiopure tetrahydroimidazoles, respectively.     

Highly Diastereo‐ and Enantioselective Catalytic Domino Thia‐Michael/Aldol Reactions: Synthesis of Benzothiopyrans with Three Contiguous Stereocenters

Highly enantioselective organocatalytic domino thia‐Michael/aldol reactions between 2‐mercaptoacetophenone and α,β‐unsaturated aldehydes are presented. The reactions proceed with excellent chemo‐, diastereo‐ and enantioselectivity to give the corresponding benzothiopyran derivatives in high yields with up to >15:1 dr and 96 to >99 % ee.     

Asymmetric domino Michael–aldol reactions catalyzed by recyclable PEG supported chiral primary aminoalcohol and primary–secondary diamine catalysts in water

PEG supported chiral primary aminoalcohol and primary–secondary diamine have been synthesized and used to catalyze the asymmetric domino Michael–aldol reactions of benzyl benzoylacetate and α,β-unsaturated ketones in water to afford optically active cyclohexanones. Excellent diastereoselectivities, good to excellent enantioselectivities and good yields were obtained, and catalyst recycling was accompanied by almost intact diastereo- and enantioselectivity and some loss of the chemical efficiency.     

(硫)脲催化剂催化杂原子Michael加成反应的研究进展

(硫)脲催化剂已被证实是一种高效的有机催化剂,被广泛应用于各种Michael加成反应中。关于C-C键生成的Michael加成反应的综述较多,但关于杂原子的Michael加成反应的文章较少。本论文简述了(硫)脲催化剂在杂原子Michael加成反应中的研究新进展。     

Thiol Michael addition reaction: a facile tool for introducing peptides into polymer‐based gene delivery systems

Polymers, as widely used non‐viral gene carriers, suffer from high cytotoxicity and relatively low transfection efficiency. Such crucial drawbacks of polymers could be solved by incorporating short and bioactive peptides. The resulting synthetic polymer–peptide conjugates can not only maintain their own special characteristics, but also gain novel characteristics far beyond those of their parent polymer and peptide components to overcome barriers to gene delivery. There are various chemoselective reactions applied in the synthesis of polymer–peptide conjugates, such as Heck, Sonogashira and Suzuki coupling, Diels–Alder cycloaddition, click chemistry, Staudinger ligation, reductive alkylation and oxime/hydrazone chemistry. Among them, thiol–ene click reactions, including thiol–ene radical and thiol Michael addition reactions, are common methods for preparing peptide–polymer conjugates. In this review, we focus on thiol Michael addition reactions, elaborate on their mechanisms and highlight their applications in the synthesis of polymer–peptide conjugates for gene delivery. © 2017 Society of Chemical Industry     

A Highly Enantioselective Catalytic Domino Aza‐Michael/Aldol Reaction: One‐Pot Organocatalytic Asymmetric Synthesis of 1,2‐Dihydroquinolidines

The highly enantioselective organocatalytic domino aza‐Michael/aldol reaction is presented. The unprecedented, chiral amine‐catalyzed asymmetric domino reactions between 2‐aminobenzaldehydes and α,β‐unsaturated aldehydes proceed with excellent chemo‐ and enantioselectivity to give the corresponding pharmaceutically valuable 1,2‐dihydroquinolines derivatives in high yields with 90 to >99 % ee.     

β-酮酸酯类化合物与丁烯酮的Micheal加成反应研究

2-氧代环戊烷甲酸甲酯或2-氧代环己烷甲酸甲酯与短链α,β-不饱和羰基化合物丁烯酮在六水合三氯化铁催化、无溶剂条件下进行Michael加成反应,能有效避免副反应的发生。该方法也可应用于其他β-酮酸酯类化合物,反应简便易行,收率高。所得到化合物结构均经1H-NMR和MS谱确证。     

Synthesis of an Aza Chiral Crown Ether Grafted to Nanofibrous Silica Support and Application in Asymmetric Michael Addition

We report on the synthesis of a new, supported phase transfer catalyst and its asymmetric induction. An inorganic-polymer-supported chiral crown ether was prepared by the reaction between an optically active macrocycle deriving from methyl-α-d-glucopyranoside and silica nanofibres. The inorganic carrier of the catalyst has high specific surface area due to its nanofibrous structure, which is favourable for heterogeneous catalytic reactions. SiO₂ fibres were electrospun from silica sol which was prepared via sol–gel reactions from tetraethylorthosilicate. The asymmetric Michael reaction of diethyl acetamidomalonate and β-nitrostyrene was selected for the comparison of the performance of various glucopyranoside-based macrocycles. The asymmetric inductions of macrocycles provided 20–99 % enantiomeric excess. A triethoxysilyl derivative was prepared from the highly enantioselective macrocycle in order to immobilize it on the surface of the silica nanofibres. The supported glucose based monoaza-15-crown-5 type macrocycle was characterized by X-ray photoelectron spectroscopy and compared with non-supported native crown ethers in the asymmetric Michael addition. The immobilized phase-transfer catalyst generated high enantiomeric excess (82 %) in spite of the fact that it was used in a three-phase reaction.     

Some Iron(III) Catalyzed Michael Reactions of Chiral Donors,bis‐Donors,and a bis‐Acceptor

Michael reactions of β‐keto esters 1a—1h with methyl vinyl ketone ( 2a ) catalyzed by FeCl₃ · 6 H₂O (5 mol%) proceed with up to 99% yield. Conversion of β‐keto esters 1a—1e derived from chiral alcohols with 2a result in only very low diastereoselectivities (max. de 20%). A bis‐β‐keto ester 1i and a bis‐vinyl ketone 2b — both valuable monomers for poly‐Michael reactions — are synthesized from common starting materials in up to gram quantities.     

Base Catalysis in the Synthesis of Fine Chemicals

The catalytic properties of hydrotalcites are investigated for reactions of aldolisation, Meerwein–Ponndorf–Verley hydrogenations, epoxidations and oxidations, Michael and Wadsworth–Emmons additions. Excellent yields have been reported using mild conditions and catalysts which can be easily separated from the reaction medium and could be regenerated. The catalytic properties are controlled by the activation of the solid, and traces of chlorine appear to be deleterious. In many cases rehydration increases activity dramatically. Solid bases give a very specific catalysis for instance with Michael or Wadsworth–Emmons reactions of aldolisable compounds due to the exclusion of carbonyls from the surface by the other reactant.     

Curing,compatibility, and fracture toughness for blends of bismaleimide and a tetrafunctional epoxy resin

The curing, compatibility, and fracture toughness of blends of 4,4 ′-bismaleimidodiphenylmethane (BDM)/tetraglycidyl diamino-diphenyl methane (TGDDM) were investigated. Diamino-diphenyl sulfone (DDS) was used as a curing agent. BDM alone could be both homopolymerized (at a lower temperature) and could also undergo Michael addition reactions with the primary amine of DDS. The secondary amine of DDS did not react with BDM. However, the network produced by homopolymerization was not miscible with that produced by the latter reactions. Curing of TGDDM with DDS took place almost at the same temperature as that of the homopolymerization of BDM, but well below the temperature of the Michael addition reaction. When a BDM/TGDDM mixture was cured with DDS in the stoichiometric ratio, the miscibility of the cured system increased with the amount of TGDDM. This was attributed to the fact that the network produced by Michael addition reactions was diminished. When DDS reacted entirely with TGDDM, the BDM/TGDDM/DDS cure yielded only a TGDDM/DDS network and a BDM homopolymerized network, which were not only miscible, but are also interpenetrating. The superior interpenetrated network, as indicated by the highest fracture toughness, was found at BDM/TGDDM = 40/60 weight ratio in the BDM/TGDDM/DDS curing systems.     

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

The highly diastereo‐ and enantioselective relay cascade Michael/Michael/Henry reaction catalyzed by combination of readily available diphenylprolinol silyl ether and the quinine thiourea in a one‐pot fashion has been developed. Up to 70% yield and up to >99% enantioselectivity of the single major isomer were obtained from the cascade reactions.     

5-咪唑甲基-二氢吡咯-3-甲酸甲酯的合成

以组氨酸为原料,经选择性咪唑环氮的保护、氨基迈克尔加成、甲基化、关环、还原和消除等反应合成了标题化合物.对其中关键步骤氨基迈克尔加成反应和分子内关环反应进行了研究,获得了较优的工艺条件:在迈克尔加成反应中以甲醇钠为碱,甲醇为溶剂;在分子内环化反应中选择以叔丁醇钾为碱,四氢呋喃为溶剂.目标产物的总收率为28.3％,结构经1HNMR和MS进行了确证.