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An efficient N-heterocyclic carbene (NHC)-catalyzed asymmetric conjugate addition reaction to afford synthetically challenging benzofuranone derivatives having vicinal all-carbon quaternary and tertiary stereocenters is presented. The reaction operates solely through noncovalent interaction between a newly designed NHC and the substrates, providing access to a series of functionalized benzofuranones in good yields and with high ee values. The protocol applies to preparative-scale synthesis. A catalytic cycle involving a noncovalent substrate–NHC interaction is implicated in the process, based on a mechanistic control study. [ABSTRACT FROM AUTHOR]

Epilepsy, a predominant neurological disorder affecting about 1% of the worldwide population, demands effective treatment options. An antiepileptic drug called brivaracetam has proven amazing efficacy in preventing epilepsy progression, garnering attention for novel synthesis methods. Despite recent progress in conventional synthesis routes, challenges such as expensive catalysts, inconvenient substrates, and hazardous solvents persist. In this context, we share the first finding that immobilized penicillin G acylase (IPGA) can catalyze the polarity reversal conjugate addition reaction. This synthesis is straightforward and does not require any purification. Yield up to 92.41% was achieved at 55 °C using dimethyl sulfoxide as a solvent. The catalytic specificity of IPGA was demonstrated through control experiments. Nonetheless, this research demonstrates the potential of IPGA and other biocatalysts to enable sustainable and effective organic synthesis processes and showcase the promiscuity of existing enzymes. [ABSTRACT FROM AUTHOR]

We rationally designed and successfully developed novel dipeptidic proline amide–isothiouronium catalysts for asymmetric conjugate addition reactions between various aldehydes and nitroolefins, which generated 1,4‐addition products with up to 95% yields, 92:8 syn‐diastereoselectivity, and 96% enantiomeric excess. The catalysts, which were prepared via simple methylation of the corresponding thiourea, can provide the desired enantiomeric syn‐1,4‐adducts by exchanging the configuration of the N‐terminal proline moiety. [ABSTRACT FROM AUTHOR]

In the present study we have disclosed here that ZnO nanorod (ZnO‐NR) can effectively be used as a catalyst for various C−C bond formation reactions, i. e. allylation, as well as one‐pot three components conjugate addition and Knoevenagel‐allylation of isatins. The corresponding products were obtained with good to excellent yields under solvent‐free conditions in most cases at RT. The catalyst was successfully recycled for up to five cycles for allylation reaction and one pot three components Knoevenagel‐allylation reaction of isatin. X‐ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used to characterize the structure and morphology of the catalyst. [ABSTRACT FROM AUTHOR]

This article explores the advancements in stereodivergent carbon-carbon bond-forming reactions in organic chemistry. These reactions allow for the control of multiple stereogenic centers in a reaction, providing synthetic chemists with more flexibility and efficiency in constructing complex molecular structures. The article emphasizes the importance of these methods in drug discovery, where different stereoisomers of a drug can have different biological activities. The field of stereodivergent catalysis has grown significantly, with mono-catalytic and bifunctional catalytic methods contributing to the development of these reactions. Dual catalysis faces challenges, but progress has been made in finding compatible reaction types. The ultimate challenge lies in achieving high yields of multiple stereoisomers, but advancements in high-throughput experimentation and catalyst optimization may help overcome this challenge. [Extracted from the article]

DESs were profitably investigated as solvents and promoters of the conjugate reaction addition of cyclic and acyclic α‐nitroketones to a variety of electron‐poor alkenes. The best results were obtained conducing the reaction in betaine:1,2‐propanediol (1 : 5 molar ratio) DES at room temperature, and enones were demonstrated to be the most effective Michael acceptors. The same reaction conducted by using different molar ratios of the components in this DES showed the eutectic point to be the most effective in terms of the yields observed. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of aryl-C-glycosides, specifically focusing on 2-deoxy-aryl-C-glycosides, which have potential biological activities. The authors present a new method using palladium catalysts for the synthesis of these compounds through 1,4-conjugate addition reactions. They conducted an optimization study to determine the best reaction conditions and found that palladium acetate and acetic acid were effective additives. The article also provides detailed information on the preparation and characterization of several compounds, including their chemical structures and physical properties. This information can be valuable for researchers studying these compounds or related chemical reactions. [Extracted from the article]

A three‐component phase‐transfer catalytic domino reaction involving cyclohexane‐1,3‐dione‐derived enaminones, 5‐alkenyl rhodanines, and haloalkanes has been developed. This protocol produces a wide range of 3‐thioquinoline‐2,5‐diones in yields of 52–81%. The construction of a C−S bond at the C‐3 position of the quinoline‐2,5‐dione framework expands its structural diversity. Studies into the reaction mechanism revealed that the reaction undergoes a conjugate addition, ammonolysis, elimination, and nucleophilic substitution sequence. The synthetic potential of the reaction was demonstrated by the gram‐scale syntheses of representative products. Chloroalkyl chains were installed on the sulfur atoms of most products obtained in this reaction. Diversified product derivatives were obtained by exploiting the favorable leaving nature of the chloride moiety. [ABSTRACT FROM AUTHOR]

Activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by Kelch-like ECH-associated protein 1 (Keap1) alkylation plays a central role in anti-inflammatory therapy. However, activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified. Deoxynyboquinone (DNQ) is a natural small molecule discovered from marine actinomycetes. The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1. DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo. The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be the α, β-unsaturated amides moieties by a chemical reaction between DNQ and N -acetylcysteine. DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway. Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation. The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry. DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489 (Cys489) on Keap1-Kelch domain, ultimately enabling the activation of Nrf2. Our findings revealed that DNQ exhibited potent anti-inflammatory capacity through α, β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain, suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies. [Display omitted] • Small molecule DNQ exhibits potent anti-inflammatory effects via activation of Nrf2. • Target of DNQ was elucidated with a synthesized probe combined with Click Chemistry. • DNQ activates Nrf2 through alkylation and ubiquitination of Keap1-Kelch domain. • DNQ loses the anti-inflammatory capacity when site mutation of Keap1 at Cys489. [ABSTRACT FROM AUTHOR]

A regio‐ and diastereoselective conjugate addition reaction of Grignard reagents to fluoroalkyl α,β‐unsaturated N‐tert‐butanesulfinyl ketimines was disclosed. A range of different fluoroalkyls and Grignard reagents were well tolerated, giving up to 99% diastereomeric and regioisomeric ratios. This reaction provided a straightforward method for the synthesis of a variety of enantiomerically enriched α‐fluorinated enamines and derivatives which are difficult to achieve with other methods. [ABSTRACT FROM AUTHOR]

A novel, efficient and pragmatic method to prepare gem-diboron products with vicinal tertiary/quaternary stereocenters using LiTMP-mediated 1,6-conjugate addition of gem-diborylalkanes to para-quinone methides was described for the first time. The results showed that various gem-diboron products with vicinal tertiary and quaternary stereocenters could be formed within 15 min at ambient temperature. This simple protocol has also been applied for the efficient synthesis of the analogue of Bedaquiline. [ABSTRACT FROM AUTHOR]

The limited nucleophilic character and the bidentate nature of unactivated nitroalkane anions (nitronates) makes the corresponding alkylation and allylation procedures rather troublesome. This aspect is in sharp contrast with other commonly employed processes involving nitronate anions such as conjugate additions or nitroaldol reactions. This review summarizes the most rewarding approaches that along the years have been devised to overcome this limitation. Efficient methods are nowadays mainly based on metal‐catalyzed processes involving purely ionic or mixed ionic‐radical intermediates including photoenzymatic reactions. [ABSTRACT FROM AUTHOR]

This article discusses the use of nickelacycles as catalysts in the conjugate addition of organoboron compounds to ¿,ß-unsaturated ketones. The authors synthesized two different nickelacycles and evaluated their catalytic activity in this reaction. They found that the nickelacycles showed higher activity compared to corresponding palladacycles. The study provides insights into the deactivation pathways of the catalyst and compares the catalytic activity of nickelacycles with other catalysts. Overall, the research demonstrates the potential of nickelacycles as catalysts in carbon-carbon bond formation reactions. [Extracted from the article]

HRMS: I m i / I z i [M + NH SB 4 sb ] SP + sp calcd for C SB 14 sb H SB 15 sb ClFN SB 2 sb O SB 4 sb S SP + sp : 361.0420; found: 361.0416. HRMS: I m i / I z i [M + NH SB 4 sb ] SP + sp calcd for C SB 15 sb H SB 15 sb FN SB 3 sb O SB 4 sb S SP + sp : 352.0762; found: 352.0759. HRMS: I m i / I z i [M + NH SB 4 sb ] SP + sp calcd for C SB 15 sb H SB 15 sb FN SB 3 sb O SB 4 sb S SP + sp : 352.0762; found: 352.0765. HRMS: I m i / I z i [M + NH SB 4 sb ] SP + sp calcd for C SB 11 sb H SB 12 sb FN SB 2 sb O SB 4 sb S SB 2 sb SP + sp : 319.0217; found: 319.0221. [Extracted from the article]

Applications of photochemistry are becoming very popular in modern‐day life due to its operational simplicity, environmentally friendly and economically sustainable nature in comparison to thermochemistry. In particular photoinduced radical polymerisation (PRP) reactions are finding more biological applications and especially in the areas of dental restoration processes, tissue engineering and artificial bone generation. A type‐II photoinitiator and co‐initiator‐promoted PRP turned out to be a cost‐effective protocol, and herein we report the design and synthesis of a new efficient co‐initiator for a PRP reaction via a barrierless sequential conjugate addition reaction. Experimental mechanistic observations have been further complemented by computational data. Time for newly synthesised 1,2‐benzenedithiol (DTH) based co‐initiator promoted polymerisation of urethane dimethacrylate (UDMA, 70 %) and triethylene glycol dimethacrylate (TEGDMA, 30 %) in presence of 450 nm LED (15 W) under the aerobic conditions is 38 seconds. Polymeric material has high glass transition temperature, improved mechanical strength (860 BHN) and longer in‐depth polymerisation (3 cm). [ABSTRACT FROM AUTHOR]

The electronic effects of the bidentate ligands play a vital role in the transition metal‐catalyzed conjugate addition reactions. Here, the insertion step (rate‐determining step (RDS) of the conjugate addition) catalyzed by Pd(II)/Rh(I)‐complexes with 26 bipyridine‐type (bpy) ligands linking different substituent groups in the opposite sides (C4, C4′ position) are systematically studied by density functional theory (DFT). It is found that for both Pd(II)‐ and Rh(I)‐catalysis, the stronger the electron‐withdrawing group connecting to both C4 and C4′ positions of bpy ligands can promote the insertion step. The predominance of π‐back donation in Rh(I) and σ‐donation in Pd(II) is the main reason for above different electronic properties of Pd(II) and Rh(I)‐catalysis. This work gives enough theoretical guide to the rational design of the efficient transition metal‐based catalyst for conjugate addition. [ABSTRACT FROM AUTHOR]

The inherent ability of bio‐inspired underwater superoleophobicity to prevent oil/oily fouling underwater makes it appropriate for a wide range of applications related to environmental remediation, bio‐adhesion, microfluidics, chemical sensing, etc.; however, the co‐association of mechanical durability and optical transparency is essential for realistic performance. While the design of mechanically durable and absolutely optically transparent underwater superoleophobic coating remains challenging, here, a covalently cross‐linked and chemically reactive sol‐gel conversion process is introduced through 1,4‐conjugate addition reaction to achieve a substrate‐independent and tolerant coating for orthogonally modulating the underwater oil wettability, optical transparency, and even mechanical properties of highly deformable porous and fibrous substrates. The post‐modification of residual chemical reactivity in the prepared coating allows to embed underwater superoleophobicity, and the β‐amino‐ester‐cross‐links improve the mechanical property of selected deformable substrates. Moreover, it displayed unperturbed performance even after prolonged (30 days) exposures in practically relevant chemically harsh aquatic conditions—including extremes of pH, artificial seawater, surfactant contaminated water, etc. The approach is successfully applied to coat various substrates—including porous, fibrous, and planar objects, and it would be useful in protecting various relevant marine infrastructures from oil/oily fouling, and various other potential applications. [ABSTRACT FROM AUTHOR]

Regio- and stereoselective switchable synthesis of (E)- and (Z)-N-carbonylvinylated pyrazoles is first developed by using the Michael addition reaction of pyrazoles and conjugated carbonyl alkynes. Ag2CO3 plays a key role in the switchable synthesis of (E)- and (Z)-N-carbonylvinylated pyrazoles. Ag2CO3-free reactions lead to thermodynamically stable (E)-N-carbonylvinylated pyrazoles in excellent yields whereas reactions with Ag2CO3 give (Z)-N-carbonylvinylated pyrazoles in good yields. It is noteworthy that (E)- or (Z)-N1-carbonylvinylated pyrazoles are obtained with high regioselectivity when asymmetrically substituted pyrazoles react with conjugated carbonyl alkynes. The method can also extend to the gram scale. A plausible mechanism is proposed on the basis of the detailed studies, wherein Ag+ acts as coordination guidance. [ABSTRACT FROM AUTHOR]

Non‐sticking droplets wrapped with fine hydrophobic particles, namely liquid marbles, can be transported both on solid and water pool without an undesired spill of the inner encapsulated liquid. While the stimuli‐responsive release of the inner liquid in the target area is proposed, the time‐programmed release is not yet achieved. Herein, the hydrophobicity of nanoclay is modulated via a catalyst‐free 1,4‐conjugate addition reaction to form liquid marbles. This nanoclay liquid marble is robust and stable in air but collapses on the liquid pool with a specific lifetime. The lifetime of the liquid marble can be modulated over seconds to hours scale depending on the selection of chemically modulated wettability of the nanoclay. The critical mechanism of lifetime modulation is responsible for controlling the coalescence kinetics between the water pool and inner liquid by nanoclays' high diffusion length and chemically varied water spreading potential. The NC liquid marble's programmable lifetime to 'time‐bomb' type drug release and cascade chemical reaction is applied—without requiring any external intervention. [ABSTRACT FROM AUTHOR]

Most chiral secondary amine catalysts are usually synthesized from chiral amino acids and their derivatives. On the other hand, amine catalysts based on a binaphthyl backbone have previously been developed, and show unique chemo- and stereoselectivity in several asymmetric reactions. However, in spite of their utility, the applications of binaphthyl-based amines in asymmetric reactions are still rare due to their synthetic inefficiency. In this context, we have designed amine catalysts possessing a phenylcyclopropane scaffold as a novel chiral motif. These novel catalysts can be synthesized easily and construct a similar chiral environment to that of binaphthyl-based amine catalysts. In addition, a phenylcyclopropane-based amino sulfonamide is found to be an effective catalyst for syn -selective Mannich reactions and conjugate additions using alkynyl Z -ketimines. 1 Introduction 2 Design and Synthesis of Novel Chiral Secondary Amine Catalysts 3 Performance Evaluation of Phenylcyclopropane-Based Amine Catalysts 4 Development of Asymmetric Reactions Catalyzed by a Novel Chiral Amino Sulfonamide 5 Conclusions [ABSTRACT FROM AUTHOR]

The growing importance of structurally diverse and functionalized enantiomerically pure unnatural amino acids in the design of drugs, including peptides, has stimulated the development of new synthetic methods. This study reports the challenging direct asymmetric alkylation of cyclic ketones with dehydroalanine derivatives via a conjugate addition reaction for the synthesis of enantiopure ketone‐based α‐unnatural amino acids. The key to success was the design of a bifunctional primary amine‐thiourea catalyst that combines H‐bond‐directing activation and enamine catalysis. The simultaneous dual activation of the two relatively unreactive partners, confirmed by mass spectrometry studies, results in high reactivity while securing high levels of stereocontrol. A broad substrate scope is accompanied by versatile downstream chemical modifications. The mild reaction conditions and consistently excellent enantioselectivities (>95 % ee in most cases) render this protocol highly practical for the rapid construction of valuable noncanonical enantiopure α‐amino‐acid building blocks. [ABSTRACT FROM AUTHOR]

Covalent organic frameworks (COFs) having high specific surface area, tunable pore size and high crystallinity are mostly post modified following fluorine‐based and complex synthetic approaches to achieve a bio‐inspired liquid wettability, i.e. superhydrophobicity. Herein, a facile, non‐fluorinated and robust chemical approach is introduced for tailoring the water wettability of a new COF—which was prepared through Schiff‐base condensation reaction. A silane precursor was readily reacted with selected alkyl acrylates through 1,4‐conjugate addition reaction, prior to grafting on the prepared C4‐COF for tailoring different water wettability—including robust superhydrophobicity. The superhydrophobic C4‐COF (SH‐C4‐COF) that displayed significantly enhanced (>5 times; from 220 wt. % to 1156 wt. %) oil‐absorption capacity, was extended to address the relevant challenges of "oil‐in‐water" emulsion separation, rapidly (<1 minute) and repetitively (50 times) at diverse and harsh conditions. [ABSTRACT FROM AUTHOR]

Cysteine (Cys), a small-molecule biothiol, has recently been identified as a novel Glioblastoma (GBM) biomarker. The highly selective real-time monitoring and fluorescence imaging of Cys levels in vivo is of great significance for the early diagnosis and treatment of GBM. In this work, we reported a highly selective Cys fluorescent probe ZS-C1, based on quinoline according to the mechanism of the conjugate addition cyclization reaction. The Limit of Detection (LOD) of probe ZS-C1 was 1.97 μM, λex = 380 nm; λem = 531 nm. In vitro experiments showed that ZS-C1 could be distinguished from Hcy and GSH significantly, and the fluorescence quantum yield was reduced by 30 times. Further, biological imaging and 3D tumor sphere penetration assay showed that the ZS-C1 could monitor both exogenous and endogenous Cys in the living U87MG cells, and the fluorescence of probe ZS-C1 diffusely distributed inside the U87MG three-dimensional solid cell spheroid (up to 60 μM deep into the solid tumors). This work provided a potential tool for further investigations of Cys in biological samples and critical information for early diagnosis of glioma and guidance for clinical surgery. [ABSTRACT FROM AUTHOR]

N‐heterocyclic moieties are abundant among pharmaceuticals and agrochemicals, but a challenge for metalorganic and organocatalytic transformations. We present tripeptides of the type H‐Pro‐Pro‐Xaa as catalysts for stereoselective conjugate addition reactions between N‐heterocyclic substituted aldehydes and electrophiles. Alkyl substituents at the N‐terminal proline, the reactive site, were crucial for high chemo‐ and stereoselectivity. Different N‐heterocyclic moieties, even at both reaction partners, were readily tolerated and products were obtained in yields of 61–95% and enantioselectivities of up to 98% ee. [ABSTRACT FROM AUTHOR]

The article discusses the results of a study which developed an efficient asymmetric synthesis of triarylmethanes and diarylmethanes bearing a quaternary stereogenic center, through asymmetric multifunctionalization of simple alkynes via photo-irradiated organocatalysis. Topics include the general procedure for the asymmetric multifunctionalization of alkynes, the materials and methods and the considerations in devising a general strategy for the asymmetric multifunctionalization of alkynes.

Cyclopropane structure has been the object of interest in multiple investigations due to its prevalence in different natural products. In addition, this structure has a particular reactivity, specifically the 1,1‐cyclopropanedicarboxylate compounds, which act as acceptor‐donor cyclopropanes. Its reactivity could be compared with that of an α,β‐unsaturated carbonyl, which undergoes conjugate addition reaction and depending on the nature of the nucleophile this can lead to a cycloaddition reaction. Therefore, cyclopropane can be transformed into several useful structures in organic synthesis. Different methods have been described to achieve cyclopropanes such as, Simmons‐Smith reaction, decomposition of diazoalkanes and Michael‐Initiated ring closure (MIRC). Due to the absence of metals, this last method has been applied to the asymmetric organocatalytic synthesis of cyclopropanes, where the substrates activation is through the imine‐enamine intermediates formation or by hydrogen bonds. The asymmetric reaction consists of a domino reaction composed of a conjugate addition reaction and a cyclization reaction via intramolecular nucleophilic substitution. In this review, different asymmetric organocatalytic syntheses of the last two decades until 2021 are presented. With the intention to facilitate the reading of the review, an example of each paper was selected with the optimal reaction conditions and with the best organocatalyst producing the best yield and high stereoselectivity. [ABSTRACT FROM AUTHOR]

The synthesis of chiral proline-derived squaramide and thiosquaramide organocatalysts, which are capable of the dual activation in asymmetric reactions is reported. The (thio)squaramide moiety can form hydrogen bonds to activate the substrates and to stereocontrol the reaction, while the pyrrolidine unit can form enamines to activate carbonyl compounds via aminocatalysis. Comparing the performance of thiosquaramide to squaramide, the Diels–Alder reaction of (anthracen-9-yl)acetaldehyde and trans -β-nitrostyrene was examined, which has been investigated in the literature using quantum chemical calculations. Both squaramide and thiosquaramide gave excellent yields (up to 99%) and enantiomeric excess values (up to 98%). Moreover, their catalytic performance was compared in conjugate addition of lawsone to β,γ-unsaturated α-keto ester. [ABSTRACT FROM AUTHOR]

The cross-linked microbeads with average diameter of 106–300 μm, [poly(EGDMA-MATrp)], were obtained by copolymerization reaction of N-methacryloyl-L-(+)-tryptophan methyl ester (MATrp) with ethylene glycol dimethacrylate (EGDMA) and successfully applied as a heterogeneous catalyst in conjugate addition reaction of nitromethane to substituted 2-iminochromenes in aqueous media. A variety of 2-amino-4-(nitromethyl)-4H-chromene-3-carbonitriles has been synthesized in good yields. Polymeric microbeads were very durable and reused 5 times without a significant loss of activity. DFT calculations and experimental results revealed the significant role of π-π interactions as well as hydrogen bonding in the reaction mechanism. [ABSTRACT FROM AUTHOR]

[Display omitted] • Theoretical solid–liquid equilibrium curves and experimental studies have been used to identified new chiral DES. • A chiral choline chloride surrogate is an ideal chiral hydrogen bond acceptor for the preparation of new chiral DES. • The chiral DES have been thermally and structural characterized and used as reaction media in asymmetric organocatalysis. The present investigation centers on synthesizing, characterizing, and exploring the organocatalytic potential of a novel series of chiral deep eutectic solvents based on chiral (ammoniummethyl)pyrrolidine derivatives 1 – 3. Using the theoretical solid–liquid equilibrium curves, we have been able to identify three chiral deep eutectic solvents (CDESs) that have been thermally and structurally characterized and used as reaction medium in the conjugate addition of cyclohexanone to trans -β-nitrostyrene. Among these chiral deep eutectic solvents, the mixture 2 /EG: 1/3, where a chiral choline bromide surrogate is employed as the HBA, has shown good organocatalytic activity and recyclability in the studied model organocatalyzed process. Notably, this CDES exhibited higher activity and selectivity compared to organocatalyst 2 , and at the same level as that exhibited by the 2 /TFA catalyst under neat conditions. [ABSTRACT FROM AUTHOR]

Phytophenol dimerization, which is a radical-mediated coupling reaction, plays a critical role in many fields, including lignin biosynthesis. To understand the reaction, 2,2-diphenyl-1-picrylhydrazyl radical was used to initiate a series of phytophenol dimerization reactions in methanol. The products were identified using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-ESI-Q-TOF-MS/MS) analysis in situ. The identified products mainly included biphenols, magnolol, honokiol, gingerol 6,6′-dimers, 3,6-dimethoxylcatechol β,β′ dimer, euphorbetin, bis-eugenol, dehydrodiisoeugenol, trans-ε-viniferin, (+) pinoresinol, and (−) pinoresinol. Structure–function relationship analysis allowed four basic rules to be defined: meta-excluded, C–C bonding domination, ortho-diOH co-activation, and exocyclic C=C involvement. The exocyclic C=C involvement, however, required conjugation with the phenolic core and the para-site of the -OH group, to yield a furan-fused dimer with two chiral centers. Computational chemistry indicated that the entire process was completed via a radical coupling reaction and an intramolecular conjugate addition reaction. Similar results were also found for the horseradish peroxidase (HRP)-catalyzed coniferyl alcohol dimerization, which produced (+) and (−) pinoresinols (but no (−) epipinoresinol), suggesting that the HRP-catalyzed process was essentially an exocyclic C=C-involved phytophenol dimerization reaction. The reaction was highly diastereoselective. This was attributed to the intramolecular reaction, which prohibited Re-attack. The four basic rules and diastereoselectivity can explain and even predict the main products in various chemical and biological events, especially oxidase-catalyzed lignin cyclization. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Developing reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using these molecules for downstream studies in chemical biology and medicinal chemistry. Report here is accessing these target skeletons with high chemo‐, regio‐ and enantio‐selectivities through Pd(II)/chiral N,N'‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. Realization of 6‐6‐4 skeleton with a ring‐junction all‐carbon stereocenter is a one‐step process while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of allenes with alkynes, followed by Pd‐catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. Noteworthy is that chiral Bim ligand as a C2‐symmetric N,N'‐bidentateanionic ligand, designed by us, in coordinating with Pd catalyst was first applied to catalyze asymmetric 1,4‐conjugate addition reaction with the high catalytic performance (the reaction can be carried out in air). DFT calculations have been applied to understand how these reactions take place, the origins of enantioselectivity, and relative reactivities of different substrates. [ABSTRACT FROM AUTHOR]

Lower-rim Cinchona anchored calix[4]arene cationic catalysts were developed for asymmetric Michael addition of acetylacetone to β-nitrostyrenes. The desired Michael adducts were formed with high yields and enantioselectivities. Density functional theory investigations throw light on the catalyst–substrate interaction and the reaction mechanism. [ABSTRACT FROM AUTHOR]

A tandem intramolecular conjugate addition reaction was conducted with α,β-bisenones as selected Michael acceptors which were converted into 1,2,3-trisubstituted six-membered rings in the presence of activated sulfur nucleophiles. The products were obtained in good to excellent yields (maximum yield: 99%). Various substituted α,β-bisenones and sulfur nucleophiles were examined to understand the substrate scope of the reaction. Only one diastereomer was isolated, as lithium iodide mediated enolate trapping reactions improve the stereoselectivity of reactions involving 1,2,3-trisubstituted cyclohexanes. [ABSTRACT FROM AUTHOR]

The Michael reaction is a conjugate addition and is one of the most powerful methods with which to prepare functional molecules with a β‐stereogenic center. Despite its success in the formation of various asymmetric carbon–carbon and carbon–heteroatom bonds, enantioselective seleno‐Michael addition remains essentially unexplored. We report here a highly enantioselective Michael addition reaction of alkyl selenols to enones. This method conveniently introduces a Se atom to an electron‐deficient double bond asymmetrically. A chiral bifunctional N‐heterocyclic carbene (NHC)/thiourea catalyst was developed as a key ingredient that delivers chiral β‐seleno ketones with remarkable selectivity. This new catalyst and its mode of action support broad applications in the catalytic activation of nucleophilic reactions. [ABSTRACT FROM AUTHOR]

A palladium-catalyzed asymmeric conjugate addition of aryl boronic acids to medium-sized cycloalkenones followed by intramolecular aldol trapping is reported. The use of in situ formed [Pd/(QuinoxP*)] as the catalyst enables the synthesis of arylbicyclic scaffolds in good yields and with excellent stereocontrol (up to 7 : 1 dr, up to 99% ee). The reaction is applicable to a range of medium size ketoenone substrates and funcionalized aryl boronic acids, including heterocyclic compounds. [ABSTRACT FROM AUTHOR]

Synthesis of 2,3,6‐triisubstituted β‐carbolin‐1‐ones is disclosed using palladium‐catalyzed intramolecular amination of 3‐amino‐4‐(2‐bromophenyl)‐2‐pyridones prepared by the conjugate addition reaction of diethyl 2‐aminomalonate having a bulkier ketimine moiety to alkynyl imines. The transformation of the synthesized 3‐amino‐4‐(2‐bromophenyl)‐2‐pyridones using palladium‐catalyzed intramolecular amination produced 2,3,6‐trisubstituted β‐carbolin‐1‐ones in good to high yields. [ABSTRACT FROM AUTHOR]

Synthesis of 3,6‐disubstituted 4‐ethoxycarbonylpyranoindol‐1‐ones is developed using palladium‐catalyzed intramolecular amination of 3‐amino‐4‐(2‐bromophenyl)‐2‐pyrones prepared by the conjugate addition reaction of diethyl 2‐aminomalonate to alkynyl ketones. The transformation of the synthesized 3‐amino‐4‐(2‐bromophenyl)‐2‐pyrones via palladium‐catalyzed intramolecular amination afforded 3,6‐disubstituted 4‐ethoxycarbonylpyranoindol‐1‐ones. [ABSTRACT FROM AUTHOR]

The fluorinated‐liquid infused amphiphobic slippery interfaces exhibiting superior sliding of the beaded oil/water droplets, often suffer from durability and contamination issues. Here, the ability of 1) hexagonal packing of hydrocarbon sides in a selected "comb‐like" polymer and 2) its reversible phase transition at 51 °C was rationally exploited to achieve temperature‐assisted rapid (<1 minute) and repetitive (50 times) self‐healable amphiphobic solid‐slippery coating on both planar and geometrically‐complex substrates. The selected "comb‐like" polymer was strategically infused in a porous, hydrophilic and thick (≈4.8 μm) polymeric coating. The resultant solid and smooth interface exhibited sliding of beaded droplets of various liquids, including droplets of water, polar (ethanol, 1‐propanol, 1‐hexanol, DMSO, DMF), and non‐polar (decane, dodecane, diiodomethane) organic solvents, edible (vegetable oil), motor, engine (petrol, diesel, kerosene) and crude oils. [ABSTRACT FROM AUTHOR]

In this personal account, we describe our recent developments on the four types of amino Tf‐amide catalysts in asymmetric transformations. Firstly, axially chiral biaryl‐based secondary‐amino Tf‐amide catalyzed various stereoselective reactions via enamine intermediates. Secondly, pyrrolidine‐based secondary‐amino aliphatic Tf‐amide catalyzed asymmetric direct Mannich reaction. Thirdly, chiral primary‐amino aliphatic Tf‐amide catalyzed asymmetric direct aldol reaction and conjugate addition. Finally, modified chiral amino aromatic Tf‐amide catalyzed asymmetric transformations. These four different strategies are illustrated by using various organocatalyzed asymmetric transformations. [ABSTRACT FROM AUTHOR]

The objective of this study was to describe a cyclization reaction of photoredox generated ortho‐quinone methides using 1,3‐diketones for the synthesis of trifluoromethylated 4H‐1‐benzopyrans with moderate to high yields. This process resulted in in situ formation of trifluoromethylated ortho‐quinone methides from 2‐vinyl phenols with Umemoto's reagent, followed by conjugate addition and cyclization reaction of 1,3‐diketones. [ABSTRACT FROM AUTHOR]

Heterocycles possessing multiple substituents and stereogenic centers are important structural motifs in many compounds of interest. We present here stereoselective tandem transformation based on Cu‐catalyzed conjugate addition of Grignard reagents to heterocyclic Michael acceptors, which is followed by one‐pot trapping of in situ formed enolates with stabilized carbocations or their equivalents. The transformations are highly enantio‐ and diastereoselective with Josiphos‐type ferrocene ligand. The reaction of chiral metal enolates with onium compounds allows the installation of structurally attractive substituents on chromenone or piperidinone core. Moreover, cycloheptatrienyl and benzodithiolyl substituents can be further modified, thus expanding synthetic possibilities of this methodology. [ABSTRACT FROM AUTHOR]

Catalytic stereoselective additions with maleimides are useful one‐step reactions to yield chiral succinimides, molecules that are widespread among therapeutically active compounds but challenging to prepare when the maleimide is C‐substituted. We present the tripeptide H‐Pro‐Pro‐Asp‐NHC12H25 as a catalyst for conjugate addition reactions between aldehydes and C‐substituted maleimides to form succinimides with three contiguous stereogenic centers in high yields and stereoselectivities. The peptidic catalyst is so chemoselective that no protecting group is needed at the imide nitrogen of the maleimides. Derivatization of the succinimides was straightforward and provided access to chiral pyrrolidines, lactones, and lactams. Kinetic studies, including a Hammett plot, provided detailed insight into the reaction mechanism. [ABSTRACT FROM AUTHOR]

The divergent synthesis of cis‐, 4a‐epi‐cis‐, 2‐epi‐cis‐, and trans‐decahydroquinoline‐type poison‐frog alkaloids was achieved from the known chiral acetate 5 using a stereoselective Michael‐type conjugate addition reaction and an intramolecular aldol‐type cyclization with epimerization. The conformational control was achieved on the basis of the A1,3 strain in the starting material and the stereoelectronic effect. More specifically, the synthesis of cis‐251 A, cis‐209 J‐1, cis‐223F‐1, 4a‐epi‐cis‐251 A, 2‐epi‐cis‐251 A, and trans‐251 A bearing a seven‐carbon chain at the α‐position of the nitrogen atom on the piperidine nucleus was also realized. These compounds are expected to show selective and potent inhibitory activities toward nicotinic acetylcholine receptors. [ABSTRACT FROM AUTHOR]

Asymmetric vinylogous conjugate addition reactions constitute an essential class of enantioselective C−C bond‐forming transformations characterized by remote functionalization of substrates and the construction of distal stereocenters. After the renaissance of organocatalysis in 2000, vinylogous addition methodologies have seen new horizons of development. Cinchona alkaloids and some of their derivatives have appeared as efficient chiral catalysts in several organic transformations. Their non‐toxicity, low cost, availability in pseudo‐enantiomeric forms, and "open flask" reaction procedures have been the main reasons behind their success in asymmetric synthesis. These organocatalysts have also shown remarkable applications in vinylogous chemistry. This mini‐review covers the developments of asymmetric vinylogous conjugate addition (VCA) reactions under bifunctional cinchona alkaloids/derivatives catalysis. [ABSTRACT FROM AUTHOR]

Naturally occurring conjugated allenynes are of general interest owing to their potent and various biological activities. The 1,5‐H transfer of alka‐1,4‐diyn‐3‐yl amines would be one of the most straightforward yet challenging approaches to such compounds since, in principle, two regioisomers may be formed involving two C−C triple bonds. Herein, a catalytic recipe of copper halides with mixed oxidation states, i.e. CuCl/CuBr2, has been identified to address the issues of the side reaction of conjugate addition and the selectivity of 1,5‐H transfer of alka‐1,4‐diyn‐3‐yl amines in EATA (enantioselective allenation of terminal alkynes) reaction involving 2‐alkynals. This method provided various allenynes with excellent enantioselectivities, and was also applied to the first highly enantioselective total synthesis of natural product scorodonin. Mechanistic studies and DFT calculations elucidated the regioselectivity for the observed 1,5‐H transfer. [ABSTRACT FROM AUTHOR]

Chiral sulfones, a class of organic compounds with broad application prospects in organic synthesis and pharmaceutical chemistry, are an important part of building bioactive molecules or functional materials. In this paper, the advances and the state of synthesizing chiral sulfones by addition reactions are reviewed. The methods described in the manuscript are classified according to the types of reaction. Moreover, each chapter is arranged in chronological order. [ABSTRACT FROM AUTHOR]

Zerumbone is a naturally occurring humulene type sesquiterpene, isolated from the rhizomes of Zingiber zerumbet (L.) Smith with excellent therapeutic potential and is recognized as a valuable synthon for the construction of diverse array of natural product motifs. In this review, we intended to highlight our achievements in utilizing abundant natural product zerumbone and its derivatives for the development of pharmacologically relevant molecular scaffolds. We provided an account of the transition‐metal catalyzed 1,4‐conjugate addition reactions of zerumbone and its derivatives along with palladium‐catalyzed cross‐couplings, transition metal‐based Lewis acid promoted interrupted Nazarov cyclisation reaction with substituted indoles and transannular cyclizations, photo‐induced transformations of zerumbone and its epoxide. [ABSTRACT FROM AUTHOR]