Search

An operationally simple catalyst-free protocol for the direct regiospecific synthesis of C3-arylated/alkenylated pyrroles has been developed. The enamine-intermediate, in situ generated from succinaldehyde and a primary amine, was trapped with activated carbonyls before the Paal–Knorr reaction in a direct multicomponent 'just-mix' protocol to furnish pyrroles in good yields. Several C3-substituted N -alkylpyrroles have been prepared under open-flask conditions, avoiding protection-deprotection chemistry. [ABSTRACT FROM AUTHOR]

Herein, we report the novel strategy for the synthesis of 4-enamino-5-phenyl-2,3-dihydroisothiazole 1-oxides (in other words α-phenyl β-enamino γ-sultims) based on the CSIC reaction. Particularly, readily available α-amino nitriles (the Strecker products) reacted with benzyl sulfinyl chloride to give the corresponding sulfinamides, which upon treatment with excess of LiHMDS converted into the target α-phenyl β-enamino γ-sultims. The method works well and tolerates strained 3- and 4-membered spirocyclic substituents. A preliminary in silico study indicated that the γ-sultim scaffold can be considered a promising pharmacophore template. [ABSTRACT FROM AUTHOR]

The cyclization of various nucleophiles, such as 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, hydrazones, hydroxylamine, amidines, thioglycolic esters, heterocyclic enamines and others, with 4-chlorocoumarins, containing an electron-withdrawing group at position 3, allows for a convenient synthesis of a great variety of benzo[c]coumarins and related fused coumarins. Suzuki–Miyaura reactions of coumarin-derived bis(triflates) result in formation of arylated coumarins with excellent regioselectivity that is controlled by electronic and steric features of the substrate. The combination of Suzuki–Miyaura with lactonization reactions of carba- and heterocyclic substrates allows for the synthesis of benzo[c]coumarins and of other fused coumarins. Domino Michael–retro-Michael–lactonization reactions of 1,3-bis(silyloxy)-1,3-butadienes with chromones provide a convenient access to hydroxylated benzo[c]coumarins. In a related approach, fused coumarins were prepared by domino reactions of heterocyclic enamines with chromone-3-carboxylic acids. 1 Introduction 2 Reactions of 3-Acceptor-4-chlorocoumarins 3 Reactions of Coumarin Triflates 4 Synthesis of Fused Coumarins 5 Conclusions [ABSTRACT FROM AUTHOR]

Enamines, containing nucleophilic amino groups and activated C=C bonds, are important building blocks, and widely used in the synthesis of heterocycles, natural products, and pharmaceuticals. In recent years, electrosynthesis has gradually developed into a powerful protocol for constructing chemical bonds due to its high economy, environmental friendliness, and mild reaction conditions. This review summarized the recent advances in the electrochemical transformation of enamines, including the construction of heterocyclic compounds, C(sp2)−H bond functionalization of enamines for synthesis of multi‐substituted alkenes, and the functionalization reactions of enamines via C=C double bond cleavage. The reaction conditions and mechanisms were systematically discussed, and the challenges and future directions of this field were included in this review. [ABSTRACT FROM AUTHOR]

Copper-mediated reactions of α-diazo-β-keto sulfonamides led to a range of products, including alkynesulfonamides, enamines, and α-halosulfonamides, with no evidence for intramolecular C–H insertion in any of the reactions, in contrast to the reactivity of the comparable α-diazo-β-oxo sulfones. Use of copper(II) triflate (5 mol%) led to the isolation of a series of alkynesulfonamides (up to 12% yield) and enamines (up to 64% yield). Use of copper(II) chloride (5 mol%) led to the formation, in addition, of α-halosulfonamides; use of stoichiometric amounts of copper(II) chloride/bromide enabled facile halogenation of the β-keto sulfonamide to form α-halosulfonamides (up to 63% yield). [ABSTRACT FROM AUTHOR]

Acridine scaffolds are present in biological and pharmaceutical molecules. However, achieving asymmetric functionalization of acridines remains challenging without an efficient and highly stereoselective approach. Here we demonstrate a facile electrooxidative asymmetric dehydrogenative coupling reaction of 9,10‐dihydroacridines with aldehydes. This method offers a sustainable and effective route to various chiral α‐alkylation of 9,10‐dihydroacridines in high yields with excellent enantioselectivities facilitated by readily available aminocatalyst. Detailed mechanistic studies and cyclic voltammetric analyses reveal that this asymmetric electrochemical reaction proceeds through redox‐mediated oxidation, followed by a nucleophilic attack with concurrently generated enamine. We anticipate that our research will open avenues for promising exploration in organocatalyzed electrochemical enantioselective transformations. [ABSTRACT FROM AUTHOR]

Enamines are versatile building blocks for the synthesis of biologically active compounds. Nevertheless, only a limited number of strategies have been reported for preparing trisubstituted enamines in a regio‐ and stereoselective manner. Herein, we report a regiocontrolled 6‐endo and 5‐exo tethered carboamination of propargylic alcohols for the synthesis of trisubstituted enamines. High regioselectivity was achieved through fine‐tuning of the amine protecting group during the Pd‐catalyzed carboamination. The introduced trifluoromethylated tether enables further stereoselective functionalizations, such as hydrogenation and fluorination. [ABSTRACT FROM AUTHOR]

Enamines are versatile building blocks for the synthesis of biologically active compounds. Nevertheless, only a limited number of strategies have been reported for preparing trisubstituted enamines in a regio‐ and stereoselective manner. Herein, we report a regiocontrolled 6‐endo and 5‐exo tethered carboamination of propargylic alcohols for the synthesis of trisubstituted enamines. High regioselectivity was achieved through fine‐tuning of the amine protecting group during the Pd‐catalyzed carboamination. The introduced trifluoromethylated tether enables further stereoselective functionalizations, such as hydrogenation and fluorination. [ABSTRACT FROM AUTHOR]

Enantiopure tetrahydroisoquinolines (THIQs), recognized as privileged skeletal structures in natural alkaloids, have attracted considerable attention from chemists due to their biological and pharmacological activities. Synthetic strategies for optically active THIQs have been rapidly and extensively developed in the past decades. In view of simplicity and atom economy, asymmetric reduction of N-heteroaromatics, imines, enamines, and iminium salts containing an isoquinoline (IQ) moiety should be the preferred approaches to obtain chiral THIQs. This review focuses on recent advances in the catalytic asymmetric synthesis of enantiopure THIQs via asymmetric reduction, including asymmetric hydrogenation, transfer hydrogenation, reductive amination, and deracemization. Highly enantioselective synthesis of THIQs was achieved via transition-metal-catalyzed asymmetric reduction and organocatalytic asymmetric reduction utilizing either catalyst activation or substrate activation strategy. Despite much progress in the enantioselective synthesis of THIQs, there still remain considerable opportunities and challenges for progress and developments in this field of research, particularly in the development of asymmetric catalytic systems for the direct reduction of IQs. [ABSTRACT FROM AUTHOR]

A one-carbon difluorocyclopropanation/ring-expansion has been developed for the chiral synthon Cyrene, which is obtained via cellulose pyrolysis. The ring-enlargement was achieved by converting Cyrene (dihydrolevoglucosenone) into an enamine, reacting it with an in situ-generated difluorocarbene, and then heating it to ring-open the cyclopropane. Access to the product provides access to fluorinated analogues of this valuable chiral biomass derivative. [ABSTRACT FROM AUTHOR]

Metal‐free, strong‐base‐free, and solvent‐free synthesis of alkenyl heteroarenes through PhNO2/PhNH2 mediated direct olefination of methyl substituted N‐heteroarenes with benzylic alcohols was described. Detailed mechanistic studies indicated that in situ formed imine was the active intermediate for the olefination. PhNO2 protected benzylic alcohols from overoxidation, and PhNH2 not only acted as the coupling partner for the formation of intermediate imine, but also provides an alkaline condition for the generation of enamine salt. Gram scale reaction and the synthesis of three pharmaceutically relevant conjugated olefins were also successful using this methodology. [ABSTRACT FROM AUTHOR]

We prepared numerous thiazole derivatives from push‐pull alkenes such as nitroenamines, enaminoester, and enaminonitrils in a two‐step reaction with thiocyanate ion. The first step was the formation of the thiocyanate‐substituted push‐pull alkene from an iodine‐containing intermediary. We demonstrated this sequence through the preparation and identification of the iodine‐substituted enamines. In the second step, thiazole ring closure took place in methanol, at room temperature. The imino group of the condensed thiazole ring systems was successfully acylated. The same reaction sequence with potassium selenocyanate resulted in two selenocyanate and a selenazole heterocyclic derivatives. The mechanism of the reaction with thiocyanate ion and the heterocycle formation was investigated by computational methods. We performed quantum chemical calculations, involving both the thermodynamic and the kinetic aspects of the ring closure reaction. [ABSTRACT FROM AUTHOR]

C(sp²)-H amination represents an attractive approach for the synthesis of enamines, which is intrinsically associated with the challenge of controlling of stereochemistry and primarily relying on transition-metal catalysis. Herein, a metal-free C(sp2)-H amination of a-substituted styrenes has been achieved, leading to stereodivergent formation of both E- and Z-enamines in 50 %-97 % yield under mild conditions by using PhI(OAc)2 as a green oxidant and ortho-phenylenediamines as nitrogen source. Interestingly, the Z/E selectivity can be controlled readily by switching the reaction medium. E-isomers were formed preferentially in THF, whereas n-hexane favored the formation of Z-isomers. Preliminary mechanistic studies suggested that in situ formed ortho-benzoquinone diimides are the key intermediates, and there is a correlation between solvent polarity and stereoselectivity. This study enriches the chemical repertoire of ortho-benzoquinone diimides particularly with respect to sustainable amination. [ABSTRACT FROM AUTHOR]

The article discusses the synthesis of new indeno[1,2-b]pyrroles and pyrrole-fused isocoumarins in aqueous media using a three-component domino reaction. These compounds have shown various biological activities, including antimicrobial properties. The study explores the feasibility of preparing these compounds, which are structurally similar to known antimicrobial agents, and evaluates their antibacterial activity against different strains. The results show promising antimicrobial activities, suggesting the potential of these compounds as novel antimicrobial agents. [Extracted from the article]

The present article provides an overview of our work related to cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles. As electrophiles, we used nitro-substituted benzoylacetones, 3-ethoxy-2-nitro-2-en-1-ones, 2-nitrobenzoyl chlorides, 4-chloro-3-nitrocoumarin, 2-nitromalonic aldehyde, 3-nitrochromone and 1-(2-chloro-5-nitrophenyl)prop-2-yn-1-ones. As nucleophiles, 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, (heterocyclic) enamines, hydroxylamine, hydrazines, amines and amino esters were employed. The products include a variety of nitro-substituted carbo- and heterocycles that are not readily available by other methods. The electron-withdrawing nitro group can be easily transformed into an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can be converted into other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium-catalyzed CH-arylation reactions. Inter- and intramolecular CH arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in SN Ar reactions. Various fused benzofuro[3,2- b ]pyridines were prepared by intramolecular SN Ar reactions of 2-(hydroxyphenyl)-3-nitropyridines. 1 Introduction 2 Cyclizations of 1,3-Bis(silyloxy)-1,3-butadienes 3 Cyclizations of Heterocyclic Enamines 4 Reactions of Simple Nitro-Substituted Heterocycles 5 Hydroamination Reactions of Alkynes 6 Miscellaneous 7 Conclusions [ABSTRACT FROM AUTHOR]

A novel protocol for the visible‐light‐driven synthesis of β‐trifluoromethylated enamines has been developed, which operates without the use of transition metals or any photocatalysts, utilizing trifluoromethylthiosulfonium salts as the source of trifluoromethyl groups under mild conditions. According to this new protocol, more than 40 products have been prepared in moderate to good yields. In addition to eliminating the need for expensive or toxic transition metals and photocatalysts, this new methodology proves its potential scalability through air‐stability, the use of safe and readily available reagents, a two‐step one‐pot procedure, and effective gram‐scale reactions. This innovative approach not only demonstrates promise for green chemical synthesis but also offers a new pathway for the advancement of fluorine chemistry in sustainable organic synthesis. [ABSTRACT FROM AUTHOR]

An unprecedented eco-friendly multi-component domino reaction for the synthesis of novel N,O-acetals is reported. The protocol involves sequential coupling, [1,5]-hydride transfer and hetero-Diels–Alder cyclization. This new strategy enables direct α,β-difunctionalization of cyclic amines utilizing enamines generated in situ. The methodology features high atom and step economy, excellent regioselectivity, a simple work-up procedure and molecular diversity. [ABSTRACT FROM AUTHOR]

A de novo synthesis of cyclobutene‐fused indoline derivatives via thermally induced intramolecular cyclization was reported. This approach efficiently yields valuable high‐strained cyclobute[b]indolines in moderate to high yields and enables further transformation into other valuable heterocycles, demonstrating its potential in organic synthesis. [ABSTRACT FROM AUTHOR]

The unusual reactivity of key enamine intermediates led to the formation of 3-methylamino-2-(2-nitrobenzoyl)-4H-naphthalen-1-one as an unexpected product in an attempted synthesis of the P. aeruginosa metabolite 2-benzyl-4(1H)-quinolone. Although the synthesis of the natural product has not been successful, this methodology allows for the easy preparation of novel derivatives carrying a carboxamide moiety at the C3 position. [ABSTRACT FROM AUTHOR]

We report the detailed mechanistic insights of L-proline catalyzed, solvent-controlled, regioselective Mannich reaction. Different solvation models were employed to understand the formation of critical intermediates. The seminal difference in the nature of H-acceptor solvents and H-donor solvents leads to variation in the attachment site on the reactant molecule. Our calculations suggest that the H-acceptor solvent exhibits selective non-covalent interaction with α-hydrogen atoms of the iminium group, facilitating the reactivity at the more hindered site, which results in the formation of a branched isomer. On the other hand, the H-donor solvent preferentially binds to the carboxylate group, thus enabling the reactivity to proceed from the less hindered carbon chain, leading to a linear isomer. The above distinct interactions force a regioselective generation of enamines. Thus, the iminium ion's site-specific solvent interaction has been observed to cause a switch in the regioselectivity. These enamines subsequently react with cyclic ketone to produce Mannich base with excellent enantioselectivity (>99%ee). [ABSTRACT FROM AUTHOR]

The asymmetric catalytic synthesis of 1,2-diamines has received considerable interest, especially in the last ten years, due to their presence in biologically active compounds and their applications for the development of synthetic building blocks, chiral ligands and organocatalysts. Synthetic strategies based on C–N bond-forming reactions involve mainly (a) ring opening of aziridines and azabenzonorbornadienes, (b) hydroamination of allylic amines, (c) hydroamination of enamines and (d) diamination of olefins. In the case of C–C bond-forming reactions are included (a) the aza-Mannich reaction of imino esters, imino nitriles, azlactones, isocyano acetates, and isothiocyanates with imines, (b) the aza-Henry reaction of nitroalkanes with imines, (c) imine–imine coupling reactions, and (d) reductive coupling of enamines with imines, and (e) [3+2] cycloaddition with imines. C–H bond forming reactions include hydrogenation of C＝N bonds and C–H amination reactions. Other catalytic methods include desymmetrization reactions of meso-diamines. [ABSTRACT FROM AUTHOR]

A copper‐catalyzed [3+2] annulation reaction of exocyclic enamines/enol ethers with 1,4‐benzoquinone esters has been developed, providing facile access to N,O‐spiroketals and spiroketals under mild conditions with broad substrate scope (26 examples, 71–94 % yields). Gram scale synthesis and chemical transformations demonstrated that this method is potentially useful in the synthesis of natural products and drugs containing a N,O‐ spiroketal moiety. The chiral N,O‐spiroketal could be obtained with 98 % ee after recrystallization, when a chiral SaBOX ligand was employed. [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]

The low‐electron count, air‐stable, platinum complexes [Pt(ItBu')(ItBu)][BArF] (C1) (ItBu=1,3‐di‐tert‐butylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuiPr)2][BArF] (C2) (ItBuiPr=1‐tert‐butyl‐3‐iso‐propylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuMe)2][BArF] (C3), [Pt(GePh3)(ItBuiPr)2][BArF] (C4), [Pt(GePh)3(ItBuMe)2][BArF] (C5) and [Pt(GeEt)3(ItBuMe)2][BArF] (C6) (ItBuMe=1‐tert‐butyl‐3‐methylimidazol‐2‐ylidene) are efficient catalysts (particularly the germyl derivatives) in both the silylative dehydrocoupling and hydrosilylation of electron rich alkenes derived from enamines. The steric hindrance exerted by the NHC ligand plays an important role in the selectivity of the reaction. Thus, bulky ligands are selective towards the silylative dehydrocoupling process whereas less sterically hindered promote the selective hydrosilylation reaction. The latter is, in addition, regioselective towards the β‐carbon atom of both internal and terminal enamines, leading to β‐aminosilanes. Moreover, the syn stereochemistry of the amino and silyl groups implies an anti Si−H bond addition across the double bond. All these facts point to a mechanistic picture that, according to experimental and computational studies, involves a non‐classical hydrosilylation process through an outer‐sphere mechanism in which a formal nucleophilic addition of the enamine to the silicon atom of a platinum σ‐SiH complex is the key step. This is in sharp contrast with the classical Chalk–Harrod mechanism prevalent in platinum chemistry. [ABSTRACT FROM AUTHOR]

The low‐electron count, air‐stable, platinum complexes [Pt(ItBu')(ItBu)][BArF] (C1) (ItBu=1,3‐di‐tert‐butylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuiPr)2][BArF] (C2) (ItBuiPr=1‐tert‐butyl‐3‐iso‐propylimidazol‐2‐ylidene), [Pt(SiPh)3(ItBuMe)2][BArF] (C3), [Pt(GePh3)(ItBuiPr)2][BArF] (C4), [Pt(GePh)3(ItBuMe)2][BArF] (C5) and [Pt(GeEt)3(ItBuMe)2][BArF] (C6) (ItBuMe=1‐tert‐butyl‐3‐methylimidazol‐2‐ylidene) are efficient catalysts (particularly the germyl derivatives) in both the silylative dehydrocoupling and hydrosilylation of electron rich alkenes derived from enamines. The steric hindrance exerted by the NHC ligand plays an important role in the selectivity of the reaction. Thus, bulky ligands are selective towards the silylative dehydrocoupling process whereas less sterically hindered promote the selective hydrosilylation reaction. The latter is, in addition, regioselective towards the β‐carbon atom of both internal and terminal enamines, leading to β‐aminosilanes. Moreover, the syn stereochemistry of the amino and silyl groups implies an anti Si−H bond addition across the double bond. All these facts point to a mechanistic picture that, according to experimental and computational studies, involves a non‐classical hydrosilylation process through an outer‐sphere mechanism in which a formal nucleophilic addition of the enamine to the silicon atom of a platinum σ‐SiH complex is the key step. This is in sharp contrast with the classical Chalk–Harrod mechanism prevalent in platinum chemistry. [ABSTRACT FROM AUTHOR]

[Display omitted] The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying C N connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta , was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a β -ketoenamine structure bearing a large amount of –NH groups and intramolecular H-bonds. TpTta was then post-modified by inserting imidazole (Im) and histamine (His) molecules, yielding the corresponding COFs, Im@TpTta and His@TpTta , respectively. As a result, their proton conductivities were surveyed under changeable temperatures (30–100 °C) and relative humidities (68–98 %), revealing a degree of temperature and humidity dependence. Impressively, under identical conditions, the optimum proton conductivities of the two post-modified COFs are 1.14 × 10−2 (Im@TpTta) and 3.45 × 10−3 S/cm (His@TpTta), which are significantly greater than that of the pristine COF, TpTta (2.57 × 10−5 S/cm). Finally, their proton conduction mechanisms were hypothesized based on the computed activation energy values, water vapor adsorption values, and structural properties of these COFs. Additionally, the excellent electrochemical stability of the produced COFs was expressed, as well as the prospective application value. [ABSTRACT FROM AUTHOR]

[Display omitted] Covalent organic frameworks (COFs) present bright prospects in visible light photocatalysis with abundant active sites and exceptional stability. Tailoring an established COF with photoactive group is a prudent strategy to extend visible light absorption toward broad photocatalysis. Here, a β-ketoenamine COF, TpBD-COF, constructed with 1,3,5-triformylphloroglucinol (Tp) and 4,4′-biphenyldiamine (BD), is tailored with azo to validate this strategy. The insertion of azo into BD affords 4,4′-azodianiline (Azo); TpAzo-COF is successfully constructed with Tp and Azo. Intriguingly, the insertion of azo enhances π-conjugation, thereby facilitating visible light absorption and intramolecular electron transfer. Moreover, TpAzo-COF, with an appropriate electronic structure and impressive specific surface area of 1855 m2 g−1, offers substantial active sites conducive to the reduction of oxygen (O 2) to superoxide. Compared with TpBD-COF, TpAzo-COF exhibits superior performance for blue light-driven oxidation of amines with O 2. Superoxide controls the selective formation of product imines. This work foreshadows the remarkable capacity of tailoring COFs with photoactive group toward broad visible light photocatalysis. [ABSTRACT FROM AUTHOR]

A convenient synthesis of functionalized aminoalkyl organophosphorus compounds bearing 3-, 4- or 5-coordinated phosphorus atom is based on readily available enamines and trivalent phosphorus acid esters. Radical addition of bis(trimethylsiloxy)phosphine to enamines proceeds regioselectively to give aminoalkylphosphonites, and their subsequent functionalization affords various derivatives of the target acids. The nucleophilic addition of hydrospirophosphorane to enamines also proceeds regioselectively to furnish α-aminoalkyl spirophosphoranes containing five-coordinated phosphorus atom. The resulting compounds are of interest as promising biologically active substances and water-soluble ligands. [ABSTRACT FROM AUTHOR]

Pyridine, an essential structure in drug development, shows a wide array of bioactivities according to its substitution patterns. Among the bioactive pyridines, meta-substituted pyridines suffer from limited synthetic approaches despite their significance. In this study, we present a condensation-based synthetic method enabling the facile incorporation of biologically relevant functional groups at the meta position of pyridine. This methodology unveiled the concealed reactivity of 3-formyl(aza)indoles as diformylmethane analogs for synthesizing dissymmetric di-meta-substituted pyridines without ortho and para substitutions. Furthermore, we uncovered resonance-assisted hydrogen bonding (RAHB) as the requirement for the in situ generation of enamines, the key intermediates of this transformation. Successful development of the designed methodology linked to wide applications—core remodeling of natural products, drug–natural product conjugation, late-stage functionalization of drug molecules, and synthesis of the regioisomeric CZC24832. Furthermore, we discovered anti-inflammatory agents through the functional evaluation of synthesized bi-heteroaryl analogs, signifying the utility of this methodology. Pyridine is an essential structural motif in medicinal chemistry and shows a wide range of bioactivities based on its substitution patterns, however, the meta-substitution of pyridine remains challenging. Here, the authors develop the synthesis of dissymmetric di-meta-substituted pyridines from 3-formyl(aza)indoles through the in situ generation of enamines via resonance-assisted hydrogen bonding, showcasing various synthetic applications in medicinal chemistry. [ABSTRACT FROM AUTHOR]

The present personalized account summarizes various cyclization reactions, including multicomponent and domino processes, which are directed towards the synthesis of complex heterocyclic products. Domino Knoevenagel/hetero‐Diels‐Alder reactions provide a synthesis of annulated quinol‐2‐ones. The combination of Knoevenagel reactions with [3+2] cycloadditions of nitrogen ylides afford complex spiroheteriocyclic products. Domino Knoevenagel/enamine cyclization reactions result in the formation of condensed purine analogues. Formal [3+3] cyclizations of pyridinium salts allow for a rapid assembly of bridged heterocyclic systems and include the employment of thioxindoles and cyclohexane‐1,3‐diones as dinucleophilic building blocks. The formal [3+3] cyclization of thioxindoles with fluoroaroyl chlorides, such as 2‐fluorobenzoyl chlorides and 2‐chloropyridine‐3‐carboxylic chloride, give rise to the synthesis of condensed benzothiophenes. The cyclization of heterocyclic enamines with diimines and triazines afford various purine analogues by domino [4+2]/retro [4+2] reactions. The formal [3+3] cyclization of 2,4,6‐tris(trifluoromethyl)‐1,3,5‐triazine with 1,3‐bis(silyloxy)‐1,3‐butadienes afford, depending on the conditions, 2,6‐bis(trifluoromethy)pyrid‐4‐ones or triazaadamantanone derivatives. Heating of 2‐ethynylpyridines with electron‐rich dienes afforded 2‐(2‐methoxyphenyl)pyridines by a domino [4+2]/retro [4+2] process. The reaction of 2‐ethynylpyridines with enones afforded indolizines by a formal [3+3] cyclization. The reaction of trifluoromethyl‐substituted 1,3‐diketones with lithiated alkynes afforded 3‐hydroxy‐pent‐4‐yn‐1‐ones. Formal [5+1] cyclization of the latter with urea afforded trifluoromethyl‐substituted pyridines. The Pd catalyzed formal [3+2] cyclizations of 2,3‐dihalopyridines with imines afforded a series of regioisomeric 4‐ and 7‐azaindoles. [ABSTRACT FROM AUTHOR]

Catalytic hydroboration and hydrosilylation have emerged as promising strategies for the reduction of unsaturated hydrocarbons and carbonyl compounds, as well as for the dearomatization of N-heteroarenes. Various catalysts have been employed in these processes to achieve the formation of reduced products via distinct reaction pathways and intermediates. Among these intermediates, N-silyl enamines and N-boryl enamines, which are derived from hydrosilylation and hydroboration, are commonly underestimated in this reduction process. Because these versatile intermediates have recently been utilized in situ as nucleophilic reagents or dipolarophiles for the synthesis of diverse molecules, an expeditious review of the synthesis and utilization of N-silyl and N-boryl enamines is crucial. In this review, we comprehensively discuss a wide range of hydrosilylation and hydroboration catalysts used for the synthesis of N-silyl and N-boryl enamines. These catalysts include main-group metals (e.g., Mg and Zn), transition metals (e.g., Rh, Ru, and Ir), earth-abundant metals (e.g., Fe, Co, and Ni), and non-metal catalysts (including P, B, and organocatalysts). Furthermore, we highlight recent research efforts that have leveraged these versatile intermediates for the synthesis of intriguing molecules, offering insights into future directions for these invaluable building blocks. [ABSTRACT FROM AUTHOR]

Aminocatalysis is a well‐established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO‐type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α‐alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4′‐dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity. [ABSTRACT FROM AUTHOR]

Aminocatalysis is a well‐established tool that enables the production of enantioenriched compounds under mild conditions. Its versatility is underscored by its seamless integration with various synthetic approaches. While the combination of aminocatalysis with metal catalysis, photochemistry, and stoichiometric oxidants has been extensively explored, its synergy with electrochemical activation remains largely unexplored. Herein, we present the successful merger of electrochemistry and aminocatalysis to perform SOMO‐type transformations, expanding the toolkit for asymmetric electrochemical synthesis. The methodology harnesses electricity to drive the oxidation of catalytically generated enamines, which ultimately partake in enantioselective radical processes, leading to α‐alkylated aldehydes. Crucially, mechanistic studies highlight how this electrochemical strategy is enabled by the use of a redox shuttle, 4,4′‐dimethoxybiphenyl, to prevent catalyst degradation and furnishing the coveted compounds in good yield and high enantioselectivity. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: The development of switchable solvent‐free multicomponent reactions to build high‐value‐added products is an important demand for organic synthesis. Herein, we detailed the successful implementation of a switchable strategy for the construction of diverse 4‐fluoroalkyl‐1,4‐dihydropyrimidines and 4‐fluoroalkyl‐pyrimidines via a solvent/additive‐free [3 + 2 + 1] annulation, starting from readily available enamines, trifluoroacetaldehyde hydrate or 1‐ethoxy‐2,2‐difluoroethanol and amidines hydrochloride. This reaction conforms to the concept of green synthesis, and provides a new avenue to access valuable fluorinated heterocycles. [ABSTRACT FROM AUTHOR]

Multicomponent condensation of cyanothioacetamide, carbonyl compounds, enamines and alkylating reagents initiated by the Knoevenagel reaction led to the formation of 2-thionicotinonitriles. The molecular and crystal structure of the prepared products was studied by single crystal X-ray diffraction method. [ABSTRACT FROM AUTHOR]

A simple procedure for the synthesis of (poly)cyclic O,O- and N,O-acetals from various enol ethers, N-acyl enamines or Boc-protected enamines has been developed. The key step is a photocatalytic Stork–Ueno-type cylization using the very simple metal-free conditions of catalytic eosin, diisopropylamine in the green solvent ethanol with blue LED irradition. [ABSTRACT FROM AUTHOR]

The goal of this study was directed to synthesize a novel class of annulated compounds containing difuro[3,2-c:3′,2′-g]chromene. Friedländer condensation of o-aminoacetyl derivative 3 was performed with some active methylene ketones, namely, 1,3-cyclohexanediones, pyrazolones, 1,3-thiazolidinones and barbituric acids, furnished furochromenofuroquinolines (4,5), furochromenofuropyrazolopyridines (6–8), furochromenofurothiazolopyridines (9,10) and furochromenofuropyridopyrimidines (11, 12), respectively. Also, condensation of substrate 3 with 5-amine-3-methyl-1H-pyrazole and 6-amino-1,3-dimethyluracil, as cyclic enamines, resulted in polyfused systems 13 and 14, respectively. In vitro antimicrobial efficiency of the prepared heterocycles against microbial strains exhibited variable inhibition action, where compound 3 was the most effective against all kinds of microorganisms. A significant cytotoxic activity was seen upon the annulation of the starting compound with thiazolopyridine (9 and 10) as well as pyridopyrimidine moieties (11, 12 and 14). The spectroscopic and analytical results were used to infer the structures of the novel synthesized compounds. [ABSTRACT FROM AUTHOR]

The synthesis of 2-acylindolizines, possessing a readily modifiable ketone group, is of significant importance as it provides versatile precursors for the preparation of various indolizines. However, due to the electronically less active and more sterically demanding nature of α,β-unsaturated ketones toward iminium formation with an aminocatalyst, the efficient one-pot transformation of α,β-unsaturated ketones for distinct 2-acylindolizines bearing sensitive groups represents a challenge for synthetic chemists. Herein, we report a weak-coordination-auxiliary amino-catalyzed approach that enables directed [3 + 2] cyclization of α,β-unsaturated ketones and N-heteroaryl ketones for the desired 2-acylindolizines via an iminium ion/enamine tandem sequence. A highly broad range of commercially available α,β-unsaturated ketones (internal, terminal, and cyclic enones) can act as coupling partners for readily accessible 2-acylindolizines relative to the existing state-of-the-art methods. Control experiments and in-depth DFT calculations highlight the importance of weakly coordinated glycine's carboxylic group in promoting the intramolecular cyclization and 1,5-proton transfer processes. [ABSTRACT FROM AUTHOR]

Novel 5'-methylamino-2'-nitro-m-terphenyls were obtained by the rearrangement of quaternary nitropyridinium salts under the action of aqueous alcoholic alkali and aqueous methylamine. Hantzsch 4-aryl-2-methyl-5-nitro-6-phenyl-1,4-dihydropyridines obtained by the cyclocondensation of nitrochalcones with various enamines were used as starting compounds. The oxidation of 1,4-dihydropyridines with sodium nitrite in acetic acid gave 4-aryl-2-methyl-5-nitro-6-phenylpyridines. The synthesized nitropyridines were alkylated with dimethyl sulfate and methyl fluorosulfonate. [ABSTRACT FROM AUTHOR]

The reaction of sulfonyl derivatives of 4-methylpyrazolo[5,1-c][1,2,4]triazines with N,N-dimethylformamide dimethyl acetal afforded a series of new enamines of pyrazolo-as-triazines. The synthesized compounds were studied in the reactions with some N-nucleophiles. It was found that the reaction of N,N-dimethylaminomethylene derivatives of 3-mesyl- and 3-tosylpyrazolo[5,1-c][1,2,4]triazines with hydrazine hydrate is accompanied by the as-triazine ring opening to give linear hydrazones, which was confirmed by X-ray diffraction data. [ABSTRACT FROM AUTHOR]

This document provides information on various compounds, specifically N-formyl derivatives, and their spectroscopic data. The compounds mentioned include a wide range of derivatives with different functional groups. The compounds were purified and their spectroscopic data were compared to existing literature, confirming their identities. The document also acknowledges the scholarship awarded to one of the researchers. [Extracted from the article]

A Lewis acid-mediated synthesis of 3-substituted quinolines from readily available 2-aminobenzyl alcohols and N,N′-dimethylenamine(one)s is reported. The Friedlander-type reaction described herein is modular and allows the installation of a variety of electron-withdrawing groups (COPh, CN, CO2Me, NO2, SO2Ph) at the 3-position of the quinoline nucleus to afford the final products in moderate to good yields. The reaction proceeds via transamination followed by the formation of a C–C bond by the involvement of a boron complex and aerobic oxidation to offer the product. [ABSTRACT FROM AUTHOR]

A library of regioisomeric monoterpene-based aminodiols was synthesised and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. The synthesis of the first type of aminodiols was achieved starting from (−)-8,9-dihydroperillaldehyde via reductive amination, followed by Boc protection and dihydroxylation with the OsO4/NMO system. Separation of formed stereoisomers resulted in a library of aminodiol diastereoisomers. The library of regioisomeric analogues was obtained starting from (−)-8,9-dihydroperillic alcohol, which was transformed into a mixture of allylic trichloroacetamides via Overman rearrangement. Changing the protecting group to a Boc function, the protected enamines were subjected to dihydroxylation with the OsO4/NMO system, leading to a 71:16:13 mixture of diastereoisomers, which were separated, affording the three isomers in isolated form. The obtained primary aminodiols were transformed into secondary derivatives. The regioselectivity of the ring closure of the N-benzyl-substituted aminodiols with formaldehyde was also investigated, resulting in 1,3-oxazines in an exclusive manner. To explain the stability difference between diastereoisomeric 1,3-oxazines, a series of comparative theoretical modelling studies was carried out. The obtained potential catalysts were applied in the reaction of aromatic aldehydes and diethylzinc with moderate to good enantioselectivities (up to 94% ee), whereas the opposite chiral selectivity was observed between secondary aminodiols and their ring-closed 1,3-oxazine analogues. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive review of recent advancements in the synthesis of tetrahydroindole compounds, which are important for natural alkaloids and synthetic medications. The authors discuss various methods for synthesizing these compounds, including intramolecular cyclization reactions and intermolecular condensations. They highlight the advantages of these methods, such as high yields, shorter reaction times, and low cost of reagents. The authors also identify areas for further development, particularly in the functionalization of the indole benzene ring. [Extracted from the article]

Organocatalytic asymmetric desymmetrization of prochiral cyclohexane-1,3-diones has been demonstrated through the merging of iminium and enamine activation. The tandem annulation reaction proceeds through a sequential oxa-Michael addition/intramolecular aldol reaction/[1,3]-amino oxetane rearrangement pathway. Mechanistic study using an 18O-water experiment suggests oxetane rearrangement instead of direct dehydration. The formation of other competing Rauhut-Currier products via alkoxyelimination was not observed. [ABSTRACT FROM AUTHOR]

Despite the significant role of pyruvic acid in biotransformations, the utilization of pyruvates in the field of catalytic asymmetric synthesis has been unexpectedly limited. This statement also applies to enamine catalysis, in which pyruvates seem to be challenging substrates. Recently, the first illustration of the asymmetric addition of pyruvic acid to β‐nitrostyrenes, catalyzed by a NahE enzyme using the enamine mechanism, has appeared in the literature. Now, we demonstrate pyrrolidine‐based catalyst can mimick enamine mechanism used by this enzyme to activate pyruvates in the asymmetric addition to structurally diverse nitroalkenes to produce highly enantioenriched Michael adducts without the limitations in substrate structures associated with biocatalysts. In addition to confirming that optically pure pyrrolidines can serve as ultimately small organic catalysts in pyruvate activation, we present an exceedingly simple and versatile method for the synthesis of optically pure γ‐nitro acids, which are precursors for well‐known active pharmaceutical ingredients namely GABA derivatives [ABSTRACT FROM AUTHOR]

The Ritter reaction of dialkyl benzyl carbinols with 3-methoxy- and 3-phenoxypropanenitriles afforded the corresponding 1-(2-methoxyethyl)- and 1-(2-phenoxyethyl)-3,3-dialkyl-3,4-dihydroisoquinolines. Likewise, benzo[f]isoquinoline derivatives were synthesized from 2-methyl-3-(naphthalen-1-yl)-propan-2-ol. The obtained compounds were shown to have the imine structure, but they exhibited enamine properties. In particular, their reactions with oxalyl chloride resulted in pyrrole annulation. [ABSTRACT FROM AUTHOR]

Sulfur-protected enantiomerically pure 1-phosphanorbornane aldehyde 5 is obtained in good yield via Swern oxidation of the previously reported 1-phosphanorbornane alcohol. The aldehyde is further used to prepare a novel sulfur-protected 1-phosphanorbornane enamine. [ABSTRACT FROM AUTHOR]

β‐Keto‐enamine‐linked 2D covalent organic frameworks (COFs) have emerged as highly robust materials, showing significant potential for practical applications. However, the exclusive reliance on 1,3,5‐triformylphloroglucinol (Tp aldehyde) in the design of such COFs often results in the production of non‐porous amorphous polymers when combined with certain amine building blocks. Attempts to adjust the crystallinity and porosity by a modulator approach are inefficient because Tp aldehyde readily forms stable β‐keto‐enamine‐linked monomers/oligomers with various aromatic amines through an irreversible keto‐enol tautomerization process. Our research employed a unique protection‐deprotection strategy to enhance the crystallinity and porosity of β‐keto‐enamine‐linked squaramide‐based 2D COFs. Advanced solid‐state NMR studies, including 1D 13C CPMAS, 1H fast MAS, 15N CPMAS, 2D 13C−1H correlation, 1H−1H DQ‐SQ, and 14N−1H HMQC NMR were used to establish the atomic‐level connectivity within the resultant COFs. The TpOMe‐Sqm COFs synthesized utilizing this strategy have a surface area of 487 m2 g−1, significantly higher than similar COFs synthesized using Tp aldehyde. Furthermore, detailed time‐dependent PXRD, solid‐state 13C CPMAS NMR, and theoretical DFT studies shed more light on the crystallization and linkage conversion processes in these 2D COFs. Ultimately, we applied this protection‐deprotection method to construct novel keto‐enamine‐linked highly porous organic polymers with a surface area of 1018 m2 g−1. [ABSTRACT FROM AUTHOR]

β‐Keto‐enamine‐linked 2D covalent organic frameworks (COFs) have emerged as highly robust materials, showing significant potential for practical applications. However, the exclusive reliance on 1,3,5‐triformylphloroglucinol (Tp aldehyde) in the design of such COFs often results in the production of non‐porous amorphous polymers when combined with certain amine building blocks. Attempts to adjust the crystallinity and porosity by a modulator approach are inefficient because Tp aldehyde readily forms stable β‐keto‐enamine‐linked monomers/oligomers with various aromatic amines through an irreversible keto‐enol tautomerization process. Our research employed a unique protection‐deprotection strategy to enhance the crystallinity and porosity of β‐keto‐enamine‐linked squaramide‐based 2D COFs. Advanced solid‐state NMR studies, including 1D 13C CPMAS, 1H fast MAS, 15N CPMAS, 2D 13C−1H correlation, 1H−1H DQ‐SQ, and 14N−1H HMQC NMR were used to establish the atomic‐level connectivity within the resultant COFs. The TpOMe‐Sqm COFs synthesized utilizing this strategy have a surface area of 487 m2 g−1, significantly higher than similar COFs synthesized using Tp aldehyde. Furthermore, detailed time‐dependent PXRD, solid‐state 13C CPMAS NMR, and theoretical DFT studies shed more light on the crystallization and linkage conversion processes in these 2D COFs. Ultimately, we applied this protection‐deprotection method to construct novel keto‐enamine‐linked highly porous organic polymers with a surface area of 1018 m2 g−1. [ABSTRACT FROM AUTHOR]