Photoredox-Enabled Self-(3+2) Cyclization of Vinyldiazo Reagents: Synthesis of Cyclopentenyl α-Diazo Compounds

A photocatalytic self-(3+2) cycloaddition of vinyldiazo compounds is described, which provides cyclopentene derivatives with conservation of one diazo functional group. Experimental insights and density functional theory indicate that the reaction is triggered by an unusual single electron oxidation of vinyldiazo compounds, while the photolysis for the generation of free carbene species is not involved. The synthetic applications of the resulting cyclopentenyl α-diazo compounds were demonstrated based on the rich chemistry of the diazo functional group.     

Synthesis of an Orthogonally Protected Polyhydroxylated Cyclopentene from l‐Sorbose

The use of l ‐sorbose in the synthesis of functionalized cyclopentene derivatives was accomplished. These cyclopentene derivatives are related to those found in naturally occurring jatrophane frameworks and in other bioactive compounds. The formation of allyl α‐l ‐sorbopyranoside was a key synthetic step. Regioselective introduction of protecting groups was followed by the hydrolysis of the allyl glycoside to furnish a fully protected acyclic l ‐sorbose derivative. This acyclic intermediate was subsequently used to give an orthogonally protected polyhydroxylated cyclopentene, which has potential for further synthesis of bioactive compounds. The protected cyclopentene itself showed a clear cytotoxic activity when tested against a panel of human cancer cell lines (HT29, LS174T, SW620, A549, and HeLa cells).     

Brønsted Acid Catalyzed Friedel–Crafts‐Type Coupling and Dedinitrogenation Reactions of Vinyldiazo Compounds

The direct Friedel–Crafts‐type coupling and dedinitrogenation reactions of vinyldiazo compounds with aromatic compounds using a metal‐free strategy are described. This Brønsted acid catalyzed method is efficient for the formation of α‐diazo β‐carbocations (vinyldiazonium ions), vinyl carbocations, and allylic or homoallylic carbocation species via vinyldiazo compounds. By choosing suitable nucleophilic reagents to selectively capture these intermediates, both trisubstituted α,β‐unsaturated esters, β‐indole‐substituted diazo esters, and dienes are obtained with good to high yields and selectivity. Experimental insights implicate a reaction mechanism involving the selective protonation of vinyldiazo compounds and the subsequent release of dinitrogen to form vinyl cations that undergo intramolecular 1,3‐ and 1,4‐ hydride transfer processes as well as fragmentation.     

Brønsted Acid Catalyzed Friedel–Crafts-Type Coupling and Dedinitrogenation Reactions of Vinyldiazo Compounds

The direct Friedel–Crafts-type coupling and dedinitrogenation reactions of vinyldiazo compounds with aromatic compounds using a metal-free strategy are described. This Brønsted acid catalyzed method is efficient for the formation of α-diazo β-carbocations (vinyldiazonium ions), vinyl carbocations, and allylic or homoallylic carbocation species via vinyldiazo compounds. By choosing suitable nucleophilic reagents to selectively capture these intermediates, both trisubstituted α,β-unsaturated esters, β-indole-substituted diazo esters, and dienes are obtained with good to high yields and selectivity. Experimental insights implicate a reaction mechanism involving the selective protonation of vinyldiazo compounds and the subsequent release of dinitrogen to form vinyl cations that undergo intramolecular 1,3- and 1,4- hydride transfer processes as well as fragmentation.     

Gold‐Catalyzed Cycloaddition Reactions of Ethyl Diazoacetate,Nitrosoarenes, and Vinyldiazo Carbonyl Compounds: Synthesis of Isoxazolidine and Benzo[b]azepine Derivatives

Gold‐catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments.     

Gold‐Catalyzed Cycloaddition Reactions of Ethyl Diazoacetate,Nitrosoarenes, and Vinyldiazo Carbonyl Compounds: Synthesis of Isoxazolidine and Benzo[b]azepine Derivatives

Gold‐catalyzed cycloadditions of ethyl diazoacetate, nitrosoarenes, and vinyldiazo carbonyl species to yield isoxazolidine derivatives stereoselectively are described. Treatment of these isoxazolidine products with the same catalyst results in a novel 1,2‐H shift/[3,3] rearrangement to give benzo[b]azepine compounds. The mechanism of this skeletal rearrangement is elucidated with deuterium‐labeling experiments.     

Catalytic Living Ring Opening Metathesis Polymerisation: The Importance of Ring Strain in Chain Transfer Agents

A recently developed catalytic living ring opening metathesis polymerisation (ROMP) was investigated using a series of reversible chain transfer agents (CTA) carrying either cyclopentene or cyclohexene rings, differing only in ring strain. All cyclopentene derivatives examined showed significantly faster reaction rates than the corresponding cyclohexene derivatives. This resulted in lower molecular weight dispersities and better control of the molecular weight for the cyclopentene compared to the cyclohexene CTAs. Both Grubbs’ second and third generation catalysts could be employed in catalytic living ROMP using cyclopentene CTA derivatives. The kinetics of different CTAs were studied, block copolymers were synthesised and residual ruthenium quantified by ICP‐OES. All polymers were fully characterised by NMR, GPC and MALDI‐ToF mass spectrometry. The new cyclopentene CTAs are readily synthesised in a few straightforward steps and provide faster reaction kinetics than all previously reported reversible CTAs.     

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

The review is focused on recent developments of chemistry of synthetic analogs of natural compounds, isoflavone and homoisoflavone. The possible synthetic strategies to access heterocyclic analogs of these compounds starting from readily available 3-formylchromone and its derivatives (3-cyanochromone, 2-amino-3-formylchromone) and products of its condensation with simplest C- and N-nucleophiles are discussed. The structural features of the reaction products that depend on the nature of the reaction medium, structure of the starting compounds, and reagent ratio are considered. Particular attention is given to the application of the modern strategies of organic synthesis, namely green chemistry approaches, click reactions, domino reactions, etc. Examples of compounds of this group most promising for clinical application due to wide and pronounced pharmacological effects are given.

     

挂式-四氢双环戊二烯热裂解产物分布研究

研究了常压下, 温度为450～650 ℃, 停留时间为15.44～4.03 s条件下的JP-10 (挂式-四氢双环戊二烯)热裂解产物分布. 在相对较长的停留时间下, JP-10热裂解转化率对温度很敏感. 热裂解主要产物为甲烷、乙烯、丙烯、丁烯、丁二烯、环戊二烯、苯、甲苯、苯乙烯、环戊烯的乙烯基取代物及C5, C6异构体(戊二烯、环戊烯的甲基取代物、环己烯、己二烯和环戊二烯甲基取代物), 其中, C1～C4、环戊二烯、苯、甲苯、乙烯基取代环戊烯为初始产物.     

Modern encroachment in synthetic approaches to access nifty quinoline heterocycles

Quinoline and its derivatives have become significant compounds because of their variety of applications in medicine, synthetic chemistry, coordination chemistry, as well as in the field of industrial chemistry. This review will summarize the different conventional methods of synthesis of quinolines and also entrenching special technique approaches such as microwave-assisted synthesis, multicomponent reactions, solvent-free reaction conditions, ionic liquids, ultrasound promoted synthesis, phase-transfer catalyst, photocatalyst, heterogeneous, homogeneous, biocatalysis, etc.     

Linked drug-drug conjugates based on triterpene and phenol structures. Rational synthesis,molecular properties,toxicity and bioactivity prediction

One of the tasks of modern medicinal chemistry is to produce new molecules that have interesting and desired biological effects. In addition, the synthetic procedure for obtaining these compounds should be at least partially smart and rational e.g. “Lego” and green approaches. The study focuses on the synthesis of several hybrid type compounds that are expected to be characterized by beneficial bioactivities. In order to hybridize natural triterpene oleanolic acid and phenol structures, the linker-mode concept was selected. The synthetic goal was achieved in two stages. The first concerns the rapid introduction of the halogenoacidic linker to active phenols selected as a result of microwave-ultrasonic (MW-US) assisted O-alkylation with the use of 2-halogenoacetic acid. The next stage of the synthetic studies involves the reaction of phenoxyacetic acid derivatives obtained containing an active carboxylic group with oleanolic acid/oxime units by the methods typical of triterpene chemistry. Novel linked ester- and iminoester-type triterpene derivatives with phenols (thymol, eugenol, paracetamol, nipagins, naphthols, curcumin and genistein) were obtained and characterized. Additionally, based on the analysis of numerous references and selected methods of computational chemistry (Molinspiration Cheminformatics, Osiris Property Explorer and PASS method) the molecular parameters and the preliminary anti-inflammatory and antinociceptive activity characterising these molecules as potential drugs were calculated and predicted.     

Importance of Baylis-Hillman adducts in modern drug discovery

The Baylis-Hillman (BH) reaction plays a fascinating role in the field of synthetic and medicinal chemistry. BH adducts and their derivatives have been used as crucial synthons for the synthesis of various pharmaceutically useful natural products and compounds with carbocyclic or heterocyclic frameworks. This digest letter aims to discuss some key ideas for the synthesis of biologically active scaffolds using BH reaction and raise the awareness of this emerging research domain in modern drug discovery. In this review, we will present and discuss recent reports of various biologically active scaffolds derived from BH reaction, and their reported biological activities.     

Chromophoric binaphthyl derivatives

A short synthetic route is outlined, starting from bromo-BN derivatives, via halogen lithium exchange, subsequent Michael reaction with dimethylaminoacrolein, hydrolysis to the corresponding aldehyde, and final condensation with a benzothiazolium unit to produce a BN-pentamethinium system, which absorbs in the visible range around 450 nm. Enantiopure ligands show a decent Cotton effect in the CD spectrum. Preliminary data show potential of these compounds in the area of supramolecular chemistry (enantioselective recognition) and also for medicinal application (induction of apoptosis). [reaction: see text]     

Advancement in synthetic strategies of bisdimedones: Two decades study

Bisdimedones have emerged as an important and versatile moiety in the field of synthetic and medicinal chemistry. It is screened as a precursor for the synthesis of several heterocycles such as acridinediones, xanthenediones, thioxanthenes, and benzopyrans that exhibited immense pharmacological as well as industrial applications. Its extensive characteristics have attracted the scientists to develop various protocols for the synthesis of bisdimedones and their derivatives from the reaction of dimedone with several aldehydes under different environmental conditions using various types of catalysts. This review encapsulates the recent progress in the synthesis of bisdimedone derivatives under several reaction protocols such as the use of nanoparticles, ionic liquids, metal salts, simple organic compounds, and catalyst-free conditions, and so forth in the last 20 years.     

可见光促进的偕二氟烯烃制备与应用研究进展

偕二氟烯烃化合物在医药、材料、精细化工等领域具有广泛的应用,同时也是一类非常重要的用于制备各类复杂的有机氟化合物的有机合成中间体.可见光催化反应具有条件温和、绿色清洁等特点,已经成为有机化学中非常重要的合成手段之一.本文综述了近年来可见光促进的偕二氟烯烃化合物的制备及其在有机合成化学中的应用.     

Organocatalytic Atroposelective Aldol Condensation: Synthesis of Axially Chiral Biaryls by Arene Formation

Axially chiral compounds are of significant importance in modern synthetic chemistry and particularly valuable in drug discovery and development. Nonetheless, current approaches for the preparation of pure atropisomers often prove tedious. We demonstrate here a synthetic method that efficiently transfers the stereochemical information of a secondary amine organocatalyst into the axial chirality of tri‐ortho‐substituted biaryls. An aromatic ring is formed during the dehydration step of the described aldol condensation cascade, leading to highly enantioenriched binaphthyl derivatives. The fundamental course of the reaction is related to the biosynthesis of aromatic polyketides.     

Synthesis of novel isoxazoline-fused cispentacin stereoisomers

New isoxazoline-fused cispentacins were prepared by the 1,3-dipolar cycloaddition of nitrile oxides to β-amino esters containing a cyclopentene skeleton. This synthetic procedure gave regio- and diastereoisomers of the cispentacins. The synthetic route was extended to the synthesis of these compounds in enantiomerically pure form.     

Reporter resins for solid-phase chemistry

[reaction: see text] An analytical construct resin, designed to aid the analysis of solid-phase chemistry, has been mixed in a small proportion with a conventional resin. The analytical construct ("reporter resin") contains two orthogonal linkers that allow cleavage of either the synthetic intermediates (at linker 2) or their analytically enhanced derivatives (at linker 1). The convenient and rapid monitoring of each step in the syntheses of representative library compounds was possible using small resin aliquots.     

Chemistry and Applications of Functionalized 2,4-Thiazolidinediones

Thiazolidinedione (TZD) is one of the privileged heterocyclic rings and has shown many biological applications in medicinal chemistry and drug discovery. This review covers the synthetic approaches of TZD and its derivatives, different synthetic techniques for affording the desired regioselectivity and stereoselectivity, and the techniques that would enhance reaction conditions such as microwave, one-pot, or ultrasound synthesis. It focuses on synthetic challenges of glitazones and the transformation of other heterocycles to TZD. Moreover, the chemical and biological behavior of TZD through the substitution in the N3 position, modification of the C5 position, annealing in complex heterocyclic systems, and hybridization with other pharmacologically attractive moieties are discussed. All reactions mentioned are provided as possible with different reaction conditions, mechanisms, derivatives scope, yield and clarified by applications of such reactions in the construction of potential medicinal agents. The review also answers questions about rapid racemization of glitazones, their toxicity, considering TZD as pan-assay interference compounds (PAINS) or not, and the influence of saturation of 5-position of TZD in their biological activities. This review is a comprehensive guide to make informed decisions for construction of TZD derivatives with biological potentials.     

An efficient method for cyclopentene annulation onto alpha,beta-unsaturated ketones: W(CO)(5)(L)-catalyzed 5-endo-dig cyclization of 6-siloxy-5-en-1-ynes

[reaction: see text] A highly efficient method for the cyclopentene annulation onto alpha,beta-unsaturated ketones is described. Indium-mediated 1,4-propargylation onto alpha,beta-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives the 6-siloxy-5-en-1-yne derivatives, which undergo W(CO)(5)(L)-catalyzed 5-endo-dig cyclization to give the corresponding cyclopentene derivatives in good yield.