基于C–H活化的炔烃聚合反应合成多功能稠(杂)环聚合物

稠(杂)环聚合物是一类重要的功能聚合物,因其优异的光电特性而被广泛应用于光电领域.这类聚合物的传统制备方法往往需要用到修饰有复杂官能团的稠(杂)环单体,这些单体种类有限且合成难度大,导致稠(杂)环聚合物的发展受到限制. C–H活化过程的发现与提出为利用惰性的C–H键作为潜在官能团提供了可能,有效避免了对单体进行复杂修饰的要求,大大扩增了单体的种类和来源.基于C–H活化的炔烃环化聚合反应,能够在聚合物骨架中原位直接形成稠(杂)环结构,具有原料简单易得、聚合效率高、产物结构丰富等诸多优势,因此受到广泛关注.本文分类总结了基于C–H活化的炔烃环化聚合领域的最新进展,包括合成手段和所得聚合物的性质与功能介绍,并对该领域的未来发展方向进行了展望.     

Synthesis of 4,5-diarylquinazolines: a system with cofacial aromatic rings. Diazines. Part 39

Using metallation reactions and Pd-catalyzed coupling, we report here two synthetic routes leading to eight new 4,5-di(hetero)arylquinazolines. Non-linear activity has been highlighted for some of these compounds with stacked aromatic rings.     

Regioselective C−H Trifluoromethylation and Its Related Reactions of (Hetero)aromatic Compounds

Fluorinated functional groups, including trifluoromethyl group, play important roles in the development of drugs, agrochemicals, and organic functional materials. Therefore, the development of highly effective and practical reactions to introduce fluorinated functional groups into (hetero)aromatic compounds is highly desirable. We have achieved several regioselective C−H trifluoromethylation and related reactions by electrophilic and nucleophilic activation of six-membered heteroaromatic compounds and steric protection of aromatic compounds. These reactions proceed in good to excellent yields, even on a gram scale, with high functional group tolerance, and are applicable to the regioselective trifluoromethylation of drug molecules. In this personal account, the background of the introduction reactions of fluorinated functional groups, our reaction designs to achieve regioselective C−H trifluoromethylation and the related reactions of (hetero)aromatic compounds are explained.     

Reductive Molybdenum‐Catalyzed Direct Amination of Boronic Acids with Nitro Compounds

The synthesis of aromatic amines is of utmost importance in a wide range of chemical contexts. We report a direct amination of boronic acids with nitro compounds to yield (hetero)aryl amines. The novel combination of a dioxomolybdenum(VI) catalyst and triphenylphosphine as inexpensive reductant has revealed to be decisive to achieve this new C?N coupling. Our methodology has proven to be scalable, air and moisture tolerant, highly chemoselective and engages both aliphatic and aromatic nitro compounds. Moreover, this general and step‐economical synthesis of aromatic secondary amines showcases orthogonality to other aromatic amine syntheses as it tolerates aryl halides and carbonyl compounds.     

Three-Component Suzuki–Knoevenagel Synthesis of Merocyanine Libraries and Correlation Analyses of Their Oxidation Potentials and Optical Band Gaps

The Suzuki coupling Knoevenagel condensation one-pot synthesis of boronic acids/esters, (hetero)aromatic bromo aldehydes and methylene active compounds is a highly practical consecutive three-component process to provide substance libraries with 60 donor-π-bridge-acceptor molecules, i.e., merocyanines in a broader sense, in moderate to excellent yield. As already seen with the naked eye, a broad variation of the optical properties becomes accessible using this practical synthetic tool. More systematically, correlation analyses upon plotting the optical band gaps against the first oxidation potentials of redox active systems of consanguineous series furnishes linear correlations and, by extension, two parameter plots (oxidation potential and emission maximum) planar correlations with the optical band gaps.     

One-pot propagation of (Hetero)Arylamines: Modular synthesis of diverse Amino-di(hetero)arylamines

Formal propagation of (hetero)arylamine is achieved via a one-pot Buchwald–Hartwig C–N cross-coupling and nitro reduction sequence, enabling a rapid modular synthesis of diverse amino-di(hetero)arylamines from (hetero)arylamines and halogenated nitrobenzenes. Various functionalized aromatic amines with different electronic and steric environments can be efficiently prolongated to formally incorporate another arylamino fragments. This approach has been successfully applied in the synthesis of more than forty amino-di(hetero)arylamines. The applicability of this method has also been demonstrated in the synthesis of oligoanilines and the tyrosine-kinase inhibitor Imatinib.     

Site‐Differentiated Polyboron Arenes Prepared by Direct C?H Borylation and Their Highly Selective Suzuki–Miyaura Cross‐Coupling Reactions

Di‐ and polyboron (hetero)arenes, site‐differentiated with MIDA boronyl (MIDA=N‐methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium‐catalyzed direct C H borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high‐yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki–Miyaura coupling (SMC) of the Bpin moiety being an essential step.     

Site‐Differentiated Polyboron Arenes Prepared by Direct C?H Borylation and Their Highly Selective Suzuki–Miyaura Cross‐Coupling Reactions

Di‐ and polyboron (hetero)arenes, site‐differentiated with MIDA boronyl (MIDA=N‐methyliminodiacetic acid) and pinacolato boronyl (Bpin), were prepared by an iridium‐catalyzed direct C H borylation of readily available (hetero)aryl MIDA boronates. The excellent synthetic uses of these multisite nucleophiles were demonstrated by the high‐yield production of a variety of multifunctionalized poly(hetero)arenes with the highly chemoselective Suzuki–Miyaura coupling (SMC) of the Bpin moiety being an essential step.     

Domino Carbopalladation/CH Functionalization Sequence: An Expedient Synthesis of Bis‐Heteroaryls through Transient Alkyl/Vinyl–Palladium Species Capture

A microwave‐assisted highly efficient intermolecular domino carbopalladation/C?H functionalization sequence has been developed to access bis‐heteroaryl frameworks in a single operation. The reaction involves carbopalladation of the halogenated acrylamides or phenylpropiolamides by the Pd(0) catalysis, followed by the direct (hetero)arylation to give products with good to excellent yields. The synthetic utility of this method was also extended towards the application of the Ugi‐adduct as the starting material.     

可见光促进的苯及衍生物去芳构化反应

总结了近年来可见光促进苯及其衍生物去芳构化反应的研究进展,主要分为基态与激发态化学两方面,并对该领域的发展前景进行了展望.     

para‐Selective C−H Borylation of (Hetero)Arenes by Cooperative Iridium/Aluminum Catalysis

para ‐Selective C−H borylation of benzamides and pyridines has been achieved by cooperative iridium/aluminum catalysis. A combination of iridium catalysts commonly employed for arene C−H borylation and bulky aluminum‐based Lewis acid catalysts provides an unprecedented strategy for controlling the regioselectivity of C−H borylation to give variously substituted (hetero)arylboronates, which are versatile synthetic intermediates for complex multi‐substituted aromatic compounds.     

An efficient synthesis of embelin derivatives through domino Knoevenagel hetero Diels-Alder reactions under microwave irradiation

The synthesis of novel pyrano embelin derivatives has been achieved through domino Knoevenagel hetero Diels-Alder reactions of embelin (1) with paraformaldehyde and electron rich alkenes. This synthetic approach is highly efficient when microwave irradiation is used.     

Mono-Aryl/Alkylthio-Substituted (Hetero)acenes of Exceptional Thermal and Photochemical Stability by the Thio-Friedel–Crafts/Bradsher Cyclization Reaction

The highly substituted mono-aryl/alkylthio-(hetero)acenes prepared in this study have been found to be thermally more stable (T_decomp.=331–354 °C) than the known di-aryl/alkylthio-substituted acenes by an average of 25 °C. They are also much more photostable at 254 and 365 nm (in both argon and air) than the parent anthracene and other reported anthracenes. The most photostable aryl/alkylthio-anthracenes at 254 nm were found to be 60–70 (in air) and 130 (in argon) times more stable in solution than the unsubstituted anthracene, and much more stable than known EDG/EWG-substituted anthracenes (EDG=electron-donating group, EWG=electron-withdrawing group) with an extended aromatic core. Furthermore, the acenes showed significantly higher photostability at 365 nm in both air and argon. The anthracenes were obtained by the novel thio-Friedel–Crafts/Bradsher cyclization reaction of hitherto unknown [o-(1,3-dithian-2-yl)aryl](aryl)methyl thioethers. The developed approach provides a general access to mono-aryl/alkylthio-substituted (hetero)acene frameworks containing at least three fused (hetero)aromatic rings. The characteristic feature of this approach, which leads to highly substituted acenes, is that the substituents, unlike in other methods, may be introduced at an early stage of the synthesis. DFT and TD-DFT calculations confirmed the stabilizing role of the aryl/alkylthio substituent in the mono-aryl/alkylthio-substituted anthracenes, which are the most stable anthracenes prepared to date. Their high photostability is mainly due to the quenching of singlet oxygen by the acene and the quenching of the acene S₁ state by molecular oxygen.     

Synthetic utility of gem-dibromomethylarenes in organic synthesis

Gem-dibromomethylarenes are considered as one of the valuable building blocks in the synthetic field because of their broad range of synthetic applications. These synthons serve as useful intermediates in accessing a varied range of (hetero) aromatic frameworks that can act as vital scaffolds in agrochemicals, medicinal chemistry, material sciences, etc. The additional organic transformations that can be performed using these vital reagents highlights its significance in the area of organic synthesis. This review aims at displaying some discoveries and subsequent improvements of this vital intermediate as an important building block in organic transformations.     

Solution Structure of Turbo‐Hauser Base TMPMgCl⋅LiCl in [D8]THF

Turbo‐Hauser bases are very useful and highly reactive organometallic reagents in synthesis. Especially TMPMgCl ? LiCl 1 (TMP=2,2,6,6‐tetramethylpiperidide) is an excellent base for converting a wide range of (hetero)aromatic substrates into highly functionalized compounds with a broad application in organic synthesis. The knowledge of its structure in solution is of essential importance to understand the extraordinary reactivity and selectivity. However, very little is known about the aggregation of this prominent reagent in solution. Herein, we present the THF‐solution structure of 1 by employing our newly elaborated DOSY NMR method based on external calibration curves (ECC) with normalized diffusion coefficients.     

Dual ligand approach increases functional group tolerance in the Pd-catalysed C–H arylation of N-heterocyclic pharmaceuticals

The excellent functional group tolerance of the Suzuki–Miyaura cross-coupling reactions has been decisive for their success in the pharmaceutical industry. Highly diversified (hetero)aromatic scaffolds can be effectively coupled in the final step(s) of a convergent synthetic route. In contrast, electrophilic Pd catalysts for non-directed C–H activation are particularly sensitive to inhibition by coordinating groups in pharmaceutical precursors. While C–H arylation enables the direct conversion of (hetero)aromatics without preinstalled functional or directing groups, its functional group tolerance should be increased to be viable in late-stage cross-couplings. In this work, we report on a dual ligand approach that combines a strongly coordinating phosphine ligand with a chelating 2-hydroxypyridine for the highly robust C–H coupling of bicyclic N-heteroaromatics with aryl bromide scaffolds. The catalyst speciation was studied via in situ XAS measurements, confirming the coordination of both ligands under the reaction conditions. The C–H activation catalyst was shown to be tolerant to a wide range of pharmaceutically relevant scaffolds, including examples of late-stage functionalization of known drug molecules.

Ligand combination of a 2-pyridone with traditional phosphines enables superior functional group tolerance in the C–H (hetero)arylation of pharmaceutically relevant N-heterocyclic scaffolds.     

Aromaticity in bridged heteroannulenes

The aromatic stabilities of bridged hetero[n]annulenes (n = even, odd) and the parent structures of hetero-[n]annulenes and hetero[n]polycycles have been predicted by the topological resonance energy, TRE, approach. The TRE criterion places bridged structures in all cases studied between the hetero[n]annulenes and hetero[n]polycyclic systems. The extra aromatic stability of the bridged heteroannulenes compared to heteroannulenes is attributed to homoaromatic interaction across the ring at the bridge sites. Available experimental evidence supports the theoretical results.     

Spirocyclic Iodonium Ylides for Fluorine-18 Radiolabeling of Non-Activated Arenes: From Concept to Clinical Research

Positron emission tomography (PET) is a powerful imaging tool for drug discovery, clinical diagnosis, and monitoring of disease progression. Fluorine-18 is the most common radionuclide used for PET, but advances in radiotracer development have been limited by the historical lack of methodologies and precursors amenable to radiolabeling with fluorine-18. Radiolabeling of electron-rich (hetero)aromatic rings remains a long-standing challenge in the production of PET radiopharmaceuticals. In this personal account, we discuss the history of spirocyclic iodonium ylide precursors, from inception to applications in clinical research, for the incorporation of fluorine-18 into complex non-activated (hetero)aromatic rings.     

Ascorbic Acid as an Initiator for the Direct CH Arylation of (Hetero)arenes with Anilines Nitrosated In Situ

Ascorbic acid (vitamin C) has been used as a radical initiator in a metal‐free direct C? H arylation of (hetero)arenes. Starting from an aniline, the corresponding arenediazonium ion is generated in situ and immediately reduced by vitamin C to an aryl radical that undergoes a homolytic aromatic substitution with a (hetero)arene. Notably, neither heating nor irradiation is required. This procedure is mild, operationally simple, and constitutes a greener approach to arylation.     

A new method for the determination of the absolute stereochemistry of aromatic and heteroaromatic alkanols using Mosher's esters

A list of the ¹H NMR chemical shifts of the methoxy group of α-methoxy-α-(trifluoromethyl)phenylacetic acid (Mosher's) esters of α- and β-(hetero)aromatic secondary alkanols has been compiled. Methoxy groups which are orientated syn to the (hetero)aromatic group in Mosher's conformational model have lower chemical shift values than those in the anti-orientation.