A general electron donor–acceptor complex for photoactivation of arenes via thianthrenation

General photoactivation of electron donor–acceptor (EDA) complexes between arylsulfonium salts and 1,4-diazabicyclo[2.2.2]octane with visible light or natural sunlight was discovered. This practical and efficient mode enables the production of aryl radicals under mild conditions, providing an unrealized opportunity for two-step para-selective C–H functionalization of complex arenes. The novel mode for generating aryl radicals via an EDA complex was well supported by UV-vis absorbance measurements, nuclear magnetic resonance titration experiments, and density functional theory (DFT) calculations. The method was applied to the regio- and stereo-selective arylation of various N-heterocycles under mild conditions, yielding an assembly of challengingly linked heteroaryl–(hetero)aryl products. Remarkably, the meaningful couplings of bioactive molecules with structurally complex drugs or agricultural pharmaceuticals were achieved to display favorable in vitro antitumor activities, which will be of great value in academia or industry.

General photoactivation of EDA complexes between arylsulfonium salts and 1,4-diazabicyclo[2.2.2]octane was discovered. This practical mode enables the generation of aryl radicals for C–H functionalization of arenes.     

铯盐促进的有机反应

铯盐如Cs₂CO₃, CsF等因在钯催化碳碳偶联, N, O, S的烃基化反应中表现出良好的性能而引起了人们的广泛关注. 介绍了铯盐在钯催化的Suzuki, Heck, Stille, Sonogashira反应, 烯醇盐的芳基化, 酚类的邻位芳基化以及羰基化反应中的促进作用. 同时还对铯盐参与的N, O, S等的烃基化反应进行了讨论, 并侧重于与其他碱金属盐的对比.     

Arylation with Unsymmetrical Diaryliodonium Salts: A Chemoselectivity Study

Phenols, anilines, and malonates have been arylated under metal‐free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new “anti‐ortho effect” has been identified in the arylation of malonates. Several “dummy groups” have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal‐free reagents.     

2-炔基苯胺与二芳基碘鎓盐的选择性芳基化/环化串联反应

有机高价碘试剂是一类环境友好、制备简单且性质温和的有机合成新试剂。近年来,有机高价碘试剂因表现出新颖、独特的反应性能而受到化学工作者广泛关注,成为有机合成重要研究领域之一。二芳基碘鎓盐是有机高价碘试剂的一个重要组成部分,是一类具有较高普适性的芳基化试剂,可用于羰基化合物、烯烃、炔烃和杂原子亲核化合物等的芳基化反应。目前,二芳基碘鎓盐作为芳基化试剂对具有单一芳基化位点化合物的芳基化已经有了非常广泛而深入的研究。对于具有两个甚至多个芳基化位点的化合物(如同时具有胺基和炔基),其芳基化选择性问题仍缺乏系统研究。特别是在多个芳基化位点共存时如何能够使芳基化发生在某一特定位点仍然是一大难题。这限制了二芳基碘鎓盐作为芳基化试剂更广泛的应用。因此,我们选用2-炔基苯胺(含有胺基和炔基两个芳基化位点)作为原料,通过溶剂的选择以及溶液酸碱性的调控来改变不同芳基化位点的反应活性,通过催化剂的调变来改变二芳基碘鎓盐芳基化反应的能力,从而找出最优条件实现底物分子的选择性芳基化反应,并利用剩余活性位点实现分子内的环化反应,从而实现芳基化-环化串联反应合成一系列N-芳基吲哚类化合物。在对模型底物进行条件筛选实验时发现,以2-乙基辛酸铜(Cu(OCOC8H17)2)作催化剂,二异丙基乙基胺(DIPEA)作碱,1,2-二氯乙烷(DCE)为溶剂,反应以最高93%的收率得到1,2-二苯基吲哚。使用该最优反应条件,一系列2-炔基苯胺都能与二芳基碘鎓盐很好地发生反应并且以良好到优秀的产率(71%–98%)得到目标产物N-芳基吲哚。此外,2-炔基苯胺与非对称的二芳基碘鎓盐也能发生反应,实验结果证明为位阻较小的芳基对胺基进行了N-芳基化反应。通过空白实验和对比实验,我们提出了可能的反应机理：二芳基碘鎓盐在铜催化剂作用下转化为亲电性的芳基活性中间体,该中间体与底物的胺基发生芳基化反应,然后芳基化产物在铜催化剂作用下环化生成N-芳基吲哚。该反应很好地解决了同时具有胺基和炔基两个芳基化位点的底物与二芳基碘鎓盐反应时C-芳基化和N-芳基化的竞争问题,选择合适反应条件使N-芳基化反应优先进行,为二芳基碘鎓盐的选择性芳基化反应提供了很好的实例,并为其它具有多个芳基化位点化合物的选择性芳基化反应提供了途径。     

Domino N‐/C‐Arylation via In Situ Generation of a Directing Group: Atom‐Efficient Arylation Using Diaryliodonium Salts

Both aryl components of diaryliodonium salts can be used in a domino one‐pot reaction via in situ generation of a directing group. A number of heterocycles undergo N‐arylation which is followed by ruthenium‐catalyzed C‐arylation. Notably the reaction extends well to unsymmetrical diaryliodonium salts with a number of highly selective examples shown.     

Arylation catalytique d'organophosphorés. Produits de l'arylation,catalysée par les sels de nickel (II), de composés du phosphore tricoordiné.

Analysis of the products from the nickel (II) bromide catalysed arylation of tricoordinated phosphorus compounds R₂P-Z (Z  H, Cl, SR, NR₂ pointed out that this arylation always takes place on phosphorus resulting at first in formation of pseudophosphonium salts. Only the aminophosphonium salts are stable under reaction conditions; the other salts undergo several transformations which can be brought together in a general reactivity scheme to account for all the side products. On regard to other heteroatoms these results point out a particular ability of phosphorus to be arylated under nickel (II) catalysis.The reaction with secondary phosphines can be applied to synthetise diarylphosphonium salts.     

Pd-catalyzed direct arylation of tautomerizable heterocycles with aryl boronic acids via C-OH bond activation using phosphonium salts

The first direct arylation via C-OH bond activation of tautomerizable heterocycles has been achieved using phosphonium salts, on the basis of a combination of the phosphonium coupling and Suzuki-Miyaura cross-coupling conditions. Optimal reaction condition is obtained through screening of phosphonium salts, Pd catalysts, and bases. The direct arylation via C-OH bond activation tolerates a variety of tautomerizable heterocycles and aryl boronic acids. The mechanism of the Pd-catalyzed phosphonium coupling is proposed to proceed via a domino seven-step process including the unprecedented heterocycle-Pd(II)-phosphonium species. Application of the Pd-catalyzed direct arylation via C-OH bond activation using PyBroP leads to the most efficient synthesis of the biologically important 6-arylpurine ribonucleoside in a single step from unactivated and unprotected inosine.     

Reaction of diazonium salts with transition metals—III: Palladium(0)-catalyzed arylation of unsaturated compounds with arenediazoium salts

Palladium (0) catalyzed reactions of arenediazonium salts for arylation of aliphatic and cyclic olefins and allylic alcohols, styrene and ethyl acrylate were studied. Effects of the olefinic compounds and other reaction variables on the arylation were presented. Arylpalladium species was proposed as the most plausible intermediated in this reaction.     

Palladium-Catalyzed Arylation and Vinylation of 2,3-Dihydrofuran with Hypervalent Iodonium Salts

The palladium-catalyzed arylation and vinylation of 2,3-dihydrofuran with aryl and alkenyl iodonium salts afforded 2-phenyl- or 2-alkenyl-2,5-dihydrofurans at room temperature in an aqueous medium.     

A ligand-free and base-free copper catalyzed reaction: arylation of ammonia and primary amines as their acetate salts

A ligand-free, base-free copper catalyzed arylation of ammonia and primary amines as their corresponding acetate salts are established. The Carboxylate group is believed to be catalyzing the arylation of ammonia. This reaction is specific for primary amines.     

Synthesis and use of mono- or bisxylyl linked bis(benzimidazolium) bromides as carbene precursors for C-C bond formation reactions

Two benzimidazolium moieties linked by one or two xylyls (m- and p-) have been synthesized, characterized and then they were used for Heck coupling reactions as in situ formed catalysts. Mono bridged salts are more efficient as compared to bisbridged salts. In addition, mono bridged salts were converted to Rh-NHC complexes which were tested as catalysts for the arylation of aldehydes.     

Visible‐Light‐Mediated Selective Arylation of Cysteine in Batch and Flow

A mild visible‐light‐mediated strategy for cysteine arylation is presented. The method relies on the use of eosin Y as a metal‐free photocatalyst and aryldiazonium salts as arylating agents. The reaction can be significantly accelerated in a microflow reactor, whilst allowing the in situ formation of the required diazonium salts. The batch and flow protocol described herein can be applied to obtain a broad series of arylated cysteine derivatives and arylated cysteine‐containing dipeptides. Moreover, the method was applied to the chemoselective arylation of a model peptide in biocompatible reaction conditions (room temperature, phosphate‐buffered saline (PBS) buffer) within a short reaction time.     

Thermally Induced Carbohydroxylation of Styrenes with Aryldiazonium Salts

The radical carbohydroxylation of styrenes with aryldiazonium salts has been achieved under mild thermal conditions. A broad range of aryldiazonium salts was tolerated, and the reaction principle based on a radical–polar crossover mechanism could be extended to carboetherification as well as to a two‐step, metal‐free variant of the Meerwein arylation leading to stilbenes.     

Silver Ion Promoted,PdII‐Catalyzed Arylation of Arenes with a Free Amine as Directing Group in Aqueous Medium

Palladium(II)‐catalyzed arylation of arenes with aryl boronic acids and a free amine as directing group in aqueous medium has been developed. High reactivity and chemoselectivity for the formation of carbon–carbon bonds were achieved by the use of soluble silver salts. The addition of water is crucial to improve the arylation yield.     

Hypervalent Iodine in Synthesis. VI. The Electrophilic Arylation of Diaryliodonium Salts to Sodium Telluride

Diaryliodonium salts readily take place electrophilic arylation at Te to afford symmetrical diaryl tellurides in good yields.     

High-yielding intramolecular direct arylation reactions with aryl chlorides

[reaction: see text] An N-heterocyclic carbene palladium catalyst system is used to promote direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls. An influence of the halide on the palladium precatalyst on catalyst activation has been revealed, as has a beneficial effect of NHC salts that allows the turnover numbers to be increased by simple addition of imidazolium salts to the reaction mixture.     

Metal-free, visible-light-mediated direct C-H arylation of heteroarenes with aryl diazonium salts

Visible light along with 1 mol % eosin Y catalyzes the direct C-H bond arylation of heteroarenes with aryl diazonium salts by a photoredox process. We have investigated the scope of the reaction for several aryl diazonium salts and heteroarenes. The general and easy procedure provides a transition-metal-free alternative for the formation of aryl-heteroaryl bonds.     

Diaryliodonium Salts Enabled Arylation,Arylocyclization, and Aryl-Migration

Our research interest focusing on synthetic methodology with diaryliodonium salts, is summarized in this account. Besides employing a dual activation strategy of C−I and ortho C−H bonds, we have introduced vicinal functional groups at ortho-positions of diaryliodonium salts, in which their unique reactivities have been explored in various processes, including arylation, diarylation, cascade annulation, benzocyclization, arylocyclization, and intramolecular aryl migration. The variety of mechanisms of these reactions that involves either transition metals, especially palladium in organometallic catalysis, or transition-metal free conditions, were discussed in the context.     

Base‐Mediated O‐Arylation of Alcohols and Phenols by Triarylsulfonium Triflates

A mild and efficient protocol for O‐arylation of alcohols and phenols (ROH) by triarylsulfonium triflates was developed under transition‐metal‐free conditions. Various alcohols, including primary, secondary and tertiary, and phenols bearing either electron‐donating or electron‐withdrawing groups on the aryl rings were smoothly converted to form the corresponding aromatic ethers in moderate to excellent yields. The reactions were conducted at 50 or 80 °C for 24 h in the presence of a certain base and showed good functional group tolerance. The base‐mediated arylation with asymmetric triarylsulfonium salts could selectively transfer the aryl groups of sulfoniums to ROH, depending on their inherent electronic nature. The mechanistic studies revealed that the reaction might proceed through the nucleophilic attack of the in situ formed alkoxy or phenoxy anions at the aromatic carbon atoms of the C?S bonds of triarylsulfonium cations to furnish the target products.     

Novel hexadentate imidazolium salts in the rhodium-catalyzed addition of arylboronic acids to aldehydes

Four novel hexadentate imidazolium salts were synthesized from hexakis(bromomethyl)benzene and 1-substituted imidazole. The arylation of aldehydes with arylboronic acids was effected conveniently and in high yields by a catalyst system generated in situ from these hexadentate imidazolium salts, [Rh(COD)Cl]₂ and a base.