Gold(I)-catalyzed intermolecular addition of carbon nucleophiles to 1,5- and 1,6-enynes

Gold(I)-catalyzed addition of carbon nucleophiles to 1,6-enynes gives two different type of products by reaction at the cyclopropane or at the carbene carbons of the intermediate cyclopropyl gold carbenes. The 5-exo-dig cyclization is followed by most 1,6-enynes, although those bearing internal alkynes and alkenes react by the 6-endo-dig pathway. The cyclopropane versus carbene site-selectivity can be controlled in some cases by the ligand on the gold catalyst. In addition to electron-rich arenes and heteroarenes, allylsilanes and 1,3-dicarbonyl compounds can be used as the nucleophiles. In the reaction of 1,5-enynes with carbon nucleophiles, the 5-endo-dig pathway is preferred.     

Introduction of glyco, peptido, carboxy, and alkyno substituents at the calixarene exo rim via the p-bromodienone route

The conceptually novel "p-bromodienone route", which allows the direct introduction of nucleophiles at the calixarene exo rim, has been extended to anionic C-nucleophiles (acetylides) to give chiral meta-substituted alkynocalix[4]arenes and to appropriate O-nucleophiles to obtain para-substituted glyco, peptido, and carboxy derivatives.     

Catalytic conjugate additions of nitrogen-, phosphorus-, and carbon-containing nucleophiles by amphoteric vanadyl triflate

A series of carbamates, amides, N-tosyl amides, (hetero)arenes, and hydrogen phosphines/phosphites has been examined as nucleophiles for (hetero)Michael-type additions to enones and enamides catalyzed by amphoteric vanadyl triflate under mild and neutral conditions. The newly developed C-N, C-P, and C-C bond-formation protocols were carried out smoothly in good to high yields without intervention of any 1,2-additions.     

Palladium‐Catalyzed Dearomative syn‐1,4‐Oxyamination

A palladium‐catalyzed dearomative syn‐1,4‐oxyamination protocol using non‐activated arenes has been developed. This one‐pot procedure utilizes arenophile chemistry, and the corresponding para‐cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn‐1,4‐oxyaminated products. The reaction conditions permit a range of arenes, as well as different O‐nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C?H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.     

Solid supported fluoronitroaryl triazenes as immobilized and convertible Sanger reagents--synthesis and SNAr reactions towards a novel preparation of 1-alkyl-5-nitro-1H-benzotriazoles

Synthesis of novel fluoronitroaryl triazenes in liquid phase and on solid support have been described; mild displacement of the fluoride ion with various nucleophiles provides access to substituted arenes which in turn can be cleaved to provide a unique access to 1-alkyl-5-nitro-1H-benzotriazole.     

N‐Trifluoromethylthiosaccharin: An Easily Accessible,Shelf‐Stable,Broadly Applicable Trifluoromethylthiolating Reagent

A new, electrophilic trifluoromethylthiolating reagent, N‐trifluoromethylthiosaccharin, was developed and can be synthesized in two steps from saccharin within 30 minutes. N‐trifluoromethylthiosaccharin is a powerful trifluoromethylthiolating reagent and allows the trifluoromethylthiolation of a variety of nucleophiles such as alcohols, amines, thiols, electron‐rich arenes, aldehydes, ketones, acyclic β‐ketoesters, and alkynes under mild reaction conditions.     

N‐Trifluoromethylthiosaccharin: An Easily Accessible,Shelf‐Stable,Broadly Applicable Trifluoromethylthiolating Reagent

A new, electrophilic trifluoromethylthiolating reagent, N‐trifluoromethylthiosaccharin, was developed and can be synthesized in two steps from saccharin within 30 minutes. N‐trifluoromethylthiosaccharin is a powerful trifluoromethylthiolating reagent and allows the trifluoromethylthiolation of a variety of nucleophiles such as alcohols, amines, thiols, electron‐rich arenes, aldehydes, ketones, acyclic β‐ketoesters, and alkynes under mild reaction conditions.     

Acid-promoted rearrangement of arylmethyl azides: applications toward the synthesis of N-arylmethyl arenes and polycyclic heteroaromatic compounds

An acid-promoted Aubé–Schmidt's rearrangement of arylmethyl azides provides a useful in situ iminium ion intermediate, which can be efficiently trapped by various nucleophiles. We report here the reaction of this iminium ion with aromatic nucleophiles to give N-arylmethyl arenes and the reaction with heteroaromatic compounds to give fused polycyclic heteroaromatic products in a formal [4+2] cycloaddition. The short synthesis of isocrytolepine, an antimalarial agent, further demonstrated the utility of this process.     

Brønsted Acid Catalyzed Oxygenative Bimolecular Friedel–Crafts‐type Coupling of Ynamides

A non‐metal approach for accessing α‐oxo carbene surrogates for a C−C bond‐forming bimolecular coupling between ynamides and nucleophilic arenes was developed. This acid‐catalyzed coupling features mild temperature, which is critical for the required temporal chemoselectivity among nucleophiles. The scope of nucleophiles includes indoles, pyrroles, anilines, phenols and silyl enolethers. Furthermore, a direct test of S_N2′ mechanism has been provided by employing chiral N,N′‐dioxides which also enlightens the nature of the intermediates in related metal‐catalyzed processes.     

Secondary benzylation with benzyl alcohols catalyzed by a high-valent heterobimetallic Ir-Sn complex

A highly efficient secondary benzylation procedure has been demonstrated using a high-valent heterobimetallic complex [Ir2(COD)2(SnCl3)2(Cl)2(mu-Cl)2] 1 as the catalyst in 1,2-dichloroethane to afford the corresponding benzylated products in moderate to excellent yields. The reaction was performed not only with carbon nucleophiles (arenes and heteroarenes) but also with oxygen (alcohol), nitrogen (amide and sulfonamide), and sulfur (thiol) nucleophiles. Mechanistic investigation showed the intermediacy of the ether in this reaction. An electrophilic mechanism is proposed from Hammett correlation.     

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.     

硝基芳环和硝基杂芳环中氢的替代亲核取代

氢的替代亲核取代反应(VNS)是与硝基芳环的亲电反应、亲核反应不同的一种新反应. 将VNS与硝基芳环的亲电反应、亲核反应做比较, 阐述了VNS的定义; 通过对竞比实验、速控步骤和动力学同位素效应的分析, 解释了VNS的反应机理; 分别从硝基芳环的结构、亲核试剂的类型和反应条件三方面讨论了影响VNS定位效应的因素; 介绍了VNS反应的应用, 尤其是VNS胺化反应在军事化学中的实际应用.     

Functionalization of the methylene groups of p-tert-butylcalix[4]arene: S-C,N-C,and C-C bond formation

Reaction of the calixarene derivative 7 with two exocyclic double bonds with carbon-, nitrogen-, oxygen-, or sulfur-containing nucleophiles afforded bis(spirodienone) derivatives substituted at two opposite methylene groups in a trans fashion. LiAlH(4) reduction of the bis(spirodienone) derivatives with two methylenes functionalized by thiomethoxy, diethyl malonate, or anilino substituents yielded trans methylene-substituted calix[4]arenes. Upon standing in solution, the calixarene derivative incorporating SMe groups on the bridges underwent trans right harpoon over left harpoon cis isomerization. An equilibration study performed on this calixarene derivative (tetrachloroethane-d(2), 430 K) indicated that the cis isomer is the form of lower free energy.     

Protolytic defluorination of trifluoromethyl-substituted arenes

A series of trifluoromethyl-substituted arenes were studied in their reactions with Br?nsted superacids. The products from these reactions suggest the formation of reactive electrophiles, such as carbocations, acylium cations or equivalent electrophilic species. As such, Friedel-Crafts-type reactions occur between these species and arene nucleophiles. NMR studies were done, and the results suggest the formation of an acyl group from the trifluoromethyl groups in the superacid.     

Synthesis of highly substituted furans by the electrophile-induced coupling of 2-(1-alkynyl)-2-alken-1-ones and nucleophiles

[reaction: see text] The coupling of 2-(1-alkynyl)-2-alken-1-ones with nucleophiles, either catalyzed by AuCl3 or induced by an electrophile, provides highly substituted furans in good to excellent yields under very mild reaction conditions. Various nucleophiles, including functionally substituted alcohols, H2O, carboxylic acids, 1,3-diketones, and electron-rich arenes, and a range of cyclic and acyclic 2-(1-alkynyl)-2-alken-1-ones readily participate in these cyclizations. Iodine, NIS, and PhSeCl have proven successful as electrophiles in this process. The resulting iodine-containing furans can be readily elaborated to more complex products using known organopalladium chemistry.     

High facial diastereoselectivity in intra- and intermolecular reactions of chiral benzylic cations

Chiral carbenium ions can be attacked by arene nucleophiles with high facial diastereoselectivity (dr >/= 94/6). Benzylic cations, such as 2, were generated under acidic conditions and reacted with arenes in intra- and intermolecular Friedel-Crafts alkylation reaction. The depicted reaction 1 --> 3 represents one example for the unprecedented, highly diastereoselective intermolecular Friedel-Crafts alkylation reactions which were observed in this study.     

Transition-Metal-Free Coupling of Polyfluorinated Arenes and Functionalized,Masked Aryl Nucleophiles

A chemoselective C(sp²)−C(sp²) coupling of sufficiently electron-deficient fluorinated arenes and functionalized N-aryl-N’-silyldiazenes as masked aryl nucleophiles is reported. The fluoride-promoted transformation involves the in situ generation of the aryl nucleophile decorated with various sensitive functional groups followed by a stepwise nucleophilic aromatic substitution (S_NAr). These reactions typically proceed at room temperature within minutes. This catalytic process allows for the functionalization of both coupling partners, furnishing highly fluorinated biaryls in good yields.     

The reaction of o-alkynylarene and heteroarene carboxaldehyde derivatives with iodonium ions and nucleophiles: a versatile and regioselective synthesis of 1H-isochromene, naphthalene, indole, benzofuran, and benzothiophene compounds

The reaction of o-alkynylbenzaldehydes 1 with different alcohols, silylated nucleophiles 5, electron-rich arenes 10, and heteroarenes 12 in the presence of the reagent IPy(2)BF(4), at room temperature, gave functionalized 4-iodo-1H-isochromenes 2, 6, 11, and 13 in a regioselective manner. When alkynes 16 and alkenes 19 and 20 were used as nucleophiles, a regioselective benzannulation reaction took place to form 1-iodonaphthalenes 17 and 1-naphthyl ketones 18, respectively. Moreover, the latter process has been adapted to accomplish the synthesis of indole, benzofuran, and benzothiophene derivatives (23, 27, and 28, respectively). The three patterns of reactivity observed for the o-alkynylbenzaldehyde derivatives with IPy(2)BF(4) stem from a common iodinated isobenzopyrylium ion intermediate, A, that evolves in a different way depending on the nucleophile present in the reaction medium. A mechanism is proposed and the different reaction pathways observed as a function of the type of nucleophile are discussed. Furthermore, the reaction of the o-hexynylbenzaldehyde 1 b with styrene was monitored by NMR spectroscopy. Compound III, a resting state for the common intermediate in the absence of acid, has been isolated. Its evolution in acid media has been also tested, thereby providing support to the proposed mechanism.     

Cross-coupling reactions by cooperative Pd/Cu or Ni/Cu catalysis based on the catalytic generation of organocopper nucleophiles

In this review, cross-coupling reactions by cooperative Pd/Cu or Ni/Cu catalysis based on catalytically generated organocopper nucleophiles are summarized. Compared to conventional methods based on the use of stoichiometric amounts of pre-synthesized organometallic reagents, these methods are powerful tools for the alkynylation, arylation, alkenylation, and alkylation of organic electrophiles, especially as they can be carried out in a highly step-economical manner with readily available starting materials based on simple arenes, carboxylic acids, alkenes, and alkynes as pre-nucleophiles.