Kedong Yuan

Iridium‐Catalyzed Oxidant‐Free Dehydrogenative CH Bond Functionalization: Selective Preparation of N‐Arylpiperidines through Tandem Hydrogen Transfers

In addition to creating efficient and selective methodologies, the rise of green chemistry has led organic chemists and chemical industry to take into account the impact of these processes on the environment. Among the different ecofriendly approaches, homogeneous metal-catalyzed hydrogen autotransfers aimed at developing benign and atom-efficient protocols for the construction of carbon–heteroatom or carbon–carbon bonds have attracted considerable interest. In these reactions, the transient formation of unsaturated carbonyl or imine intermediates, arising from the dehydrogenation of alcohols or amines acting as alkylating reagents, has been successfully used for the preparation of a-alkylated carbonyl derivatives and amines accompanied by the formation of either water or valuable ammonia as the only side product. Owing to the potential of these transformations, recent developments have focused on the preparation of welldefined ruthenium and iridium complexes to allow more selective and milder reaction conditions, water soluble or reusable catalysts, and continuous flow approaches. In addition, the appealing amination from ammonia to afford alkylated amines has been reported by several groups. However, to date no tandem methodologies based on hydrogen autotransfer involving three different partners have been reported. Recently, we achieved the unprecedented oxidant-free dehydrogenation of cyclic N-benzyl and N-alkylamines using a ruthenium(II)–arene catalyst (A ; Scheme 1) featuring a phosphinesulfonate chelate. This reactivity involves hydrogen autotransfers and was successfully applied to the

Benzenesulfonyl chlorides: new reagents for access to alternative regioisomers in palladium-catalysed direct arylations of thiophenes

The palladium-catalysed coupling of benzenesulfonyl chlorides with thiophene derivatives allows regioselective access to β-arylated thiophenes. The reaction proceeds with easily accessible catalyst, base and substrates, without oxidant or ligand and tolerates a variety of substituents on both the benzene and thiophene moieties.

Regioselective Pd‐Catalyzed Methoxycarbonylation of Alkenes Using both Paraformaldehyde and Methanol as CO Surrogates

In recent years, considerable effort has focused on the development of novel carbonylative transformations using CO surrogates. Consequently, toxic CO gas can be replaced by more convenient inorganic or organic carbonyl compounds. Herein, the first regioselective methoxycarbonylation of alkenes with paraformaldehyde and methanol as CO substitutes is reported. This new procedure is applicable to a series of alkenes in the presence of a palladium catalyst under relatively mild conditions and is highly atom efficient.

Regiocontroled Palladium-Catalysed Direct Arylation at Carbon C2 of Benzofurans using Benzenesulfonyl Chlorides as the Coupling Partners

The regioselective palladium‐catalysed direct arylation of benzofurans with aryl halides is a challenging reaction because carbons C2 and C3 display similar reactivity. Such couplings generally lead to mixtures of C2 and C3 arylation products together with C2,C3 diarylation products. We found that the use of benzenesulfonyl chlorides instead of aryl halides as the coupling partner allows for controlling the regioselectivity of the palladium‐catalysed arylation of benzofurans in favour of carbon C2. This method tolerates a variety of substituents on the benzenesulfonyl derivative.

Access to Alternative Regioisomers for Palladium‐Catalysed Direct Arylations of (Benzo)thiophenes

effort has been expended toward developing such metal-catalysed direct arylation reactions for the synthesis of b-arylated (benzo)thiophenes (Figure 1, right). In recent years, a few examples of such b-arylations have been reported using new catalysts and/or reaction conditions. The first example of direct C3 arylation of a thiophene derivative was reported by Miura et al. , using a thiophene bearing a carboxanilide function at C2 with phenyltriflate as the coupling partner, employing Pd(OAc)2 associated to P(o-biphenyl)(tBu)2 as the catalyst (Scheme 1, top). [4a] The regioselectivity of the phenylation depends on the nature of the carboxanilide function, as only secondary amides led to the C3 arylated product. Similarly, Studer and co-workers have reported the oxidative coupling of 2-pyridylthiophene with arylboronic acids using Pd(OAc)2 or [RhCl(C2H4)2]2/P[p-(CF3)C6H4]3 catalysts. 2,2,6,6-Tetramethylpiperidine-N-oxyl radical (TEMPO) was used as a stoichiometric oxidant (Scheme 1, top). The 2-pyridyl group served as ortho-directing groups to mediate the b-arylation. In 2011, Bach et al. reported that thiophenes substituted at C3 by CH2COOEt or CH2PO(OEt)2 undergo a regioselective oxidative coupling reaction at C4 with various aryl boronic acids in the presence of silver oxide, cesiumtrifluoroacetate [Cs(tfa)] , benzoquinone (BQ), and Pd(tfa)2 catalyst in trifluoroacetic acid as the solvent (Scheme 1, middle). This procedure has been very recently extended to a broad range of substrates. In 2009, Itami and co-workers have established a catalytic system that promotes the b-selective arylation of thiophene derivatives with aryl iodides. These b-functionalisations were obtained using PdCl2 associated to a phosphite ligand (Scheme 1, middle). It should be noted that his procedure does not require the presence of a directing group on the thiophene derivative. Studer and Itami have also developed a method for the b-arylations of thiophenes with arylboronic acids under Pd/TEMPO catalysis (Scheme 1, bottom). In 2012, Oi et al. described the direct arylation of (benzo)thiophenes with aryltrimethylsilanes. The use of PdCl2(MeCN)2 catalyst in the presence of CuCl2 as oxidant also gives the b-arylated (benzo)thiophenes (Scheme 1, bottom). In this context, Glorius and co-workers have recently reported the first heterogeneously catalysed C H arylation of benFigure 1.

Eco‐Friendly Solvents for Palladium‐Catalyzed Desulfitative CH Bond Arylation of Heteroarenes

Herein, we report the Pd-catalyzed regioselective direct arylation of heteroarenes in which benzenesulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling that can be performed in diethyl carbonate (DEC) or cyclopentyl methyl ether (CPME) as green and renewable solvents or even in neat conditions instead of dioxane or dimethylacetamide (DMA). Under these solvent conditions, the reaction proceeds with a wide range of heteroarenes. C2- or C5-arylated products were obtained with furan and pyrrole derivatives. Benzofuran was also arylated regioselectively at the C2-position, whereas the reaction proceeds selectively at the C3- or C4-positions if thiophenes and benzothiophenes are used. Moreover, in some cases, especially with 1-methylindole, solvent-free conditions afforded better regioselectivities and/or yields than the reaction performed in the presence of solvents.

Palladium-Catalyzed Iterative C−H Bond Arylations: Synthesis of Medium-Size Heterocycles with a Bridgehead Nitrogen Atom

Condensed N‐heterocycles were prepared by using iterative C−H bond activation reactions catalyzed by palladium. The first step consists of a palladium‐catalyzed direct desulfitative C−H bond arylation of brominated N‐benzylpyrrole derivatives with benzenesulfonyl chlorides. The presence of the bromine atom allows the formation in the second step of several N‐heterocycles with five‐, six‐, or seven‐membered rings by a palladium‐catalyzed intramolecular C−H bond arylation.

Perfluorocyclohexene bridges in inverse DiArylEthenes: synthesis through Pd-catalysed C–H bond activation, experimental and theoretical studies on their photoreactivity

The palladium-catalysed direct di-heteroarylation of 1,2-dichloroperfluorocyclohexene with a variety of heteroarenes gives rise in to a new family of 1,2-di(heteroaryl)perfluorocyclohexenes. These derivatives do not exhibit photoreactivity and this unexpected outcome is explained by calculations demonstrating the lack of reactive isomers.

Reactivity of bromofluorenes in palladium-catalysed direct arylation of heteroaromatics

The palladium-catalysed direct arylation using bromofluorenes and heteroaromatics as the coupling partners proceeded in moderate to high yields using only 0.1–0.5 mol% Pd(OAc)2 or 1 mol% PdCl(C3H5)(dppb) as the catalyst and KOAc as the base. A wide variety of heteroarenes have been successfully employed, allowing their properties to be easily tuned. From 2,7-dibromofluorene, successive arylations allow the introduction of two different heteroarenes at carbons C2 and C7.

Desulfitative Pd-catalysed coupling reaction using benzenesulfonyl chlorides and enones as the coupling partners

The reaction of benzenesulfonyl chlorides with enones was investigated. β-Ionone and benzalacetone in the presence of a palladium catalyst were found to afford the conjugate addition products instead of the expected Heck type products. The reaction tolerates a wide variety of substituents on the benzenesulfonyl chloride. It should be noted that no cleavage of the C–Br and C–I bonds was observed in the course of the reactions with 4-bromo- or 4-iodo-benzenesulfonyl chlorides, allowing further transformations. For example, using 4-bromobenzenesulfonyl chloride as the central unit, consecutive conjugate addition following arylations allowed access to substituted bi(hetero)aryls.