Zhengkun Yu

Rhodium-Catalyzed Regioselective C−H Functionalization via Decarbonylation of Acid Chlorides and C−H Bond Activation under Phosphine-Free Conditions

Efficient rhodium(I)-catalyzed regioselective functionalization of aromatic C-H bonds has been realized with acid chlorides as the coupling partners via decarbonylation and C-H activation under phosphine-free conditions.

Palladium-catalyzed cross-coupling of internal alkenes with terminal alkenes to functionalized 1,3-butadienes using C-H bond activation: efficient synthesis of bicyclic pyridones.

Transition-metal-catalyzed cross-coupling through C H bond activation is emerging as one of the most important tools for carbon–carbon bond formation. In general, vinylogous compounds can be synthesized by Wittig, Heck, and Suzuki reactions, from the condensation of carbonyl compounds, C H addition to alkynes, or by means of organometallic alkenyl compounds, but direct alkenylation using C H bond activation remains particularly attractive for constructing carbon–carbon double bonds owing to their synthetic simplicity and use of readily available reagents. Vinylborates, vinyl halides, alkenyl acetates, and cyclic 1,3-dicarbonyls have been known for the direct alkenylation of arene and (hetero)arene C H bonds. In a more simple and synthetically useful alkenylation, terminal alkenes have been applied as the coupling partners. However, little attention has been paid to the direct alkenylation of alkenyl C H bonds with an alkene as the coupling partner using C H bond activation. 1,3-Butadienes, as a class of versatile organic synthetic reagents, have usually been prepared by indirect methods. To date, only two reports have been documented for their direct synthesis, involving coupling two simple terminal alkenes, owing to the difficulty in activating two alkene substrates at the same time (Scheme 1). Although two examples involving the reaction of 3-methyl-1H-indenes with tert-butyl acrylate were also reported, no work has been directed to the direct alkenylation of open-chain internal alkenes with another alkene as the coupling partner. In order to realize the direct cross-coupling of an internal alkene with a terminal alkene, the low reactivity of an internal alkenyl C H bond should be overcome. We envisioned the introduction of a structural element that could increase the reactivity of an internal alkenyl C H bond. Thus, we hypothesized that a 1,2-dithiane group at the terminal position of an alkene should satisfy the requirement on activating an internal alkenyl C H bond, and a-oxoketene dithioacetals were chosen as the internal alkenes. Herein, we report the palladium(II)-catalyzed direct cross-coupling of a-oxoketene dithioacetals with terminal alkenes as well as the synthesis of bicyclic pyridones [Eq. (1)].

Lewis Acid-Catalyzed, Copper(II)-Mediated Synthesis of Heteroaryl Thioethers under Base-Free Conditions

A Lewis acid (Ag(I), Ni(II), or Fe(II)) catalyzed, Cu(II)-mediated thiolation reaction between heteroarenes and thiols was achieved with good yield under base-free conditions. DMSO could serve as an effective methylthiolation reagent for the synthesis of heterocyclic methyl thioethers.

C-Alkylation of Ketones and Related Compounds by Alcohols: Transition-Metal-Catalyzed Dehydrogenation.

Transition-metal-catalyzed C-alkylation of ketones and secondary alcohols, with alcohols, avoids use of organometallic or environmentally unfriendly alkylating agents by means of borrowing hydrogen (BH) or hydrogen autotransfer (HA) activation of the alcohol substrates. Water is formed as the only by-product, thus making the BH process atom-economical and environmentally benign. Diverse homogeneous and heterogeneous transition-metal catalysts, ketones, and alcohols can be used for this transformation, thus rendering the BH process promising for replacing those procedures that use traditional alkylating agents. This Minireview summarizes the advances during the last five years in transition-metal-catalyzed BH α-alkylation of ketones, and β-alkylation of secondary alcohols with alcohols. A discussion on the application of the BH strategy for C-C bond formation is included.

Brønsted Acid Activation Strategy in Transition‐Metal Catalyzed Asymmetric Hydrogenation of N‐Unprotected Imines, Enamines, and N‐Heteroaromatic Compounds

Asymmetric hydrogenation plays an important role in organic synthesis, but that of the challenging substrates such as N-unprotected imines, enamines, and N-heteroaromatic compounds (1H-indoles, 1H-pyrroles, pyridines, quinolines, and quinoxalines) has only received increased attention in the past three years. Considering the interaction modes of a Brønsted acid with a Lewis base, Brønsted acids may be used as the ideal activators of C=N bonds. This Minireview summarizes the recent advances in transition-metal-catalyzed, Brønsted acid activated asymmetric hydrogenation of these challenging substrates, thus offering a promising substrate activation strategy for transformations involving C=N bonds.

Pt-Sn/γ-Al2O3-catalyzed highly efficient direct synthesis of secondary and tertiary amines and imines.

Versatile syntheses of secondary and tertiary amines by highly efficient direct N-alkylation of primary and secondary amines with alcohols or by deaminative self-coupling of primary amines have been successfully realized by means of a heterogeneous bimetallic Pt-Sn/γ-Al(2)O(3) catalyst (0.5 wt % Pt, Pt/Sn molar ratio=1:3) through a borrowing-hydrogen strategy. In the presence of oxygen, imines were also efficiently prepared from the tandem reactions of amines with alcohols or between two primary amines. The proposed mechanism reveals that an alcohol or amine substrate is initially dehydrogenated to an aldehyde/ketone or NH-imine with concomitant formation of a [PtSn] hydride. Condensation of the aldehyde/ketone species or deamination of the NH-imine intermediate with another molecule of amine forms an N-substituted imine which is then reduced to a new amine product by the in-situ generated [PtSn] hydride under a nitrogen atmosphere or remains unchanged as the final product under an oxygen atmosphere. The Pt-Sn/γ-Al(2)O(3) catalyst can be easily recycled without Pt metal leaching and has exhibited very high catalytic activity toward a wide range of amine and alcohol substrates, which suggests potential for application in the direct production of secondary and tertiary amines and N-substituted imines.

Efficient Rh(I)-Catalyzed Direct Arylation and Alkenylation of Arene C−H Bonds via Decarbonylation of Benzoic and Cinnamic Anhydrides

Efficient rhodium(I)-catalyzed regioselective direct arylation and alkenylation of aromatic C-H bonds has been realized with aromatic carboxylic and cinnamic anhydrides as the coupling partners via decarbonylation and C-H activation under phosphine-free conditions.

Hydrogenation of nitroaromatics by polymer-anchored bimetallic palladium-ruthenium and palladium-platinum catalysts under mild conditions

Abstract Polymer-achored monometallic palladium catalyst PVP-PdCl2 (PVP = poly(N-vinyl-2-pyrrolidone)) exhibits very high activity for the hydrogenation of p-chloronitrobenzene (CNB) to aniline (AN) in the presence of base at 65°C and atmospheric pressure. In this case, the substrate is rapidly hydrodechlorinated to nitrobenzene (NB) which is then reduced to AN. Using the polymer-anchored bimetallic palladium-ruthenium catalyst, PVP-PdCl2-RuCl3, and in the presence of 1.0 mol% of sodium acetate, a strong synergic effect gives rise to a remarkable increase of the selectivity for p-chloroaniline (CAN) and the maximum selectivity of CAN is up to 94%. For the hydrogenation of the non-halo-substituted nitroaromatics to the corresponding aromatic amines, the monometallic PVP-PdCl2 catalyst only shows mild or poor activity, but the colloidal polymer-anchored bimetallic palladium-platinum catalyst, PVP-Pd-1 4Pt , exhibits very high activity and selectivity.

Highly Active Ruthenium(II) Complex Catalysts Bearing an Unsymmetrical NNN Ligand in the (Asymmetric) Transfer Hydrogenation of Ketones

N-Heterocylic ligands have recently become more and more attractive in homogeneous catalysis and organic synthesis because their organometallic complexes usually exhibit higher reactivity and better stability than those with phosphine ligands. Tridentate NNN ligands such as Pybox, 2,6-bis ACHTUNGTRENNUNG(imino)pyridines,[3] terpyridines, and other symmetrical NNN ligands have demonstrated their potential applications. However, examples of unsymmetrical tridentate NNN ligands and their transition-metal complexes are scarce. Transition-metal complexes bearing an unsymmetrical polydentate ligand are usually bestowed with good catalytic activity. Thus, unsymmetrical pyridyl-based NNN ligands are strongly desired for the construction of highly active transition-metal complex catalysts. Functional metal complexes were obtained with symmetrical bis(benzimidazol-2-yl)pyridines and bis(N-alkylbenzimidazol-2-yl)pyridines, and the electronic properties of the respective ruthenium complexes have been described. However, only a few of them have been applied as catalysts. We recently synthesized very efficient Ru pyridyl–pyrazolyl-based NNN complex catalysts for transfer hydrogenation of ketones. Ru-catalyzed transfer hydrogenation reactions with 2-propanol as the hydrogen source have been extensively studied by Noyori et al. Baratta’s group recently reported highly active Ru 2-(aminomethyl)pyridinylphosphane complex catalysts for the transfer hydrogenation of ketones. A few Ru complex catalysts featuring no N H functionality have also been documented for the same purpose. Herein, we report the construction of unsymmetrical (chiral) pyridyl– benzimidazolyl-based NNN ligands and their Ru complex catalysts for the (asymmetric) transfer hydrogenation of ketones by following the strategy shown in Scheme 1. The mono-N-alkyl derivative of bis(benzimidazol-2-yl)pyridine (1), that is, 2, and bis(N-propylbenzimidazol-2yl)pyridine (3) were obtained by reacting 1 with 1-bromopropane in the presence of NaH (Scheme 2). Reactions of ligands 1–3 with one equivalent of [Ru ACHTUNGTRENNUNG(PPh)3Cl2] in refluxing methanol afforded Ru complexes 4–6 in 76–91 % yields. Treatment of 5 with K2CO3 base in CH2Cl2 formed

Copper-Catalyzed Oxidative Arylation of Heteroarenes under Mild Conditions Using Dioxygen as the Sole Oxidant

Arylation of heteroarene has been intensively studied over the past few years because aryl-substituted aromatic heterocycles are known to exhibit interesting biological activities and are also useful as electronic materials. Numerous methods have been reported to successfully construct this motif by transition-metal-catalyzed cross-coupling and most of them required expensive transition-metal catalysts such as Rh and Pd. It is ideal to replace these catalysts by cheap metals. In 2007, Daugulis and co-workers first reported a copper-catalyzed cross-coupling of heteroarenes and aryl iodide under high temperature. You and co-workers modified a prior reported method by using aryl bromide as the electrophile; however, the reaction needed to be kept at high temperature for at least for one day. Very recently, Miura and Itami reported the Ni-catalyzed cross-coupling between heteroarenes and aryl halide, respectively. Their protocols also suffered from harsh conditions; for example, high temperatures and long reaction times. Therefore, finding a more practical and efficient method to achieve this aim remains a challenge. Like the traditional transition-metal-catalyzed cross-coupling reactions, previously reported catalytic methods for arylation of heteroarenes normally worked between heteroarene nucleophiles and aryl halide electrophiles (Scheme 1, A). Recently, remarkable progress has been made in oxidative cross-coupling. Unlike the traditional cross-coupling reactions, the oxidative cross-coupling needs two nucleophilic partners in the reaction and the transformation includes three steps: a two-stage transmetalation to high-valent metal catalyst, reductive elimination, then reoxidation of the catalyst to high valency by the external oxidant. The terminal oxidant that serves in oxidative cross-coupling always involves metal salts, organohalide, or benzoquinone, and so on. Replacement of these oxidants by dioxygen is more practical and more economical since this oxidant is very cheap and produces no environmentally hazardous byproduct. The C-2 position of azole or thiazole is easily deprotonated under basic conditions. It may serve as a nucleophile and cross-couple with another nucleophile under oxidative coupling conditions (Scheme 1, B). Recently, Su and coworkers reported the Cu-catalyzed oxidative amination of azoles and thiazoles by using O2 as the oxidant. [6] Only a few examples have been reported on oxidative arylation of azoles and thiazoles. Miura and co-workers developed an oxidative arylation and alkenylation of heteroarenes including azole and thiazole with organosilicon reagents by a nickel catalyst. You reported a Pd-catalyzed oxidative cross-coupling reaction between heteroarenes and aryl boronic acid. Both of them require metal salts and/or benzoquinone as oxidant. Very recently, Pdand Ni-catalyzed oxidative arylation of azoles and thiazoles with aryl boronic acid by using dioxygen as oxidant have been achieved. The reactions also proceeded under high temperature and/or for a long reaction time. All above mentioned drawbacks have made the prior methods less attractive. In our study, we found that CuCl could very efficiently catalyze the oxidative cross-coupling between heteroarenes and arylboronic esters with good yields and selectivities. This reaction was complete in only minutes under mild conditions by using dioxygen as the sole oxidant. We initiated our investigation by using Pd as the catalyst and dioxygen as the oxidant (Table 1, entry 1). Under variant conditions, only low yields were obtained (details are shown in the Supporting Information). We then switched [a] F. Yang, Prof. Z. Xu, Z. Wang, Prof. Z. K. Yu Dalian Institute of Chemical Physics Chinese Academy of Sciences Dalian 116023 (P.R. China) Fax: (+86)411-84379227 E-mail : xuzq@dicp.ac.cn zkyu@dicp.ac.cn [b] F. Yang, Z. Wang, Prof. R. Wang Key Laboratory of Preclinical Study for New Drugs of Gansu Province Department Institute of Biochemistry and Molecular Biology Lanzhou University, Lanzhou 730000 (P.R. China) Fax: (+86)931-8911255 E-mail : wangrui@lzu.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201100136. Scheme 1. Two pathways for the arylation of heteroarene.