Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the area of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach that has seen widespread success involves the use of a proximal heteroatom that serves as a directing group for the selective functionalization of a specific C-H bond. In a survey of examples of heteroatom-directed Rh catalysis, two mechanistically distinct reaction pathways are revealed. In one case, the heteroatom acts as a chelator to bind the Rh catalyst, facilitating reactivity at a proximal site. In this case, the formation of a five-membered metallacycle provides a favorable driving force in inducing reactivity at the desired location. In the other case, the heteroatom initially coordinates the Rh catalyst and then acts to stabilize the formation of a metal-carbon bond at a proximal site. A true test of the utility of a synthetic method is in its application to the synthesis of natural products or complex molecules. Several groups have demonstrated the applicability of C-H bond functionalization reactions towards complex molecule synthesis. Target-oriented synthesis provides a platform to test the effectiveness of a method in unique chemical and steric environments. In this respect, Rh-catalyzed methods for C-H bond functionalization stand out, with several syntheses being described in the literature that utilize C-H bond functionalization in a key step. These syntheses are highlighted following the discussion of the method they employ.

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Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

N-Heterocyclic Carbenes in Late Transition Metal Catalysis

The area of transition-metal-catalyzed direct arylation through cleavage of CH bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross-coupling reactions with organometallic reagents In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners—including electrophilic aryl chlorides and tosylates as well as simple arenes in cross-dehydrogenative arylations Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations

Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage.

Ruthenium(II)-Catalyzed C–H Bond Activation and Functionalization

Let's make 'meri': Metal-free direct alkenylation of indoles was realized by acid-mediated substitution reactions of α-oxo ketene dithioacetals with indoles in trifluoroacetic acid/dichloromethane, selectively affording β-indolyl mono- and disubstituted α,β-unsaturated carbonyl compounds (see scheme). Condensation of the indolyl/ketene monothioacetals and guanidine nitrate efficiently produced meridianin derivatives.

Direct Alkenylation of Indoles with α‐Oxo Ketene Dithioacetals: Efficient Synthesis of Indole Alkaloids Meridianin Derivatives.

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.

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

Highly functionalized pyrrolone derivatives, e.g. (VII) and (IX) are accessible via tuneable C—S and C—Cl bond cleavage.

Copper‐Mediated Intramolecular Oxidative C—H/N—H Cross‐Coupling of α‐Alkenoyl Ketene N,S‐Acetals to Synthesize Pyrrolone Derivatives.

Fe-catalyzed treatment of a number of 2-substituted indoles with arylacetaldehydes results in efficient formation of 3-alkenylated indoles.

FeCl3·6H2O-Catalyzed Alkenylation of Indoles with Aldehydes.

A method for preparing benzyl selenium ether, comprising putting the aromatic aldchyde, selenium and water into the organic dissolvent, ventilating carbon monoxide into the dissolvent, stirring at the temperature of 50-100 DEG C for 5-15 hours; cooling to normal temperature, extracting with ether, removing the solvent in the tobacco extract in reduced pressure and getting the product. The substituent R of aromatic aldchyde can be a kind of or multiple kinds of electron donating groups and/or electron-attacting groups or hydrogen atom; the consumption between aromatic aldchyde and selenium is 1:1~1.5 in moles, the consumption between aromatic aldchyde and water is 1:1~1:100 in moles, the consumption between reactant and solvent is 1:1~1:500 in moles; the velocity of carbon monoxide bubbling is 20~60 ml/min. The process is simple and being carried out in the same reactor under normal pressure, and gets a high yield.

Zhengkun Yu

Papers

Direct Alkenylation of Indoles with α‐Oxo Ketene Dithioacetals: Efficient Synthesis of Indole Alkaloids Meridianin Derivatives.

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

Copper‐Mediated Intramolecular Oxidative C—H/N—H Cross‐Coupling of α‐Alkenoyl Ketene N,S‐Acetals to Synthesize Pyrrolone Derivatives.

FeCl3·6H2O-Catalyzed Alkenylation of Indoles with Aldehydes.

Method for synthesizing dibenzyl diselenide