Da-Gang Yu

An efficient organocatalytic method for constructing biaryls through aromatic C–H activation

The direct functionalization of C–H bonds has drawn the attention of chemists for almost a century. C–H activation has mainly been achieved through four metal-mediated pathways: oxidative addition, electrophilic substitution, σ-bond metathesis and metal-associated carbene/nitrene/oxo insertion. However, the identification of methods that do not require transition-metal catalysts is important because methods involving such catalysts are often expensive. Another advantage would be that the requirement to remove metallic impurities from products could be avoided, an important issue in the synthesis of pharmaceutical compounds. Here, we describe the identification of a cross-coupling between aryl iodides/bromides and the C–H bonds of arenes that is mediated solely by the presence of 1,10-phenanthroline as catalyst in the presence of KOt-Bu as a base. This apparently transition-metal-free process provides a new strategy with which to achieve direct C–H functionalization. C–H activation has usually been achieved by transition metal-mediated pathways. Here, a cross-coupling between aryl halides and common arenes mediated by 1,10-phenanthroline as catalyst, in the presence of potassium tert-butoxide as base is described. Such reactions open a new window for achieving C–H activation without the need for transition metal catalysts.

Co(III)-Catalyzed C–H Activation/Formal SN-Type Reactions: Selective and Efficient Cyanation, Halogenation, and Allylation

The first cobalt-catalyzed cyanation, halogenation, and allylation via C-H activation have been realized. These formal SN-type reactions generate valuable (hetero)aryl/alkenyl nitriles, iodides, and bromides as well as allylated indoles using a bench-stable Co(III) catalyst. High regio- and mono-selectivity were achieved for these reactions. Additionally, allylation proceeded efficiently with a turnover number of 2200 at room temperature, which is unprecedented for this Co(III) catalyst. Alkenyl substrates and amides have been successfully utilized in Cp*Co(III)-catalyzed C-H activation for the first time.

Activation of "Inert" Alkenyl/Aryl CO Bond and Its Application in Cross-Coupling Reactions

Enol and phenol functionalities are very common in organic molecules. Utilization of these materials is very appealing in organic synthesis because they are important alternatives to organohalides in cross-coupling reactions. In this review, we summarize the transition-metal-catalyzed cross-coupling of enol- and phenol-based electrophiles, including phosphates, sulfonates, ethers, carboxylates, and phenolates.

Biaryl Construction via Ni-Catalyzed C-O Activation of Phenolic Carboxylates

Biaryl scaffolds were constructed via Ni-catalyzed aryl C-O activation by avoiding cleavage of the more reactive acyl C-O bond of aryl carboxylates. Now aryl esters, in general, can be successfully employed in cross-coupling reactions for the first time. The substrate scope and synthetic utility of the chemistry were demonstrated by the syntheses of more than 40 biaryls and by constructing complex organic molecules. Water was observed to play an important role in facilitating this transformation.

RhIII/CuII-Cocatalyzed Synthesis of 1H-Indazoles through C–H Amidation and N–N Bond Formation

Substituted 1H-indazoles can be formed from readily available arylimidates and organo azides by Rh(III)-catalyzed C-H activation/C-N bond formation and Cu-catalyzed N-N bond formation. For the first time the N-H-imidates are demonstrated to be good directing groups in C-H activation, also capable of undergoing intramolecular N-N bond formation. The process is scalable and green, with O2 as the terminal oxidant and N2 and H2O formed as byproducts. Moreover, the products could be transformed to diverse important derivatives.

Cobalt(III)-Catalyzed Directed C-H Allylation.

The cobalt(III)-catalyzed allylation was developed for amide-directed C-H activation of arenes, heteroarenes, and olefins. A variety of allyl sources can be employed to introduce this useful functional group.

Direct Application of Phenolic Salts to Nickel‐Catalyzed Cross‐Coupling Reactions with Aryl Grignard Reagents

nickel D . -G . YU , B . J . L I , S . F. Z H E N G , B . T. G U A N , B . -Q . WA N G , Z . J . S H I * ( P E K IN G U N IVE R S I T Y, BE I J I N G , S T A T E KEY L A B O R A T O R Y O F O RG A N O M E T A L L I C C H E M I S T R Y, S H A N G H A I A N D S I C H U A N N O R M A L U N IVE R S IT Y, CH E N G D U , P. R . O F C H I N A ) Direct Application of Phenolic Salts to Nickel-Catalyzed Cross-Coupling Reactions with Aryl Grignard Reagents Angew. Chem. Int. Ed. 2010, 49, 4566-4570.

Mutual Activation: Suzuki–Miyaura Coupling through Direct Cleavage of the sp2 CO Bond of Naphtholate

Since the 1970s, the development of various cross-coupling reactions that start from organohalides has provided efficient methods to build up biaryl compounds, which are important structures in bioactive compounds, natural products, and synthetic materials. Cross-coupling reactions were recognized last year with the Nobel Prize, and owing to the mild reaction conditions, high functional-group tolerance, and the wide commercial availability of nontoxic and stable boronic acid derivatives, the Suzuki–Miyaura reaction is particularly attractive among the various cross-coupling reactions. The Suzuki–Miyaura coupling is now successful both under homogeneous and heterogeneous catalysis, and has been widely applied to the synthesis of important drugs, polymers, and materials in both academic and industrial laboratories. Investigations offer excellent chances to use simple arenes in many cross-coupling reactions. However, the lack of accuracy obtained using a directing strategy, indicates that aryl halides are currently not replaceable. Owing to the abundance and availability of phenol derivatives, many methods to activate phenols so that they could take the place of halides in these reactions have been tested. Herein, we report the new concept of mutual activation of the C O bond in phenols and the C B bond in aryl boronic acid derivatives to realize the Suzuki–Miyaura coupling of phenols. Recent advances have made less-reactive aryl ethers, carboxylic esters, and carbamates applicable in Suzuki– Miyaura coupling reactions. Undoubtedly, the use of phenols in the Suzuki–Miyaura coupling would be optimal in terms of meeting the requirements of sustainable chemistry: not only improving step economy and atom economy and starting from naturally available chemicals, but also producing no carbon-containing by-products. Although the recent success in the Kumada–Tamao–Corriu coupling using phenolates with active Grignard reagents provided a potential solution, the challenge to cross-couple phenols and their salts with much less-reactive species, for example, aryl boronic acids, still presents difficulties. Our recent efforts have turned to the development of an efficient method for the application of phenolates in the Suzuki–Miyaura coupling reaction. In a traditional Suzuki–Miyaura coupling, the hydroxy group of the phenol species is derivatized to form active compounds. Meanwhile, the formation of the borate facilitates the transmetalation in the catalytic cycle (Scheme 1A and B). In our novel design, the phenolate could react with the three-coordinate aryl boronic reagents to generate aryl borates. In these complexes, the borate might activate the aryl C O bond and the borate anion might play the same role as a derivatized hydroxy group, such as a sulfonate and phosphate. Meanwhile, the formation of the borate activates the C B bond and promotes the transmetalation later in the reaction cycle (Scheme 1C). The advantage is that both the coupling partners come from the same in situ generated aryl borate, and the aryl C O bond and the aryl C B bond are mutually activated. Notably the two partners activate each other and so avoid the need for preactivation of the phenol species and the addition of extra base (Scheme 1B).

Pd-catalyzed C-H functionalizations of O-methyl oximes with arylboronic acids.

Useful methods have been developed to construct ortho-arylated aryl aldoximes, aryl ketoximes, and fluorenones via Pd(II)-catalyzed direct C-H arylation by using arylboronic acids as arylating reagents based on the analysis of the pathways of direct functionalization of aryl aldoximes.

α-MsO/TsO/Cl Ketones as Oxidized Alkyne Equivalents: Redox-Neutral Rhodium(III)-Catalyzed CH Activation for the Synthesis of N-Heterocycles†

α-Halo and pseudohalo ketones are used for the first time as C(sp(3))-based electrophiles in transition-metal-catalyzed C-H activation and as oxidized alkyne equivalents in Rh(III)-catalyzed redox-neutral annulations to generate diverse N-heterocycles. This transformation is efficient and scalable. Due to the mild reaction conditions, a variety of functional groups could be tolerated.