Weiping Su

Recent advances in directed C–H functionalizations using monodentate nitrogen-based directing groups

The use of directing groups has proven to be a successful strategy to enhance reactivity and control selectivity in C–H functionalization reactions. In the past decade, a multitude of new transformations and new directing groups have been explored, and several recent reviews have discussed directing group approaches for C–H functionalization. This review focuses specifically on the use of monodentate nitrogen-based directing groups published during the past two years, with the aim of covering a body of literature that is complementary to existing reviews.

Pd(OAc)(2)-Catalyzed Oxidative C-H/C-H Cross-Coupling of Electron-Deficient Polyfluoroarenes with Simple Arenes

Pd(OAc)(2)-catalyzed intermolecular C-H/C-H cross-coupling reactions between electron-deficient polyfluoroarenes and simple arenes for the synthesis of fluorinated biaryls have been developed. Deuterium-labeling experiments suggested that C-H bond cleavage of the simple arenes rather than the polyfluoroarenes is involved in the rate-limiting step.

Copper-catalyzed direct alkynylation of electron-deficient polyfluoroarenes with terminal alkynes using O2 as an oxidant.

A copper-catalyzed direct alkynylation of electron-deficient polyfluoroarenes with a wide range of terminal alkynes is realized for the first time. The reaction proceeds under mild conditions with O(2) as an oxidant.

Palladium-Catalyzed Decarboxylative CH Bond Arylation of Thiophenes†

Conventionally, 2-arylthiophenes are synthesized by cross-coupling reactions of (hetero)aryl halides with (hetero)aryl organometallic reagents. Owing to the wide applications of this family of compounds, the development of new methods for the synthesis of valuable 2-arylthiophenes from simple and readily available starting materials by concise steps continues to be a target of intense interest. In this context, the direct C H arylation of thiophenes with aryl iodides and bromides has been achieved by using Pd, Ir, Rh, and Cu catalysts; thus thiophenes were directly used to replace expensive thienyl organometallic reagents in traditional cross-coupling reactions. As a highly efficient approach to 2-arylthiophenes, the oxidative cross-coupling of two unfunctionalized arenes has been realized in the palladium-catalyzed reactions of thiophenes with C H acidic polyfluoroarenes and nitrogen-containing heteroarenes. Moreover, metal-free oxidative cross-couplings of thiophenes with electron-rich arenes has also been reported. Although these transformations represent substantial progress toward the syntheses of 2-arylthiophenes in an atom-economical and environmentally benign way, there is significant room for improvement with respect to the generality and functionalgroup tolerance of these state-of-the-art methods. On the other hand, the use of carboxylic acids as crosscoupling components by a metal-promoted decarboxylation process is a rapidly growing area of research because of their low cost, diversity, and ready availability. Recently, decarboxylative cross-coupling reactions have been expanded to decarboxylative C H bond functionalization, including intramolecular reactions for the syntheses of dibenzofurans, intermolecular reactions for the selective arylation of indoles, ortho acylation of acetanilides, the construction of azole–azole linkages, and the direct arylation of C H acidic polyfluorobenzenes. A decarboxylative C H bond functionalization that combines two newly emerging approaches, that is, decarboxylation and direct C H bond functionalization, offers a new synthetic strategy in synthesis. However, the challenges posed by this promising process remain. For example, many of the decarboxylative C H bond functionalization reactions were restricted to a narrow range of arene carboxylic acids because the reactivity of the arene carboxylic acids toward decarboxylation is very sensitive to the substitutents on benzene rings. Herein, we report the decarboxylative C H bond arylation of thiophenes catalyzed by a Pd(OAc)2/Ag2CO3 system; electron-rich, electron-deficient, and heterocyclic benzoic acids can all be used as aryl sources in this reaction and a broad spectrum of functional groups can be tolerated. As generally proposed for similar processes, the Pd/Agcatalyzed decarboxylative C H arylation of thiophenes may involve a Pd-promoted C H cleavage to form a palladium intermediate, a Ag-promoted decarboxylation to generate an aryl silver species, a subsequent aryl transfer from Ag to Pd, and reductive elimination (Scheme 2). In light of this proposal, we envisioned that the major problems impeding the execution of the target process would result from the following side reactions: 1) the unstable aryl silver intermediate is liable to protodecarboxylation and decarboxylative homocoupling if the desired cross-coupling reaction Scheme 1. Three examples illustrating the importance of compounds containing a 2-arylthiophene moiety: A natural product (A); Evista (B), a medicine used to prevent and treat osteoporosis; ITPEEPT (C), an electrochromic device.

Pd(O2CCF3)2/Benzoquinone: A Versatile Catalyst System for the Decarboxylative Olefination of Arene Carboxylic Acids

A versatile palladium catalyst system was developed to effect the decarboxylative Heck coupling of a variety of arenecarboxylic acids with a wide range of olefins. The key to obtaining the efficient catalyst system is the use of 1-adamatanecarboxylic acid as additive. Alkyl-substituted olefins with coordinating groups were observed to provide significantly improved regioselectivity compared with other alkyl-substituted olefins lacking coordinating groups, and the acetate group of allylic ester was also tolerated in this reaction.

Mild and Selective Ru-Catalyzed Formylation and Fe-Catalyzed Acylation of Free (N–H) Indoles Using Anilines as the Carbonyl Source

C3-selective formylation and acylation of free (N-H) indoles under mild conditions can be achieved by using Ru- and Fe-catalyzed oxidative coupling of free (N-H) indoles with anilines, respectively. Both processes are operationally simple, compatible with a variety of functional groups and generally provide the desired products in good yields. (13)C-labeling experiments unambiguously established that the carbonylic carbon in the formylation products originated from methyl group of N-methyl aniline.

Pd-Catalyzed Dearboxylative Heck Coupling with Dioxygen as the Terminal Oxidant

A Pd-catalyzed desulfitative Heck-type reaction of aromatic sulfinic acid sodium salts with various olefins is developed with O(2) as the terminal oxidant under mild conditions. The presence of phosphane ligand DPEphos in anisole can significantly enhance the reaction selectivity.

Carboxylic Acids as Traceless Directing Groups for the Rhodium(III)-Catalyzed Decarboxylative CH Arylation of Thiophenes†

A rhodium(III)-catalyzed carboxylic acid directed decarboxylative C-H/C-H cross-coupling of carboxylic acids with thiophenes has been developed. With a slight adjustment of the reaction conditions based on the nature of the substrates, aryl carboxylic acids with a variety of substituents could serve as suitable coupling partners, and a broad variety of functional groups were tolerated. This method provides straightforward access to biaryl scaffolds with diverse substitution patterns, many of which have conventionally been synthesized through lengthy synthetic sequences. An illustrative example is the one-step gram-scale synthesis of a biologically active 3,5-substituted 2-arylthiophene by way of the current method.

Pd/PR3-catalyzed cross-coupling of aromatic carboxylic acids with electron-deficient polyfluoroarenes via combination of decarboxylation with sp2 C-H cleavage.

By using Pd(TFA)(2)/PCy(3) as a catalyst, a broad range of aromatic carboxylic acids, including heteroaromatic carboxylic acids, efficiently underwent decarboxylative coupling with an array of polyfluoroarenes in the presence of stoichiometric amount of silver salts to generate biaryls. Silver salts were adjusted to the reactivity of aromatic carboxylic acids to efficiently suppress the protodecarboxylation and therefore improve decarboxylative cross-couplings. It was established that the palladium complex containing the PCy(3) ligand was capable of catalyzing the decarboxylation of electron-rich aromatic carboxylic acids, and silver salts promoted the decarboxylation of both electron-rich and -deficient ones. To explain the two different decarboxylation processes, two possible reaction pathways are proposed, which were further supported by the facts that the stoichiometric arylpalladium complex can directly arylate pentafluorobenzene in the presence of PCy(3) and the arylpalladium complex can catalyze the decarboxylative coupling of 2,4-dimethoxybenzoic acid with pentafluorobenzene. The kinetic isotope effect of 4.0 clearly showed that the C-H bond cleavage of polyfluoroarenes is involved in the rate-determining step.

Palladium-catalyzed direct arylation of electron-deficient polyfluoroarenes with arylboronic acids.

The palladium-catalyzed direct arylation of electron-deficient arenes that contain two or more fluorine groups with arylboronic acids was realized. The key to achieving a broad substrate scope with respect to both polyfluorobenzenes and arylboronic acids is the choice of bases depending on acidities of polyfluorobenzenes.