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.

Since their development in the 1970s, cross-coupling reactions catalyzed by transition metals have become one of the most important tools for constructing both carbon-carbon and carbon-heteroatom bonds. Traditionally, organohalides were widely studied and broadly used as the electrophile, both in the laboratory and in industry. Unfortunately, the high cost, environmental toxicity, and sluggish preparation often associated with aryl halides can make them undesirable for the large-scale syntheses of industrial applications. However, with the further development of catalytic systems, and particularly of the ligands contained therein, a variety of electrophiles have now been successfully applied to cross-coupling reactions. Oxygen-based electrophiles have attracted much attention due to their ready availability from phenol and carbonyl compounds. Initially, aryl and alkenyl triflates were used in cross-coupling reactions due to their high reactivity; however, low moisture stability and high cost hampered their application. Later, with the development of highly efficient catalytic systems, the less reactive sulfonates and phosphates were successfully employed in cross-coupling reactions. Although they have higher stability and can be easily prepared, low atom economy remains an obstacle to their broader utility. Our group has worked to directly apply the abundant and readily available oxygen-containing compounds, such as phenols, alcohols, ethers, and carbonyl compounds, to cross-coupling reactions. In this Account, we describe our recent efforts in transition-metal-catalyzed cross-coupling reactions of new O-based electrophiles via C-O bond activation. We began by developing the methylation of aryl methyl ethers and benzyl methyl ethers via Ni-catalyzed selective C-O bond cleavage. With the refined Ni-based catalytic system, we further applied aryl/alkenyl carboxylates and carbamates to Suzuki-Miyaura, Negishi, and Kumada-Tamao-Corriu reactions to construct various biaryl scaffolds and highly substituted alkenes. To further improve the carbon atom economy, we developed the diaryl sulfates as one-by-one electrophiles (that is, both aryl groups are used in the reaction). Most recently, we have achieved the first successful cross-coupling reaction of magnesium naphtholates with aryl Grignard reagents. These results extend aryl and benzyl ethers, aryl and alkenyl carboxylates/carbamates, and magnesium naphtholates as novel electrophiles in cross-coupling reactions. More importantly, these studies contribute to our better understanding the intrinsic nature of C-O bonds, which were traditionally considered "inert" but clearly show enormous synthetic potential with the proper catalysts.

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.

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.

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.

The first thiocarboxylation of styrenes and acrylates with CO was realized by using visible light as a driving force and catalytic iron salts as promoters. A variety of important β-thioacids were obtained in high yields. This multicomponent reaction proceeds in an atom- and redox-economical manner with broad substrate scope under mild reaction conditions. Notably, high regio-, chemo-, and diasteroselectivity are observed. Mechanistic studies indicate that a radical pathway can account for the unusual regioselectivity.

Metrics & MoreArticle Recommendations CONSPECTUS: Carbon dioxide (CO 2 ) is not only a greenhouse gas and a common waste product but also an inexpensive, readily available, and renewable carbon resource. It is an important one-carbon (C1) building block in organic synthesis for the construction of valuable compounds. However, its utilization is challenging owing to its thermodynamic stability and kinetic inertness. Although significant progress has been achieved, many limitations remain in this field with regard to the substrate scope, reaction system, and activation strategies. Since 2015, our group has focused on CO 2 utilization in organic synthesis. We are also interested in the vast possibilities of radical chemistry, although the high reactivity of radicals presents challenges in controlling selectivity. We hope to develop highly useful CO 2 transformations involving radicals by achieving a balance of reactivity and selectivity under mild reaction conditions. Over the past 6 years, we along with other experts have disclosed radical-type carboxylative cyclizations and carboxylations using CO 2 .We initiated our research by realizing the Cu-catalyzed radical-type oxytrifluoromethylation of allylamines and heteroaryl methylamines to generate valuable 2-oxazolidones with various radical precursors. Apart from Cu catalysis, visible-light photoredox catalysis is also a powerful method to achieve efficient carboxylative cyclization. In these cases, single-electron-oxidation-promoted C−O bond formation between benzylic radicals and carbamates is the key step. Since carboxylic acids exist widely in natural products and bioactive drugs and serve as important bulk chemicals in industry, we realized further visible-light-promoted carboxylations with CO 2 to construct such chemicals. We have achieved the selective umpolung carboxylations of imines, enamides, tetraalkylammonium salts, and oxime esters by successive single-electron-transfer (SSET) reduction. Using this strategy, we have also realized the dearomative arylcarboxylation of indoles with CO 2 . In addition to the incorporation of 1 equiv of CO 2 per substrate, we have recently developed a visible-light photoredox-catalyzed dicarboxylation of alkenes, allenes, and (hetero)arenes via SSET reduction, which allows the incorporation of two CO 2 molecules into organic compounds to generate valuable diacids as polymer precursors.In addition to the two-electron activation of CO 2 , we sought to develop new strategies to realize efficient and selective transformations via single-electron activation of CO 2 . Inspired by the hypothetical electron-transfer mechanism of iron−sulfur proteins, we have realized the visible-light-driven thiocarboxylation of alkenes with CO 2 using catalytic iron salts as promoters. The in-situ-generated Fe/S complexes are likely able to reduce CO 2 to its radical anion, which could react with alkenes to give a stabilized carbon radical. Moreover, we have also disclosed charge-transfer complex (CTC) formation between thiolate and acrylate/styr...

The reactivity and selectivity of 1,3-diynes in transition-metal-catalyzed CH activation is exploited to quickly assemble diverse polysubstituted bisheterocycles, which are highly important but difficult to access. By using the CH activation/1,3-diyne strategy, we overcame the challenges of selectivity (chemo-, regio-, and mono-/diannulation) and constructed seven kinds of adjacent bisheterocycles through the formation of four strategic bonds with high efficiency and high selectivity.