Transition-metal-catalyzed cross-coupling reactions have been well-established as indispensable tools in modern organic synthesis. One of the major research goals in cross-coupling area is expanding the scope of the coupling partners. In the past decade, diazo compounds (or their precursors N-tosylhydrazones) have emerged as nucleophilic cross-coupling partners in C–C single bond or C═C double bond formations in transition-metal-catalyzed reactions. This type of coupling reaction involves the following general steps. First, the organometallic species is generated by various processes, including oxidative addition, transmetalation, cyclization, C–C bond cleavage, and C–H bond activation. Subsequently, the organometallic species reacts with the diazo substrate to generate metal carbene intermediate, which undergoes rapid migratory insertion to form a C–C bond. The new organometallic species generated from migratory insertion may undergo various transformations. This type of carbene-based coupling has proven...

Transition-Metal-Catalyzed Cross-Couplings through Carbene Migratory Insertion

The development of new methods for the direct functionalization of unactivated C–H bonds is ushering in a paradigm shift in the field of retrosynthetic analysis. In particular, the catalytic enantioselective functionalization of C–H bonds represents a highly atom- and step-economic approach toward the generation of structural complexity. However, as a result of their ubiquity and low reactivity, controlling both the chemo- and stereoselectivity of such processes constitutes a significant challenge. Herein we comprehensively review all asymmetric transition-metal-catalyzed methodologies that are believed to proceed via an inner-sphere-type mechanism, with an emphasis on the nature of stereochemistry generation. Our analysis serves to document the considerable and rapid progress within in the field, while also highlighting limitations of current methods.

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Catalytic Enantioselective Transformations Involving C-H Bond Cleavage by Transition-Metal Complexes.

Transition-metal-catalyzed activation of C–H and C–C bonds is a challenging area in synthetic organic chemistry. Among various methods to accomplish these processes, the approach using metal–organic cooperative catalytic systems is one of the most promising. In this protocol, organic molecules as well as transition metals act as catalysts to bring about reactions, which proceed with high efficiencies and selectivities. Various metal–organic cooperative catalytic systems developed for C–H and C–C bond activation reactions are discussed in this review. Also discussed are how each metal–organic cooperative catalyst affects the reaction mechanism and what kinds of substrates can be applied in each of the catalytic processes.

Metal–Organic Cooperative Catalysis in C–H and C–C Bond Activation

ConspectusDirect C–H bond activation is an important reaction in synthetic organic chemistry. This methodology has the potential to simplify reactions by avoiding the use of prefunctionalized reagents. However, selectivity, especially site selectivity, remains challenging. Sequential reactions, in which different molecules or groups are combined in an ordered sequence, represent a powerful tool for the construction of complex molecules in a single operation.We have discovered and developed a synthetic methodology that combines selective C–H bond activation with sequential reactions. This procedure, which is now known as the “Catellani reaction”, enables the selective functionalization of both the ortho and ipso positions of aryl halides. The desired molecules are obtained with high selectivity from a pool of simple precursors. These molecules are assembled under the control of a palladacycle, which is formed through the joint action of a metal (Pd) and an olefin such as norbornene. These two species act c...

Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C-H Bond Activation.

The Catellani reaction--a palladium-catalysed C-H functionalization reaction mediated by norbornene--was first reported in 1997. The capacity to functionalize both the ortho and ipso positions of aryl halides in a single transformation held great appeal. We reported an annulative Catellani reaction in 2000. Since then, our two groups have explored the synthetic utility of this reaction and dramatic progress has been made by a number of groups in the past five years. Whereas the original Catellani reaction uses Pd(0) catalysts, recent studies have shown that Pd(II) catalysts can be used in combination with norbornene to effect (1) direct 2-alkylation of indoles and pyrroles and (2) selective meta-C-H functionalization of arenes bearing commonly used ortho-directing groups, thereby opening new avenues for future research. We describe the most recent developments concerning the Pd-catalysed norbornene-mediated C-H functionalization of arenes, including applications in natural products synthesis. We outline challenges and future opportunities.

Palladium-catalysed norbornene-mediated C-H functionalization of arenes.

A palladium-catalyzed asymmetric synthesis of planar chiral metallocene compounds is reported. The reaction stereoselectively functionalized one of the ortho C-H bonds of Cp rings by intramolecular cyclization to form indenone derivatives in high yields with excellent enantioselectivity. The mild set of reaction conditions allowed a wide variety of chiral metallocene compounds to be synthesized with broad functional group tolerance. The influences of preinstalled chiralities on the other Cp-ring were also investigated.

Palladium-catalyzed intramolecular asymmetric C-H functionalization/cyclization reaction of metallocenes: an efficient approach toward the synthesis of planar chiral metallocene compounds.

A Pd-catalyzed chemoselective Catellani reaction of iodopyrroles was developed. The rare chemoselectivity between two different aryl halides was realized by optimizing the kinetics of the different steps of this multicomponent process. The new developed method led to the rapid synthesis of rhazinal in a highly efficient manner.

Pd-Catalyzed Chemoselective Catellani Ortho-Arylation of Iodopyrroles: Rapid Total Synthesis of Rhazinal

Pd-catalyzed Heck-type cascade reactions with N-tosyl hydrazones: an efficient way to alkenes via in situ generated alkylpalladium.

A palladium-catalyzed intramolecular asymmetric Cp–H functionalization/cyclization reaction to construct planar chiral quinilinoferrocenes was reported. The current investigation indicated that Carriera's O-PINAP ligands gave the best enantiomeric induction. The palladium-catalyzed reaction allowed a variety of chiral quinilinoferrocenes to be synthesized with broad functional group tolerance.

Xinna Ma

Papers

Palladium-catalyzed intramolecular asymmetric C-H functionalization/cyclization reaction of metallocenes: an efficient approach toward the synthesis of planar chiral metallocene compounds.

Pd-Catalyzed Chemoselective Catellani Ortho-Arylation of Iodopyrroles: Rapid Total Synthesis of Rhazinal

Pd-catalyzed Heck-type cascade reactions with N-tosyl hydrazones: an efficient way to alkenes via in situ generated alkylpalladium.

Palladium-catalyzed intramolecular Cp–H bond functionalization/arylation: an enantioselective approach to planar chiral quinilinoferrocenes

Pd-Catalyzed Chemoselective Catellani ortho-Arylation of Iodopyrroles: Rapid Total Synthesis of Rhazinal.