The direct functionalization of C-H bonds in organic compounds has recently emerged as a powerful and ideal method for the formation of carbon-carbon and carbon-heteroatom bonds. This Review provides an overview of C-H bond functionalization strategies for the rapid synthesis of biologically active compounds such as natural products and pharmaceutical targets.

C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals

Asymmetric enamine catalysis.

4.2.8. Reductive Coupling 3109 5. Reaction of Aromatic Compounds 3110 5.1. Electrophilic Substitutions 3110 5.2. Radical Substitution 3111 5.3. Oxidative Coupling 3111 5.4. Photochemical Reactions 3111 6. Reaction of Carbonyl Compounds 3111 6.1. Nucleophilic Additions 3111 6.1.1. Allylation 3111 6.1.2. Propargylation 3120 6.1.3. Benzylation 3121 6.1.4. Arylation/Vinylation 3121 6.1.5. Alkynylation 3121 6.1.6. Alkylation 3121 6.1.7. Reformatsky-Type Reaction 3122 6.1.8. Direct Aldol Reaction 3122 6.1.9. Mukaiyama Aldol Reaction 3124 6.1.10. Hydrogen Cyanide Addition 3125 6.2. Pinacol Coupling 3126 6.3. Wittig Reactions 3126 7. Reaction of R,â-Unsaturated Carbonyl Compounds 3127

Organic Reactions in Aqueous Media with a Focus on Carbon−Carbon Bond Formations: A Decade Update

The use of coordinating moieties as directing groups for the functionalization of aromatic CH bonds has become an established tool to enhance reactivity and induce regioselectivity. Nevertheless, with regard to the synthetic applicability of CH activation, there is a growing interest in transformations in which the directing group can be fully abandoned, thus allowing the direct functionalization of simple benzene derivatives. However, this approach requires the disclosure of new strategies to achieve reactivity and to control selectivity. In this review, recent advances in the emerging field of non-chelate-assisted CH activation are discussed, highlighting some of the most intriguing and inspiring examples of induction of reactivity and selectivity.

Beyond directing groups: transition-metal-catalyzed C-H activation of simple arenes.

C–H activation has surfaced as an increasingly powerful tool for molecular sciences, with notable applications to material sciences, crop protection, drug discovery, and pharmaceutical industries, among others. Despite major advances, the vast majority of these C–H functionalizations required precious 4d or 5d transition metal catalysts. Given the cost-effective and sustainable nature of earth-abundant first row transition metals, the development of less toxic, inexpensive 3d metal catalysts for C–H activation has gained considerable recent momentum as a significantly more environmentally-benign and economically-attractive alternative. Herein, we provide a comprehensive overview on first row transition metal catalysts for C–H activation until summer 2018.

3d Transition Metals for C-H Activation.

Pyrrolidine-thiourea as a bifunctional organocatalyst: highly enantioselective Michael addition of cyclohexanone to nitroolefins.

Pd-catalyzed C-3 selective olefination of pyridines is developed for the first time using 1,10-phenanthroline as the ligand. This finding provides a novel disconnection for the synthesis of pyridine-containing alkaloids and drug molecules as well as a new approach for developing Pd-catalyzed C-H functionalizations of pyridines.

Ligand-Promoted C-3 Selective C–H Olefination of Pyridines with Pd Catalysts

A Pd(II)-catalyzed C–H phosphorylation reaction has been developed using heterocycle-directed ortho-palladation. Both H-phosphonates and diaryl phosphine oxides are suitable coupling partners for this reaction.

Pd(II)-catalyzed phosphorylation of aryl C-H bonds.

The first example of Pd-catalyzed, C3-selective arylation of unprotected pyridines has been developed by employing a catalytic system consisting of Pd(OAc)(2) and 1,10-phenanthroline. This protocol provides an expeditious route to an important class of 3-arylpyridines and 3-arylpiperidines frequently found in bioactive compounds. A brief synthesis of the drug molecule (±)-preclamol is also reported.

Ligand-Promoted C3-Selective Arylation of Pyridines with Pd Catalysts: Gram-Scale Synthesis of (±)-Preclamol

Pseudo-C3-symmetric trisoxazoline copper(II) complexes prove to be excellent catalysts in the Friedel−Crafts alkylation of indoles with alkylidene malonates. The absolute stereochemistry of this re...

Controllable Enantioselective Friedel−Crafts Reaction1 between Indoles and Alkylidene Malonates Catalyzed by Pseudo-C3-Symmetric Trisoxazoline Copper(II) Complexes

Mengchun Ye

Papers

Pyrrolidine-thiourea as a bifunctional organocatalyst: highly enantioselective Michael addition of cyclohexanone to nitroolefins.

Ligand-Promoted C-3 Selective C–H Olefination of Pyridines with Pd Catalysts

Pd(II)-catalyzed phosphorylation of aryl C-H bonds.

Ligand-Promoted C3-Selective Arylation of Pyridines with Pd Catalysts: Gram-Scale Synthesis of (±)-Preclamol

Controllable Enantioselective Friedel−Crafts Reaction1 between Indoles and Alkylidene Malonates Catalyzed by Pseudo-C3-Symmetric Trisoxazoline Copper(II) Complexes