Copper catalyzed reactions active ligand development

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

A parallel development was initiated by the first publications from Sawamoto and Matyjaszweski. They reported independently on the transition-metal-catalyzed polymerization of various vinyl monomers (14,15). The technique, which was termed atom transfer radical polymerization (ATRP), uses an activated alkyl halide as initiator, and a transition-metal complex in its lower oxidation state as the catalyst. Similar to the nitroxide-mediated polymerization, ATRP is based on the reversible termination of growing radicals. ATRP was developed as an extension of atom transfer radical addition (ATRA), the so-called Kharasch reaction (16). ATRP turned out to be a versatile technique for the controlled polymerization of styrene derivatives, acrylates, methacrylates, etc. Because of the use of activated alkyl halides as initiators, the introduction of functional endgroups in the polymer chain turned out to be easy (17-22). Although many different transition metals have been used in ATRP, by far the most frequently used metal is copper. Nitrogen-based ligands, eg substituted bipyridines (14), alkyl pyridinimine (Schiff s base) (23), and multidentate tertiary alkyl amines (24), are used to solubilize the metal salt and to adjust its redox potential in order to match the requirements for an ATRP catalyst. In conjunction with copper, the most powerful ligand at present is probably tris[2-(dimethylamino)ethyl)]amine (Mee-TREN) (25). 

Evans and coworkers have developed an enantioselective copper-catalyzed ni-troaldol reaction that does not require the use of amine base. A catalyst derived from ligand (158) and Cu(OAc)2 was developed to act as a weakly Lewis acidic metal center capable of electrophile activation. The acetate counterion was chosen owing to its moderate basicity in the hope of facilitating nitroalkane deprotonation. This catalyst system performs admirably in additions of (154) to a broad scope of aldehydes (157) leading to nitroaldol products (159) in good yields with excellent enantioselectivity (Scheme 17.32). 

The author expected that a reaction with a chiral ligand which coordinates to a copper atom could produce optically active 2-(aminomethyl)indoles. Knochel recently developed a novel asymmetric synthesis of chiral propargylamines with excellent ee values through a copper-catalyzed asymmetric Mannich-type reaction of alkynes with an aldehyde and a secondary amine using QUINAP as a chiral ligand (up to 98% ee) [1-3]. Carreira reported the similar synthesis of propargylic amine in up to 99% ee with PINAP [4, 5]. The author initially examined the... 

During the past few decades, transition metal-catalyzed cross-coupling reactions have become a powerful tool for the construction of C—C and C-heteroatom bonds [1]. This strategy allows the conceptually simple and yet powerful and reliable approach for synthesizing structurally complex pharmaceuticals and biologically active molecules. The two most vastly used transition metal catalysts in carbon-heteroatom bond formation are palladium (mainly depends on its ancillary ligands) and copper (depends on the optimization of the catalytic system as a whole copper source, solvent, base, concentrations, etc.). Besides, considerable developments have also been made with other transition metal catalysts such as nickel, iron, etc. 

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