Carbon-Heteroatom Bond forming Processes

1 Copper-catalyzed Coupling with Nucleophilic Oxygen and Nitrogen-containing Compounds 

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A plausible mechanism for the Pd-catalyzed Cj/z -P bond forming reactions proposed by Xu et al. is shown below. Oxidative addition of 2-bromothiophene to Pd(0) results in Pd(II) intermediate 83, which then undergoes a reaction with //-butyl phenylphosphite and triethylamine to afford 84. Finally, reductive elimination of 84 furnishes unsymmetrical alkyl arylphosphinate 82, regenerating Pd(0). Although this mechanism seems quite reasonable based on more recent studies of Pd-catalyzed carbon-heteroatom bond-forming processes (see below), alternative mechanisms have also been proposed [81, 82c]. 

Recently, interest in copper-catalyzed carbon-heteroatom bond-forming reactions has shifted to the use of boronic acids as reactive coupling partners [133], One example of carbon-sulfur bond formation is displayed in Scheme 6.65. Lengar and Kappe have reported that, in contrast to the palladium(0)/copper(l)-mediated process described in Scheme 6.55, which leads to carbon-carbon bond formation, reaction of the same starting materials in the presence of 1 equivalent of copper(II) acetate and 2 equivalents of phenanthroline ligand furnishes the corresponding carbon-sulfur cross-coupled product [113]. Whereas the reaction at room temperature needed 4 days to reach completion, microwave irradiation at 85 °C for 45 min in 1,2-dichloroethane provided a 72% isolated yield of the product. 

Stereoselective carbon-carbon and carbon-heteroatom bond forming reactions are among the most fundamental reactions employed for the construction of the molecular frameworks of various biologically active molecules in synthetic organic chemistry. A number of metal-catalyzed asymmetric processes have been developed and have gained wide acceptance, and some are even used on an industrial scale [1],... 

The intra- and intermolecular carbon—heteroatom bond forming reactions using alkenyl epoxides and aziridines have been utilized for the synthesis of heterocyclic compounds.261 There are two major processes for the preparation of heterocycles using these substrates, as illustrated in Scheme 192 (a) intramolecular allylation of alkenyl epoxides and aziridines with Y—H and (b) intermolecular cycloaddition of vinyl epoxides and aziridines with the hetero-cumulenes 627, such as isocyanates, carbodiimides, and isothiocyanates.270... 

Although Ce(IV) derivatives are generally employed as single-electron transfer (SET) oxidants, the authors (Li et al. 2009a) believe that CAN serves as a Lewis acid in the above process in the same way as in other carbon-carbon and carbon-heteroatom bond-forming reactions (Nair et al. 2004a). 

Cross-coupling to form carbon heteroatom bonds occurs by oxidative addition of an organic halide, generation of an aryl- or vinylpalladium amido, alkoxo, tholato, phosphido, silyl, stannyl, germyl, or boryl complex, and reductive elimination (Scheme 2). The relative rates and thermodynamics of the individual steps and the precise structure of the intermediates depend on the substrate and catalyst. A full discussion of the mechanism for each type of substrate and each catalyst is beyond the scope of this review. However, a series of reviews and primary literature has begun to provide information on the overall catalytic process.18,19,22,23,77,186... 

Bartlett PA (1984) Olefin cyclization processes that form carbon-heteroatom bonds. In Hassner A (ed) Asymmetric synthesis, vol 3. Academic, Orlando, FL, p 411... 

Formally copper catalyzed couplings are analogous to palladium and nickel catalyzed reactions. Carbon-carbon and carbon-heteroatom bonds can be formed in such transformations alike. From the mechanistic point of view there is a significant difference between nickel, palladium and copper catalyzed processes however. While in the former cases the catalyst usually oscillates between the 0 and +2 oxidation states, in copper mediated transformations the common oxidation numbers are +1, +2 and +3. 

This review outlines the recent advances in the synthesis of heterocyclic compounds utilizing ruthenium catalysts. The first part is devoted to the synthesis of heterocycles via carbon-heteroatom bond formations. Heterocyclic frameworks are also constructed by ring closure of heteroatom-tethered acyclic molecules. The second part covers the ruthenium-catalyzed carbon-carbon bond forming cyclizations yielding heterocycles. Other examples, in which ruthenium catalysis indirectly participates in heterocycle formation, are collected in the final section. Although a heterocyclic ring was formed without catalysis, ruthenium-catalyzed processes play pivotal roles in such examples. 

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