Copper catalyzed reactions biphasic systems

The Sonogashira coupling reaction of terminal alkynes with aryl or vinyl halides is a useful tool for carbon—carbon bond formation, and has found wide employment in areas such as natural product synthesis, the pharmaceutical industry, and material sciences. Novel recyclable Pd catalysts with fluorous ponytails in the ligand 2,2 -bipyridine were reported in a copper-free Pd-catalyzed Sonogashira reaction in a fluorous biphasic system (FBS) (Equation 4.19). The catalysts are only soluble in perfluorinated solvents at room temperature [41],... 

It is evident from the examples provided in Scheme 5, and many others in the hterature, that copper catalyzed ATRC reactions can be utilized in the synthesis of various substrates that can be used as building blocks for the constraction of complex molecules and natural products. However, as mentioned earlier, the principal drawback of this useful synthetic method until recently remained the large amount of catalyst required to achieve high selectivity towards the desired target product. Various methodologies have been developed to overcome this problem and they include (a) the design of solid supported catalysts, (b) the use of biphasic systems containing fluorous solvents,... 

Covey and Leussing have subsequently carried out detailed studies of the zinc(IT)-catalyzed decarboxylation of oxaloacetate. Two processes are observed using stopped flow techniques an initial absorbance increase being complete in about 30 s and a subsequent absorbance decrease being complete after 15 to 30 min. T e first process is due to metal ion-promoted keto-enol tautomerism and the second to catalyzed decarboxylation. The subsequent protonation of the zinc pyruvate intermediate is rapid and unobservable. The rate constant for the decarboxylation ofZn(oxac)(.etois 7.42 x 10 s at 25 °Cand I = 0.1 M compared with the rate constant 31 x 10 s previously reported at 37 °C (Table 24). Detailed studies of the copper(II)-promoted decarboxylation have also been published. The reaction scheme in this case is summarized in Scheme 27. The release of CO is biphasic as is also the rate of H uptake in the step where pyruvate is formed. Only about 20% of the oxac in the system undergoes decarboxylation within the first 30 s. The remaining 80% is present as Cu(oxac)e ci which does not decarboxylate. The slow rate of CO2 evolution arises from the decarboxylation of a residual level of Cu(oxac)keio which is replenished by reketonization of Cu(oxac)e o,. For the decarboxylation Cu oxac)keto — CO2+ Cu(pyruvate)enoiate) = 0.17 s at 25 °C and / = 0.1 M so that the copper(II) complex decarboxy-lates some 23 times faster than the zinc complex. 

Polyfluorinated BOX ligand 228 provides a useful copper complex catalyst, which can be recovered easily from the reaction mixture by a fluorous solvent system [159]. Benaglia and coworkers reported that an F-BOX ligand with CuOTf catalyzed the asymmetric cyclopropanation of diazoacetate in a CgFig/CHaCN biphasic mixture the F-BOX ligand was readily separated from products by phase separation and recovered from the reaction mixture (Scheme 1.105). 

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