Copper catalyzed reactions methodology development

Implied in the stoichiometry of their preparation is the full equivalent of transition metal relative to substrate. Indeed, to this day, cuprates tend to be used in excess in most smaller scale reactions. Over the past decade, however, there has been a noticeable shift toward development of methodology catalytic in Cu(I). The rationale behind the emphasis is in line with the times that is, environmental concerns have come to the fore, placing implied limits on the extent of transition metal usage. Therefore, notwithstanding favorable economic factors associated with copper, it being a base rather than precious metal, much effort has been devoted toward copper-catalyzed reactions, including cross-couplings to arrive at C-N, C-O, and C-H, in addition to C-C bonds. Moreover, tremendous strides have been made in asymmetric versions of perhaps the most fundamental of cuprate reactions 1,4-additions to Michael acceptors. 

Since the first examples of lower and upper rim glycocalixarenes were obtained in 1994 by Marra el al.,106 employing the Mitsunobu reaction or copper(II)-catalyzed glycosylation, the development of efficient synthetic methodologies has allowed the emergence of several examples of ()-, N-, or C-glycosyl calix arenes, and these have recently been reviewed (101-106, Fig. 8).107,10X... 

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,... 

Enantioselective Mannich-type addition of enolate equivalents to imines continues to be an attractive strategy for the preparation of chiral p-amino carbonyl compounds. In the area of copper-catalyzed enantioselective Mannich reactions, a number of outstanding examples have appeared in this decade. In particular, work from Kobayashi s laboratories has led this field in recent years. Kobayashi and coworkers have developed a Cu(OTf) 2/diamine catalyst (121) for highly enantioselective addition of enolate equivalents to N-acylimino esters [36]. This methodology... 

The utilization of copper(I) catalysis in asymmetric transformations is universal due to the special valence electron, Lewis acidity, and coordination characteristic of the metal. Copper salts are easily available, cost-efficient, and nontoxic. Copper(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions are straightforward methodologies for the stereoselective construction of various biologically and medicinally important heterocyclic compounds. In the past 5 years, main endeavors have been paid into catalytic asymmetric [3+2] cycloadditions other types of cycloaddition protocols are relatively less developed. The examples described in this chapter clearly demonstrate the potential of chiral Cu(I) complexes in the synthesis of enantioenriched heterocycles. Further studies may lie in the diversification of catalytic system, reaction type, and catalysis mode. Research in this field is still challenging and highly desirable, and it would be expected that more discoveries will come in the near future. 

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