Copper-mediated reaction

Nucleophilic Reactions. Useful nucleophilic substitutions of halothiophenes are readily achieved in copper-mediated reactions. Of particular note is the ready conversion of 3-bromoderivatives to the corresponding 3-chloroderivatives with copper(I)chloride in hot /V, /V- dim ethyl form am i de (26). High yields of alkoxythiophenes are obtained from bromo- and iodothiophenes on reaction with sodium alkoxide in the appropriate alcohol, and catalyzed by copper(II) oxide, a trace of potassium iodide, and in more recent years a phase-transfer catalyst (27). 

As described above, many copper-mediated reactions play important roles in tlie syntlieses of natural and unnatural products. To date natural product syntlieses using organocoppet reagents have beeti accomplisbed, and w ill undoubtedly be increasing greatly from now on. 

The Roles of Cluster Structure in Copper-mediated Reactions... 

Direct aromatic substitution of unactivated aryl halides is slow and generally requires a catalyst to become a useful synthetic method. Copper reagents have been used in some cases in classical procedures for the formation of products from aromatic substitution. In many cases these copper-mediated reactions occur at high temperatures and are substrate dependent. Since the 1970s, transition metal catalysts have been developed for aromatic substitution. Most of the early effort toward developing metal-catalyzed aromatic substitution focused on the formation of... 

The copper)I) arenethiolate complexes 19 [30], first developed and studied by van Koteris group, can be used as catalysts for a number of copper-mediated reactions such as 1,4-addition reactions to enones [31] and 1,6-addition reactions to enynes [32]. 

Use of this technique results in an equivalent of lithium halide being present in the reaction mixture, unlike when the isolated copper arenethiolates are employed. Lithium salts can have very profound effects on copper-mediated reactions, but in this case a similar ee (40%) and complete y selectivity were still obtained for the reaction between 21 and n-BuMgl when the catalyst was prepared from Cut. Nei-... 

Y. Nakamura, M. Okada, A. Sato, H. Horikawa, M. Koura, A. Saito, T. Taguchi, Stereoselective synthesis of (Z)-fluoroalkenes directed to peptide isosteres Copper mediated reaction of trialkylaluminum with 4,4-difluoro-5-hydroxyallylic alcohol derivatives, Tetrahedron 61 (2005) 5741-5753. 

Figure 8-6. Examples of copper-mediated reactions of haloaromatics. In each case, the halogen is replaced by a nucleophile. The mechanisms probably involve intermediates related to 8.3.

Two examples of typical copper-mediated reactions are presented in Fig. 8-6, and illustrate the replacement of halide by hydroxide or cyanide. Yields in these reactions are frequently excellent, even if the precise mechanistic details are often somewhat unclear ... 

These copper-mediated reactions very often involve dinuclear intermediates, but detailed mechanistic studies on stoichiometric systems are relatively few. The key features are the formation of p-peroxo or p-superoxo complexes by electron transfer from cop-per(i) to dioxygen. The co-ordinated oxygen may then act as an electrophile to the aromatic ring. A possible mechanism for the ortho-hydroxylation of phenol by dioxygen in the presence of copper catalysts is shown in Fig. 9-29. 

Copper-mediated reaction of a 1,1-zinc, boron alkenyl bimetallic with an electrophile preparation of 1-chloro-5-oxo-6-undecyne23... 

A few reports involving copper-mediated substitution of selenophenes with heteroatoms (N, S) have appeared. The preparation of 2-amidoselenophenes (e.g., 48) was accomplished by treating 45 with amides in the presence of copper(l) iodide and ethylenediamine <2006JOC1552>. A similar copper-mediated reaction involving thiols was utilized to prepare sulfur-substituted selenophenes (e.g., 49) <2005TL2647>. 

Most recently. Brown et al. and Yamamoto et at. have independently explored organic boron-copper mediated reactions. For example, dialkenylchloroboranes (3, readily available through the reaction of alkynes with chloroborane-ethyl... 

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