Copper catalysis, process

The conjugate addition of organometallic reagents R M to an electron-deficient alkene under, for instance, copper catalysis conditions results in a stabilized car-banion that, upon protonation, affords the chiral yS-substituted product (Scheme 7.1, path a). Quenching of the anionic intermediate with an electrophile creates a disubstituted product with two new stereocenters (Scheme 1, path b). With a pro-chiral electrophile, such as an aldehyde, three new stereocenters can be formed in a tandem 1,4-addition-aldol process (Scheme 1, path c). 

The products formed in these reactions are very sensitive to the functionality on the carbenoid. A study of Schechter and coworkers132 using 2-diazo-1,3-indandione (152) nicely illustrates this point. The resulting carbenoid would be expected to be more electrophilic than the one generated from alkyl diazoacetate and consequently ihodium(II) acetate could be used as catalyst. The alkylation products (153) were formed in high yields without any evidence of cycloheptatrienes (Scheme 33). As can be seen in the case for anisole, the reaction was much more selective than the rhodium(II)-catalyzed decomposition of ethyl diazoacetate (Scheme 31), resulting in the exclusive formation of the para product. Application of this alkylation process to the synthesis of a novel p-quinodimethane has been reported.133 Similar alkylation products were formed when dimethyl diazomalonate was decomposed in the presence of aromatic systems, but as these earlier studies134 were carried out either photochemically or by copper catalysis, side reactions also occurred, as can be seen in the reaction with toluene (equation 36). 

Oxazoles of various substitution patterns are well known heterocycles for which a number of methods of synthesis have been reported.129 Acyl carbenes or functionally equivalent species have been found to undergo cyclization with nitriles to give oxazoles in high yield via nitrile ylide intermediates.130,131 This reaction can be induced to occur under thermal, photolytic, or catalytic conditions.129,132,133 Huisgen and coworkers were the first to study this process in some detail.132 Thermolysis (or copper catalysis) of a mixture of ethyl diazoacetate and benzonitrile resulted in the formation of oxazole 254. The isolation of this product is... 

Copper catalysis has also been considered in the past, and has recently received further attention 16]. It appears as a particularly efficient process for the monoaddition of HCN to conjugated olefms (isolated double bonds do not react). 

The mechanism of copper catalysis is obviously related to the halogcnaiing properties of the copper salts the activity is restricted to the halides, CuCN, CuOAc, CufOjSCFa) and CuF being inactive. The addition of halide ions, BrCN or croiyl bromide to CuCN, however, restores an activity comparable to CuBi efficiency. Crotyl bromide is a particularly efficient additive and may be an intermediate in the process. The rate increases by a factor of three in relation to the neat CuBr catalyzed reaction. Yields Itigher than 90% can thus be obtained. Similarly. UBr reactivates the catalyst 16). 

Copper catalysis has been shown to have a dramatic effect on regioselectivity in the protection of sugar derivatives as the acetonide [33]. Compound 47 afforded the acet-onide 48 upon treatment with dimethoxypropane and CUSO4 in acetone. In contrast, the acid-catalyzed acetalization afforded 49 in 90 % yield (Sch. 12). It is suggested that the acid-catalyzed reaction occurs first at the primary alcohol and subsequently migrates to the secondary alcohols to afford 49 whereas the copper-catalyzed process is not reversible. 

Surprisingly, a methylenecyclohexane-derived carbazate akin to (154) gave negligibly more equatorial (55%) than axial attack when treated under the same conditions. > en the rearrangement was initiated with 10 mol % Cu(acac)2, equatorial attack amounted to 65%. The first observation is clearly inconsistent with Evans reaction (154) -> (155). The copper catalysis of the second process suggests the existence of a synthetically unexplored second rearrangement mechanism through a carbenoid. 

This has been accomplished in the double-catalysis process developed by Bayer and Lurgi. Davy Powergas, who is a Lurgi licensee for this process, built the only two plants of this type in the United States which use copper converter gas. They have kept sulfur dioxide emissions well below the guaranteed 500 ppm level. 

The seminal work by the groups of Hartwig and Buchwald in 1994 on aryl amina-tion chemistry has spurred substantial research on C-N bond formation in general and aryl-nitrogen bond formation in particular [114]. Catalytic aryl amine couplings are usually slow processes, especially when copper catalysis is used, often... 

B. Copper Catalysis in Synthetic and Industrial Processes Summary... 

For the large scale production of methylchlorosilanes, especially the dimethyldichlorosilane, which is the source for the production of silicones, e.g. polydimethylsiloxane (PDMS), silicon is reacted with methyl chloride under copper catalysis ( Direct Process , Milller-Rochow Process , see Preface and Scheme 2). 

The potential for sequential copper-catalyzed processes can also be illustrated in the case of formation of fully substituted 1,2,3-triazoles. In this sequence, the same copper catalyst is promoting two distinct types of catalysis [3+2]-cycloaddition and arylation via C-H activation. Each reaction type tolerates both electron-rich and -poor substrates, as well as steric hindrance, adding noteworthy breadth to this scheme. A 4-component sequence using NaNs, rather than an alkyl azide, is shown below. The diamine DMEDA (W.W -dimethylethylenediamine) is used to stabilize the copper catalyst. 

Strict intermolecular diamination of alkenes remains a difficult process in transition-metal catalysis. Still, some interesting reactivity has recently been uncovered for terminal alkenes [122-124]. First, Shi reported the development of diamination of styrenes 18 and 179 under copper catalysis (Scheme 16.49). These protocols make use of three diaziridine derivatives 180-182, which were used as... 

As with the synthesis of indoles, tandem catalytic processes have also received considerable attention. To this end, imidoyl chlorides have proved useful starting materials (Scheme 24.10, disconnection D-3) [71,72]. Scheme 24.14 presents an example from the Zhang group, where imidoyl chloride 31 can be combined with benzyl amine using copper catalysis to deliver the expected benzimidazole in excellent yield [71]. However, it was necessary to include an electron-withdrawing substituent on the imidoyl chloride substrate to ensure good reactivity for example, the trifluoromethyl substituent present in substrate 31. 

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