Cross-coupling methodology, copper-catalyzed

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

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. 

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