Amides Negishi cross-coupling reaction

Zinc amide 59 shows better chemoselectivity (but lower reactivity) and leads to the formation of aryl- and heteroarylzinc chlorides. Notably, it can be used to achieve [82] directed ortho- and meta-zincation of functionalized aryl nonaflates, thus providing suitable substrates for further Negishi cross-coupling reactions. 

Simple amides and esters 116 were conveniently deprotonated by Zn(tmp)2 (tmp = 2,2,6,6-tetramethylpiperidinyl anion) to generate zinc enolates 117. The zinc enolates 117 were readily coupled with aryl bromides using typical palladium-catalyzed Negishi cross-coupling reactions to give arylketones 118. Enolates formed by this method were suitable for use in aldol reactions that tolerate base-sensitive functional groups. 

Examples of Negishi cross-couplings by this catalyst system are provided in Table 4. The method tolerates cyanides (entries 3 and 4), pyridines (entry 5), amides (entry 7), imides (entry 8), and esters (entry 10). Furthermore, hindered alkenylzincs (geminally or cfs-substituted entries 6-9) are suitable reaction partners. However, the effectiveness of the catalyst is compromised if the electrophile is hindered (e.g., branching in the a or p positions). 

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