Esters Negishi cross-coupling reaction

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). 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

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