Reformatsky-type arylations

In 1991, Pattenden exploited the inherent regioselectivity of nucleophilic additions on P-methoxy maleic anhydrides to prepare gomphidic acid (30) by two different routes (Scheme 1.10) [63]. The first one involves an HWE reaction between phosphonate 80 and aryl pyruvate 81 [63b], and the second one is based on a Reformatsky-type reaction of 77 with zinc enolates derived from aryl acetate 79 [63cj. 

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... 

---