Reactive zinc Reformatsky-type reactions

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... 

In addition to serving as a useful replacement for lithium or magnesium in Barbier-type coupling reactions, SmI also provides advantages over zinc as a reductant in Reformatsky-type coupling reactions (equation 54).The latter only performs well when an activated form of zinc is utilized, and thus the homogeneous conditions afforded by SmI provide the advantage of enhanced reactivity under milder conditions. 

The highly reactive indium powder reported in Sections 6.1 and 6.2 reacts readily with a-haloesters to give an indium Reformatsky-type reagent which will add to ketones and aldehydes to give p-hydroxy esters. The Reformatsky reaction using zinc metal has been used in the preparation of p-hydroxy esters for many years. Recent improvements have made this reaction a very reliable reaction (see Section 3.10). 

Reformatsky reactions have a bad reputation as being difficult to entrain. To the authors experience, however, the reactive donors such as alkyl bromo-acetates do not pose particular problems even under rather conventional conditions. Commercial zinc dust activated by pre-treatment with either iodine of preferentially with cuprous chloride (i.e. Zn(Cu)) readily inserts into these halocarbonyl compound with formation of the corresponding zinc enolates. Protocols 1 and 2 describe prototype examples for Reformatsky reaction in the conventional two-step or Barbier-type set-up, respectively. 

---