Reformatsky-Peterson reactions

Reactions of a-sUylalkyl halides with carbonyl compounds using activated zinc have been reported. Reactions of ethyl bromo(trimethylsilyl)acetate with aldehydes and ketones in the presence of zinc/silver-graphite rapidly afford the corresponding a,j8-unsaturated esters (Scheme 2.32) [87]. In this case, the Reformatsky-Peterson reaction sequence proceeds under the mild conditions. 

Scheme 2.32. Synthesis of a,jS-unsaturated esters by the Reformatsky-Peterson reaction.

A stereoselective one-step synthesis of a,j5-unsaturated nitriles through Reformatsky-Peterson reaction has also been reported [88]. A mixture of chloro(trimethylsilyl)acetonitrile, an aliphatic aldehyde, and activated zinc powder is refluxed in THF and quenched with aqueous ammonia to give the corresponding a,yS-unsaturated nitrile with high Z-selectivity (Scheme 2.33). 

Scheme 14.3 Reformatsky reaction/Peterson elimination sequences.15 18...

Reformatsky reaction/Peterson elimination sequence using highly activated Zn(Ag) -graphite preparation of ethyl cyclohexylideneacetate (Structure 14)... 

Reformatsky reactions of a-trimethylsilyl esters have been used to obtain a,(3-unsaturated esters directly from carbonyl substrates in a Peterson-type alkenation,81 as shown in equation (40). 

Carbon-14-labeled TMS acetates are most directly prepared from the corresponding haloacetates, as preparation by the reaction of lithiated acetate esters with trimethylsilyl chloride (TMSCl) would result in a mixture of C- and O-silylated products. The preferred procedme involves reaction of TMSCl with the organozinc reagent of the haloacetate in a modified Reformatsky reaction. An application of this Peterson-olefination sequence is illustrated by the preparation of the antipsoriatic vitamin D derivative 204. Reaction of the anion of benzyl trimethylsilyl[l, 2-"C2]acetate (20ft) with TBS-protected cyclohexa-none-3,5-diol afforded the expected benzyl cyclohexylidene[l,2-"C2]acetate t201i in moderate yield. The subsequent transformation of 201 to the phosphine oxide 202 followed... 

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