Two-carbon homologation of ketones via sily ketene acetals: Synthesis of α,β-unsaturated acids and α-trimethylsilyl δ-ketoacids

The reaction of C,O,O-tris(trimethylsilyl)ketene acetal 1 with saturated, cyclic and aromatic ketones 2 proceeds smoothly in the presence of titanium chloride to give (E)-α,β-unsaturated carboxylic acids 3 with fairly good stereoselectivity. With α,β-unsaturated ketones 4, α-trimethylsilyl δ-ketoacids 5 (syn + anti) are obtained according to Michael-type 1,4 addition. These diastereoisomers are separated and the configurations of 5a are achieved by X-ray molecular analysis.

The trisilylated reagent 1 reacts with saturated ketones to give α,β-unsaturated acids and with α,β-unsaturated ketones to give α-trimethylsilyl δ-ketoacids.Figure optionsDownload as PowerPoint slide