Direct carbon-carbon bond formation via chemoselective soft enolization of thioesters: a remarkably simple and versatile crossed-Claisen reaction applied to the synthesis of LY294002.

Thioesters undergo chemoselective soft enolization and acylation by N-acylbenzotriazoles on treatment with MgBr2·OEt2 and i-Pr2NEt to give β-keto thioesters. Prior enolate formation is not required, and the reaction is conducted using untreated CH2Cl2 open to the air. The coupled products are stable synthetic equivalents of β-keto acids and can be converted directly into β-keto esters, β-keto amides, and β-diketones under mild conditions. The utility of this carbon−carbon bond-forming method is shown through the synthesis of the PI3-K inhibitor LY294002.