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.