Enantioselective Route to beta-Silyl-delta-keto Esters by Organocatalyzed Regioselective Michael Addition of Methyl Ketones to a (Silylmethylene)malonate and Their Use in Natural Product Synthesis

[摘要]：The direct Michael addition of alkyl methyl ketones through the acetyl methyl terminal to diethyl {[dimethyl(phenyl) silyl] methylene} malonate was catalyzed by the (S)-N-(pyrrolidin-2-ylmethyl)pyrrolidine/trifluoroacetic acid combination with high yield and excellent regio- and enantioselectivity. The ketone adducts can easily undergo de-ethoxycarbonylation to give beta-silyl-delta-keto esters with excellent synthetic potential. This has been demonstrated by the synthesis of a suitably substituted beta-silyl-delta-keto ester as an advanced intermediate for a chiral hydroxylated pyrrolidine natural product, (+)-preussin. Silicon-controlled diastereoselective reduction of the ketone functionality of beta-silyl-delta-keto esters followed by lactonization of the resulting hydroxy esters gave disubstituted delta-valerolactones. Advanced intermediates for the antipodes of natural products, namely (+)-massoialactone and (+)-mevinolin analogue, and natural products, namely (-)-tetrahydrolipstatin and (+)-5-hexadecanolide, have been achieved.

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