Practical and robust method for stereoselective preparations of ketene silyl (thio)acetal derivatives and NaOH-catalyzed crossed-Claisen condensation between ketene silyl acetals and methyl esters

We developed an efficient, practical, and robust method for stereoselective preparations of (Z)-ketene trimethylsilyl (TMS) thioacetals from thioesters and alkyl (1Z)- or (1Z,3E)-1,3-bis(TMS)dienol ethers from alkyl β-ketoesters. The former preparation was performed by convenient procedure (LDA-TMSCl, 0-5 °C, 2.5 h), while the latter preparation involved convenient method A (2NaHMDS-2TMSCl) and cost-effective method B (NaH, NaHMDS-2TMSCl). The first catalytic NaOH-catalyzed crossed-Claisen condensation between ketene silyl acetals and methyl esters proceeded successfully to give a variety of α-monomethyl β-ketoesters and inaccessible α,α-disubstituted β-ketoesters. For further extension, a couple of Claisen-aldol tandem reactions of the obtained β-ketoester analogues utilizing TiCl4 and TiCl4-Bu3N reagents smoothly proceeded with good to excellent stereoselectivity.

Graphical abstractDownload full-size image