Access to Regiodefined Tetrahydrofuran-3-one-Derived C-2 Silyl Enol Ethers from α-Triisopropylsilyl-α-diazoketones: The TIPS Trick

The generation of cyclic C-2 silyl enol ethers from the corresponding tetrahydrofuran-3-ones remains a challenge to date. This work provides an alternative two-step approach to access a wide range of regiodefined stable tetrahydrofuran-3-one-derived α-triisopropylsilyl (TIPS) enol ethers from TIPS-diazoacetone (25 examples described) and by extension from TIPS-diazoketones with a high <i>cis</i> selectivity (2 examples). The method involves LDA-induced aldol addition, followed by an unprecedented 1,3-(C→O) silyl shift/intramolecular O-H insertion tandem process, catalyzed by [Rh(nbd)Cl]₂ (2 mol %) in refluxing THF.