What question did this study set out to answer?

The aim is to create a reliable method for synthesizing cyclic C-2 silyl enol ethers from tetrahydrofuran-3-ones.

March 29, 2026Organic Letters1 citations

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

CBCharlotte BoullierCentre National de la Recherche Scientifique SGSigrid GavelleCentre National de la Recherche Scientifique JLJérôme LhosteCentre National de la Recherche Scientifique

Key Points

The aim is to create a reliable method for synthesizing cyclic C-2 silyl enol ethers from tetrahydrofuran-3-ones.
Utilized TIPS-diazoacetone and TIPS-diazoketones as starting materials.
Employed LDA-induced aldol addition for initial synthesis.
Conducted a novel 1,3-(C→O) silyl shift and intramolecular O-H insertion tandem process.
Performed reactions using [Rh(nbd)Cl]2 as a catalyst in refluxing THF.
Successfully generated a variety of regiodefined stable silyl enol ethers (25 examples).
Achieved high cis selectivity in the synthesis (2 examples).
Demonstrated an effective two-step synthesis approach.

Abstract

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 cis 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)Cl2 (2 mol %) in refluxing THF.

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