Lewis Acid Catalysed Asymmetric One-Carbon Ring-Expansion of Prochiral Cyclobutanones

Abstract

Enantioselective methylene insertion into prochiral cyclobutanones is described providing access to chiral β-substituted cyclopentanones as important structural motif in synthesis and natural products. Commercially available trimethylsilyl as well as other silyl diazomethanes act as one-carbon synthon and scandium triflate is found to be a potent Lewis acid catalyst. By using bis(oxazoline) ligands, enantioinduction is achieved for a number of β-substituted cyclopentanones including examples bearing all-carbon quaternary stereocentres.

Recent Developments in Enantioselective Scandium-Catalyzed Transformations

“…Cyclopentanones represent important structural motifs in a wide number of natural products, such as prostaglandins and steroids, making their synthesis challenging. In 2023, Wahl and Tenberge described a novel access to chiral β-substituted cyclopentanones based on an enantioselective scandium-catalyzed methylene insertion into the corresponding prochiral cyclobutanones (Scheme 46) [89]. This desymmetrization was catalyzed in toluene by a chiral catalyst in situ, formed from the between 15 mol% of Sc(OTf) 3 and 10 mol% of chiral bisoxazoline ligand 183 bearing an CEt 2 moiety.…”