Chiral 3‑Acylglutaric Acid Derivatives from Strain-Induced Nucleophilic Retro-Claisen Ring-Opening Reactions

A nucleophilic retro-Claisen ring-opening of donor–acceptor cyclobutenes, formed with high stereocontrol by [3 + 1]-cycloaddition of TIPS-protected enoldiazoacetates with α-acyl sulfur ylides, has been developed. Removal of the TIPS group to form the isolable β-keto ester precedes the strain-induced ring-opening. Various amines, alcohols, thiols, and amino acid derivatives are effective nucleophiles, and their products are formed in very high yields via stoichiometric reactions. The chirality of the reactant donor–acceptor cyclobutenes is fully retained in the ring-opening reactions. The 3-acylglutaric acid products are converted to various valuable structures, including amido-diols, γ-aminobutyric acid (GABA) derivatives, and heterocycles.