Brønsted Acid-Promoted Cyclodimerization of α,ß-Unsaturated γ-Ketoesters: Construction of Fused Pyrano-ketal-lactones and γ-Ylidene-butenolides.

ABSTRACT

Unprecedented MsOH-promoted diastereoselective cascade dimerization and intramolecular lactonization of readily accessible α,ß-unsaturated γ-ketoesters are presented. The results obtained in this work, control experiments, and density functional theory (DFT) calculations suggested that the initial enolization and E to Z isomerization/equilibration of olefin (C=C) of substrate α,ß-unsaturated γ-ketoesters give a Z-isomer preferentially over an E-isomer. Subsequently, the Z-isomer undergoes intermolecular annulation with α,ß-unsaturated γ-ketoesters via domino Michael addition/ketalization/lactonization steps to furnish fused tetracyclic pyrano-ketal-lactone. However, the Z-isomer prefers intramolecular trans-esterification in a competing pathway and gives bicyclic γ-ylidene-butenolide. The key features of this work include simple Brønsted acid catalysis, the formation of three bonds, two rings, and three contiguous stereogenic centers in a single step, DFT calculations, and the assignment of relative stereochemistry through X-ray diffraction (XRD) and two-dimensional (2D) nuclear magnetic resonance (NMR) analyses.