A representative number of decalin and hydrindane derivatives 2a-l were prepared in 11-91% yield by means of a cascade reaction of cyclohexanone/cyclopentanone enolates and methyl acrylate through a Michael-Michael ring closure (MIMIRC) process. The relative stereochemistry of the four stereogenic centers formed in all products was determined by analyzing the vicinal coupling constants from the 1H NMR and X-ray crystallography. Such a stereochemical outcome was corroborated by conformational analysis supported by DFT calculations and simulating the 1H NMR spectra of representative products. All products showed the same relative stereochemistry at C-1 and C-8a, while at C-3 and bridgehead carbon C-4a, configurational changes were observed. The present results provide some insights about the scope and limitations of the triple cascade reaction between cycloalkanone enolates with methyl acrylate. This synthetic protocol is still a simple and very practical alternative to generate decalin and hydrindane derivatives with great structural diversity.
Keywords: cycloalkanone enolates; decalin/hydrindane derivatives; double Michael addition; methyl acrylate; stereochemical outcome.