Organocatalytic Preparation of Substituted Cyclopentanes: A Mechanistic Study

The reaction mechanism of a tandem conjugate addition/α-alkylation of enals leading to functionalized cyclopentanes catalyzed by O-trimethylsilyldiphenylprolinol was investigated by mass spectrometry, NMR spectroscopy, and DFT calculations. We have shown that the high stereoselectivity of the reaction depends on the energy discrimination between the two stereoisomers formed by the condensation of the α,β-unsaturated aldehyde (cinnamaldehyde) and the catalyst. The stereoselectivity of this step depends on the solvent used. The experimental activation barriers were determined to be E a = 25 ± 7 kJ mol–1 (Arrhenius equation), ΔH ⧧ = 23 ± 7 kJ mol–1, and ΔG ⧧ = 101 ± 9 kJ mol–1 (Eyring equation).