Selectivity in stepwise (4+3) cycloadditions of furfuryl cations: stereocontrol by highly organized transition states in a nonstop cycloaddition mechanism

D. Hertsen, B. Denoo, O. N. Avci, V. Van Speybroeck, J. Winne, S. Catak
Chemistry - A European Journal


Furfuryl cations are reliable three-carbon dienophiles for a wide range of conjugated dienes and can be generated from simple furan-2-methanol derivatives (furfuryl alcohols) as versatile organic building blocks for the elaboration of complex fused-ring systems. The mechanism of this orbital symmetry-allowed oxyallyl-type (4+3) cycloaddition can be considered either as a concerted or a stepwise carbocationic process. In this work, we have examined the highly selective intermolecular furfuryl cation cycloadditions of (R)-α-phellandrene from a joint experimental and theoretical perspective, in order to gain insight into the factors which govern the stereoselectivity. We have found that these reactions proceed via a stepwise mechanism with a highly pre-organized transition state for the first step, thus reconciling the stepwise mechanism with the experimentally observed high selectivities, and offering a new general explanation as similar pathways were identified with a range of diene reaction partners.