The Fürst-Plattner rule allows us to predict the regio- and stereochemical outcome of epoxide-opening reactions when the epoxide is present on a six-membered ring. The rule states that 1,2-trans-diaxial products are formed preferntially, which often then undergo ring-flip to the more stable equatorially-substituted chair conformers.
If we consider the epoxide opening shown below (with an acetic acid nucleophile), the SN2 nature of the substitution reaction ensures an anti-relationship between the hydroxyl and acetate substituent.[1,2] But it is the regioselectivity that is the important consideration here, as the site of nucleophilic attack dictates which regioisomer is created and also the stereochemistry of the anti-arranged oxy-substituents at the 4- and 5-positions relative to the phenyl substituent at the 2-position.
The Fürst-Plattner Rule Predicts the Formation of 1,2-Trans-Diaxial Products
The observed 1,2-trans-diaxial outcome is consistent with the Fürst-Plattner rule.[1] The observed preference for attack at the 5-position can be explained by invoking the half-chair conformation shown below, where the phenyl group occupies a pseudo-equatorial position.
Attack at C-5 is along a pseudo-axial trajectory, which allows the reaction to proceed through a chair-like transition state and leads to the observed product (via an anti-periplanar alignment).[2] Attack at C-4, which would lead to the all-equatorially substituted product, is disfavoured because the reaction would have to proceed through a boat-like transition state. As a result, the all-equatorial product is not observed.
One should note that in these types of reactions, the initially formed 1,2-trans-diaxial products will often ring-flip to the more thermodynamically stable conformers.
References
1) A. Fürst, P. A. Plattner, Helv. Chem. Acta, 1949, 32, 275.
2) B. Schmidt, J. Chem. Soc., Perkin Trans. 1, 1999, 2627.
Comments