Configurational Assignment of Epoxides Using HMBC: DFT-Based Development, Experimental Validation, Scope, and Limitations

The configurational assignment of some epoxides is challenging because of their quasi-planar structure. On the basis of density functional theory calculations of nJCH, we developed a protocol for predicting the configurations of epoxides by correlating the conformation of the epoxide oxygen and its vicinal hydrogens with the HMBC signal intensities observed for the two epoxide carbons. When the dihedral angle between the model epoxide oxygens and their vicinal hydrogen was used as the x-axis, the 2JCH and 3JCH values formed nearly symmetric curves. This finding allowed us to determine the epoxide configuration by analyzing the HMBC signals between the proton adjacent to the epoxide and the two epoxide carbons on the basis of the associated conformation relative to the epoxide oxygen, which was divided into conformational sectors, such as synperiplanar (SP), synclinal (SC), anticlinal (AC), and antiperiplanar (AP). However, slight angular adjustments at the borders between the SP and SC conformations were required, along with the introduction of auxiliary conformations to handle the boundary regions. The reliability and generality of this approach were evaluated using 15 epoxides. Except for an epoxide bearing an acetal oxygen, the present rule correctly assigned the configurations of ring epoxides, consistent with conventional analyses.