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.