The Stereochemical Outcome of Electrophilic Addition Reactions on the 5,6-Double Bond in the Spinosyns

The electrophilic addition of reagents to the 5,6-double bond in spinosyn A and spinosyn D systems occurred with high π-diastereofacial selectivity. Addition occurred preferentially from the β face of the molecule with selectivities ranging from 5:1 to better than 30:1. Various NMR properties were investigated in order to distinguish the β and α isomers with the help of theoretical models of the products. These NMR properties include a 13C γ effect to C-11 and vicinal coupling between H-4 and H-5. To help rationalize the selectivity, computational studies on the transition states for epoxidation were calculated using density functional theory. The results indicate that β epoxidation is favored and that the geometries of the transition structures are consistent with torsional steering being the source of the selectivity.