Photocycloaddition reaction of atropisomeric maleimides: mechanism and selectivity

We report a density functional study on the mechanism of the [2+2] photocyclization of atropisomeric maleimides. Experimentally, the reaction is known to proceed through the triplet state. We have located all relevant S-0 and T-1 minima and transition states, as well as the T-1/S-0 crossing points, and mapped eight stepwise photocyclization pathways for four different conformers in the T-1 state that lead to distinct regioisomers. In the preferred four pathways (one for each conformer) the initially formed C-C bond involves the terminal carbon atom of the alkene moiety. This regioselectivity originates from electrostatic preferences (arising from the charge distribution in the polarized C=C double bonds) and from the different thermodynamic stability of the resulting triplet diradical intermediates (caused by electron donation effects that stabilize the radical centers). The formation of the second C-C bond is blocked in the T-1 state by prohibitively high barriers and thus occurs after intersystem crossing to the ground state. Furthermore, we rationalize substitution effects on enantioselectivity and diastereo-selectivity and identify their origin.