Substituent Effects on the Ring Opening of 2-Aziridinylmethyl Radicals

Substituent effects on the ring-opening reactions of 2-aziridinylmethyl radicals were studied systematically for the first time utilizing the ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p)) method. It was found that various substituents on the nitrogen atom had a relatively small effect on the ring opening of the 2-aziridinylmethyl radical. A π-acceptor substituent at the C₁ position reduced the energy barrier for C−C cleavage dramatically, but it increased the energy barrier for C−N cleavage significantly at the same time. When the C₁ substituent is alkyl, the ring opening should always strongly favor the C−N cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C₁ substituent is CHO (or CO-alkyl, CO-aryl, or CO−OR but not CO−NR₂), the ring opening strongly favors the C−C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C₁ substituent is aryl (or alkenyl or alkynyl), the ring opening should favor the C−C cleavage pathway if the N substituent is alkyl or COR. If both the C₁ substituent and the N substituent are aryl, the ring opening should proceed via both the C−C and C−N cleavage pathways. The solvent effect on the regioselectivity of the ring opening of the 2-aziridinylmethyl radicals was found to be very small. The substituent effects on C−C cleavage could be explained successfully by the spin-delocalization mechanism. For the substituent effects on C−N cleavage, an extraordinary through-bond π-acceptor effect must be taken into account. Furthermore, studies on bicyclic 2-aziridinylmethyl radicals showed that the ring strain could also affect the regiochemistry of the ring-opening reactions.