Wang Yi-Min, Fu Yao, Liu Lei, Guo Qing-Xiang
Department of Chemistry, University of Science and Technology of China, Hefei 230026, China.
J Org Chem. 2005 Apr 29;70(9):3633-40. doi: 10.1021/jo048068a.
[reaction: see text] 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 pi-acceptor substituent at the C(1) 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 C(1) 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 C(1) substituent is CHO (or CO-alkyl, CO-aryl, or CO-OR but not CO-NR(2)), the ring opening strongly favors the C-C cleavage pathway, regardless of whether the N substituent is alkyl, aryl, or COR. When the C(1) 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 C(1) 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 pi-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.
[反应：见正文] 首次使用ONIOM(QCISD(T)/6-311+G(2d,2p):B3LYP/6-311+G(3df,2p))方法系统地研究了取代基对2-氮丙啶基甲基自由基开环反应的影响。研究发现，氮原子上的各种取代基对2-氮丙啶基甲基自由基的开环影响相对较小。C(1)位的π-受体取代基显著降低了C-C键断裂的能垒，但同时也显著增加了C-N键断裂的能垒。当C(1)位取代基为烷基时，无论N位取代基是烷基、芳基还是COR，开环总是强烈倾向于C-N键断裂途径。当C(1)位取代基为CHO（或CO-烷基、CO-芳基或CO-OR，但不是CO-NR₂）时，无论N位取代基是烷基、芳基还是COR，开环都强烈倾向于C-C键断裂途径。当C(1)位取代基为芳基（或烯基或炔基）时，如果N位取代基是烷基或COR，开环应倾向于C-C键断裂途径。如果C(1)位取代基和N位取代基都是芳基，开环应通过C-C键和C-N键断裂途径进行。发现溶剂对2-氮丙啶基甲基自由基开环区域选择性的影响非常小。取代基对C-C键断裂的影响可以通过自旋离域机制成功解释。对于取代基对C-N键断裂的影响，必须考虑一种特殊的通过键的π-受体效应。此外，对双环2-氮丙啶基甲基自由基的研究表明，环张力也会影响开环反应的区域化学。
