Department of Chemistry and the Research Center for Smart Molecules, Rikkyo University, Nishi-Ikebukuro, Toshima-ku, Tokyo 171-8501, Japan.
J Org Chem. 2011 Oct 21;76(20):8294-9. doi: 10.1021/jo201485y. Epub 2011 Sep 7.
The reaction of an α-haloketone with a nucleophile has three reaction channels: carbonyl addition, direct substitution, and proton abstraction. DFT calculations for the reaction of PhCOCH(2)Br with OH(-) showed that there exists an addition/substitution TS on the potential energy surface, in which OH(-) interacts with both the α- and carbonyl carbons. The intrinsic reaction coordinate calculations revealed that the TS serves as the TS for direct substitution for XC(6)H(4)COCH(2)Br with an electron-donating X or a X less electron-withdrawing than m-Cl, whereas the TS serves as the TS for carbonyl addition for derivatives with a X more electron-withdrawing than m-CF(3). Trajectory calculations starting at respective TS indicated that the single TS can serve for the two mechanisms, substitution and addition, through path bifurcation after the TS for borderline substrates. The reaction is the first example of dynamic path bifurcation for fundamental reaction types of carbonyl addition and substitution.
α-卤代酮与亲核试剂的反应有三个反应通道：羰基加成、直接取代和质子抽提。DFT 计算表明，PhCOCH(2)Br 与 OH(-)的反应存在一个加成/取代过渡态（TS），其中 OH(-)与α-位和羰基碳都相互作用。内禀反应坐标计算表明，对于 XC(6)H(4)COCH(2)Br 与给电子 X 或比 m-Cl 吸电子能力弱的 X 的直接取代，TS 是 TS；而对于比 m-CF(3)吸电子能力强的衍生物，TS 是羰基加成的 TS。从各自的 TS 开始的轨迹计算表明，对于边界底物，TS 后通过路径分叉，单个 TS 可以用于两种机制，取代和加成。该反应是羰基加成和取代基本反应类型的动态路径分叉的第一个例子。
