J. Heyrovský Institute of Physical Chemistry, The Czech Academy of Sciences , Dolejškova 2155/3, 182 23 Prague 8, Czech Republic.
Department of Chemistry, Stanford University , Stanford, California 94305-5080, United States.
J Am Chem Soc. 2017 Feb 15;139(6):2396-2407. doi: 10.1021/jacs.6b11995. Epub 2017 Feb 2.
The ability of an Fe═O intermediate in SyrB2 to perform chlorination versus hydroxylation was computationally evaluated for different substrates that had been studied experimentally. The π-trajectory for H atom abstraction (Fe═O oriented perpendicular to the C-H bond of substrate) was found to lead to the S = 2 five-coordinate HO-Fe-Cl complex with the C of the substrate, π-oriented relative to both the Cl and the OH ligands. From this ferric intermediate, hydroxylation is thermodynamically favored, but chlorination is intrinsically more reactive due to the energy splitting between two key redox-active dπ* frontier molecular orbitals (FMOs). The splitting is determined by the differential ligand field effect of Cl versus OH on the Fe center. This makes chlorination effectively competitive with hydroxylation. Chlorination versus hydroxylation selectivity is then determined by the orientation of the substrate with respect to the HO-Fe-Cl plane that controls either the Cl or the OH to rebound depending on the relative π-overlap with the substrate C radical. The differential contribution of the two FMOs to chlorination versus hydroxylation selectivity in SyrB2 is related to a reaction mechanism that involves two asynchronous transfers: electron transfer from the substrate radical to the iron center followed by late ligand (Cl or OH) transfer to the substrate.
为不同的实验研究过的底物计算了 SyrB2 中 Fe═O 中间体进行氯化与羟化的能力。发现 H 原子离域（Fe═O 垂直于底物的 C-H 键定向）的 π 轨道导致 S = 2 五配位 HO-Fe-Cl 配合物，其中底物的 C 相对于 Cl 和 OH 配体处于π 取向。从这个三价铁中间体来看，羟化是热力学有利的，但氯化由于两个关键氧化还原活性 dπ*前线分子轨道（FMO）之间的能量分裂而具有内在更高的反应性。这种分裂取决于 Cl 与 OH 对 Fe 中心的配体场效应的差异。这使得氯化实际上与羟化具有竞争力。因此，氯化与羟化的选择性取决于底物相对于 HO-Fe-Cl 平面的取向，这控制着 Cl 或 OH 与底物 C 自由基的反弹，具体取决于与底物的相对 π 重叠。SyrB2 中两个 FMO 对氯化与羟化选择性的差异贡献与涉及两个异步转移的反应机制有关：从底物自由基到铁中心的电子转移，然后是迟滞配体（Cl 或 OH）向底物的转移。
