有机反应机制的准经典分子动态学研究进展

doi:10.6023/cjoc202102036

摘要/Abstract

准经典分子动态学模拟方法结合了经典分子动力学和电子结构理论, 从原子/分子层面研究化学反应的动态机制, 不但能模拟反应体系中相应产物或中间体的统计学分布, 还可提供时间尺度下化学键生成/断裂的信息. 密度泛函理论(DFT)计算在反应机制研究中已被广泛应用, 但从准经典分子动态学角度的研究还相对较少, 比如分叉过渡态的现象及其选择性、环加成协同机制中出现的分步过程以及绕过常见的中间体而直接生成产物等. 这些新颖机制的研究通常需要分子动态学, 有些甚至打破了传统过渡态理论的认知. 综述了近年来有机化学反应机制的准经典分子动态学研究进展, 强调机制中的动态学效应, 旨在加深人们对有机反应机制的理解并拓宽有机化学理论.

关键词: 准经典分子动态学, 分叉过渡态, 协同机制, 分步机制, 动态学效应

Quasi-classical molecular dynamics is a computational method that combines classical molecular dynamics and electronic structure theory, which can not only simulate the statistics of the corresponding products or intermediates in the reaction mechanism, but also provide dynamic information of chemical bond formation/cleavage on time scales. Density functional theory (DFT) calculation has been widely used in the research of reaction mechanism, but there are relatively few studies from the perspective of quasi-classical molecular dynamics, such as the phenomenon of bifurcations of transition states and their selectivity, stepwise processes appear in the concerted mechanism of cycloaddition, bypassing common intermediates and directly generating products, etc. These novel mechanism processes often require molecular dynamics, and some even break the cognition of traditional transition state theory. The recent research progress of quasi-classical molecular dynamics of organic chemical reaction mechanisms is reviewed, with emphasis on the dynamic effect in the mechanism, in order to deepening people's understanding of organic reaction mechanisms and broaden the theory of organic chemistry.

Key words: quasi-classical molecular dynamic, bifurcation of transition state, concerted mechanism, stepwise mechanism, dynamic effect

引用此文

张凯瑞, 王亚亚, 朱宏丹, 彭谦. 有机反应机制的准经典分子动态学研究进展[J]. 有机化学, 2021, 41(10): 3995-4006.

Kairui Zhang, Yaya Wang, Hongdan Zhu, Qian Peng. Advances on Quasi-classical Molecular Dynamics of Organic Reaction Mechanisms[J]. Chinese Journal of Organic Chemistry, 2021, 41(10): 3995-4006.

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图/表 21

图1. 分叉过渡态势能面

Figure 1. A bifurcating potential energy surface

图2. 环戊二烯二聚反应势能面

Figure 2. Free energy profiles for the dimerization of cyclopentadiene All calculations were performed using B3LYP/6-31G* level of theory. The bond lengths are in angstroms

图3. 金催化扩环和螺环化反应的势能面

Figure 3. Free energy profiles for gold-catalyzed ring expansion and spirocyclization reactions QM calculations were performed using B3LYP/6-31G*(SDD for Au)//SMD (toluene) level of theory

图4. 1,3-丁二烯和氧化吡啶鎓叶立德环加成反应势能面

Figure 4. Free energy profiles for cycloaddition of butadiene and oxido-pyrylium ylides QM calculations were performed using M06-2X/6-311+G**//SMD (DCM) level of theory. The bond lengths are in angstroms

图5. 4种双周环分叉过渡态和[6+4]环加成反应势能面

Figure 5. Four bipericyclic transition states and free energy profiles for [6+4] cycloadditions QM calculations were performed using PCM(diethyl ether)/M06-2X/ 6-311+G**//B3LYP-D3/6-31G* level of theory. The bond lengths are in angstroms

图6. Spinosyn A生物合成中的[6+4]、[4+2]环加成竞争反应势能面

Figure 6. Free energy profiles for competition of [6+4] and [4+2] cycloaddition in the biosynthesis of spinosyn A QM calculations were performed using SMD(H2O)/M06-2X/def2-TZVPP//B3LYP-D3(BJ)/6-31+G** level of theory. The bond lengths are in angstroms

图7. Heronamide A生物合成中的[6+4]、[4+2]环加成反应势能面

Figure 7. Free energy profiles for [6+4] and [4+2] cycloadditions in biosynthesis of heronamide A QM calculations were performed using M06-2X/6-311+G**//B3LYP /6-31G* level of theory. The bond lengths are in angstroms

图8. 三分叉环加成反应势能面

Figure 8. Free energy profiles for tripericyclic cycloaddition QM calculations were performed using ωB97X-D/6-31G* level of theory. The bond lengths are in angstroms

图9. 1,2,6-庚三烯重排势能面

Figure 9. Free energy profiles for 1,2,6-heptatriene rearrangement QM calculations were performed using CASSCF(8,8)/6-31G* level of theory

图式1. 两种[3,3] σ-重排反应路径

Scheme 1. Two possible [3,3] σ-rearrangement pathways

Structure	ΔG	Structure	ΔG	Structure	ΔG
50	0.0	50_F	0.0	50_Cl	0.0
TS-51	41.0	TS_F-51	45.8	TS_Cl-51	44.8
TS-52	36.9	TS_F-52	43.6	TS_Cl-52	35.8
53	–11.5	53_F	–6.9	53_Cl	–18.9
54	–11.5	54_F	–10.9	54_Cl	–10.7

表1. σ-重排中各中间体、过渡态及其卤代物自由能a

Table 1. Free energies of intermediates, transition states and their halo-genated derivatives in σ-rearrangement

图10. 松香酸合成中碳正离子重排的势能面

Figure 10. Free energy profiles for a carbocation rearrangement in the synthesis of abietic acid QM calculations were performed using B3LYP/6-31+G** level of theory

图式2. Prins重排中的两种反应路径

Scheme 2. Two pathways of Prins rearrangement

图式3. CCl2和CF2与乙烯的反应以及双自由基基团的翻转

Scheme 3. Reactions of CCl2 and CF2 with ethylene and the inversion of diradical complex QM calculations were performed using UB3LYP/6-31G* and mUB3LYP/ 6-31G* (HF exchange in UB3LYP was reduced from 20% to 12%, and the contribution of local exchange was adjusted to 88%) level of theory

图式4. 6类对称和2类不对称D-A反应

Scheme 4. Six types of symmetrical and two types of asymmetric D-A reactions QM calculations were performed using UB3LYP/6-31G* level of theory

图式5. R12, R13的一般D-A反应和R14~R17的DDA反应 (R17'展示了R17的双自由基机制)

Scheme 5. General D-A reactions of R12, R13, and DDA reactions of R14~R17 (R17' shows the diradical mechanism of R17) The electronic energies above and below the arrows are the activation energy and distorsion energy of the reaction under the concerted mecha- nism (the corresponding electronic energy in the stepwise mechanism are given in brackets). QM calculations were performed using (U)M06- 2X/6-311+G** level of theory. Energies are given in kcal/mol

图11. 铁催化ODA反应势能图

Figure 11. Free energy profiles for Fe-catalyzed ODA reaction The corresponding free energies of the five-coordinated Fe-catalyzed structures (such as 65') is indicated in brackets. QM calculations were performed using SMD/B3LYP-D3/6-31G*(def2-TZVP for Fe) level of theory

	Gas	Solution	Solution+OEEF
Uncatalyzed	100 (0^c) [5^d]	100 (0^c) [6^d]	—
6-c ⁴Fe^a	100 (21^c) [40^d]	130 (26^c) [50^d]	130 (86^c) [174^d]
5-c ⁴Fe^b	130 (39^c) [59^d]	130 (54^c) [98^d]	130 (88^c) [235^d]
5-c ⁶Fe^b	100 (74^c) [103^d]	130 (87^c) [199^d]	130 (96^c) [414^d]

表2. 准经典分子动态学轨迹数量

Table 2. Number of the trajectories

图12. (a) 13CH4和(b)苯的C—H活化势能面

Figure 12. Free energy profiles for C—H activation of (a) 13CH4 and (b) benzene QM calculations were performed using M06/6-31G*[LANL2DZ for Ir] level of theory

图13. Cp*M(III) (M=Co, Rh, Ir)催化的1,4-负氢迁移机理More O'Ferrall-Jencks图

Figure 13. A More O'Ferrall-Jencks-type diagram for the 1,4- hydride transfer mechanism mediated by Cp*M(III) (M=Co, Rh, Ir)

图14. Pictet-Spengler反应势能面

Figure 14. Free energy profiles for Pictet-Spengler reaction QM calculations were performed using PBE1PBE/6-311+G** level of theory

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