Advances on Quasi-classical Molecular Dynamics of Organic Reaction Mechanisms

doi:10.6023/cjoc202102036

Abstract

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

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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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Fig. & Tab. 21

Figure 1. A bifurcating potential energy surface

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

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

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

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

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

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

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

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

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

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

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

Scheme 2. Two pathways of Prins rearrangement

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

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

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

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]

Table 2. Number of the trajectories

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

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)

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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