title: Automatic Reaction Pathway Search via Combined Molecular Dynamics and Coordinate Driving Method.
abstract: We proposed and implemented a combined molecular dynamics and coordinate driving (MD/CD) method for automatically searching multistep reaction pathways of chemical reactions. In this approach, the molecular dynamic (MD) method at the molecular mechanics (MM) or semiempirical quantum mechanical (QM) level is employed to explore the conformational space of the minimum structures, and the modified coordinate driving (CD) method is used to build reaction pathways for representative conformers. The MD/CD method is first applied to two model reactions (the Claisen rearrangement and the intermolecular aldol reaction). By comparing the obtained results with those of the existing methods, we found that the MD/CD method has a comparable performance in searching low-energy reaction pathways. Then, the MD/CD method is further applied to investigate two reactions: the electrocyclic reaction of benzocyclobutene-7-carboxaldehyde and the intramolecular Diels-Alder reaction of ketothioester with 11 effectively rotatable single bonds. For the first reaction, our results can correctly account for its torquoselectivity. For the second one, our method predicts eight reaction channels, leading to eight different stereo- and regioselective products. The MD/CD method is expected to become an efficient and cost-effective theoretical tool for automatically searching low-energy reaction pathways for relatively complex chemical reactions.
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Manyi
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Zou
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Mesoscopic Chemistry of Ministry of Education, Institute of Theoretical and Computational Chemistry, Nanjing University , Nanjing 210023, People's Republic of China.
authors.forename: Shuhua
authors.identifier: http://orcid.org/0000-0001-6756-057X
authors.initials: S
authors.lastname: Li