title: The challenge of linear (E)-enones in the Rh-catalyzed, asymmetric 1,4-addition reaction of phenylboronic acid: a DFT computational analysis.
abstract: Why are linear (E)-enones such challenging substrates in the Rh-catalyzed asymmetric arylation with boronic acids, which is one of the most important asymmetric catalysis methods? DFT computations show that these substrates adopt a specific conformation in which the largest substituent is antiperiplanar to Rh(I) π-complexed with the C = C bond within the enantioselectivity-determining carborhodation transition state. Additionally, for such structures, there is a strong, but not exclusive, preference for s-cis enone conformation. This folding minimizes steric interactions between the substrate and the ligand, and hence reduces the enantioselectivity. This idea is further confirmed by investigating three computation-only substrate "probes", one of which is capable of double asymmetric induction, and a recent computationally designed 1,5-diene ligand. On average, excellent agreement between predicted and experimental enantioselectivity was attained by a three-pronged approach: 1) thorough conformational search within ligand and substrate subunits to locate the most preferred carborhodation transition state; 2) including dispersion interaction and long-range corrections by SMD/ωB97xD/DGDZVP level of theory; and 3) full substrate and ligand modeling. Based on the results, a theory-enhanced enantioselectivity model that is applicable to both chiral diene and diphosphane ligands is proposed.
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070 (P. R. China). qinhuali@whut.edu.cn, hqhuali@gmail.com.
authors.forename: Hua-Li
authors.initials: HL
authors.lastname: Qin
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Chen
authors.forename: Zhen-Peng
authors.initials: ZP
authors.lastname: Shang
authors.forename: Eric Assen B
authors.initials: EA
authors.lastname: Kantchev
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D002384:Catalysis; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001897:Boronic Acids; D012238:Rhodium; C010686:benzeneboronic acid
keywords: chirality; density functional calculations; diene ligands; phosphane ligands; rhodium