The Challenge of Linear (E)-Enones in the Rh-Catalyzed, Asymmetric 1,4-Addition Reaction of Phenylboronic Acid: A DFT Computational Analysis

摘要

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 pi-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/omega B97xD/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.

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