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The Challenge of Linear ( E )‐Enones in the Rh‐Catalyzed, Asymmetric 1,4‐Addition Reaction of Phenylboronic Acid: A DFT Computational Analysis
Author(s) -
Qin HuaLi,
Chen XiaoQing,
Shang ZhenPeng,
Kantchev Eric Assen B.
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201405189
Subject(s) - chemistry , steric effects , ligand (biochemistry) , asymmetric induction , substituent , diene , stereochemistry , substrate (aquarium) , computational chemistry , chiral ligand , catalysis , alkane stereochemistry , density functional theory , enantioselective synthesis , molecule , organic chemistry , biochemistry , natural rubber , receptor , oceanography , geology
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 CC 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.