Unsymmetric N‑Aryl Substituent Effects on Chiral NHC-Cu: Enantioselectivity and Reactivity Enhancement by Ortho‑H and Syn-Configuration

The
N-aryl substituent effects on chiral C1 NHC’s configuration
and noncovalent interactions were studied by Cu-catalyzed borylation.
An inconspicuous N-aryl ortho-H, which can be found in many chiral
C1 NHC designs, is now explored as a nonclassical hydrogen bonding
site to achieve higher chiral induction ability. According to density
functional theory (DFT) calculations, it cooperates with other noncovalent
interactions, resulting in an unusual dual maxima shape e.r.-Hammett plot. A 2,6-unsymmetric substituted N-aryl on the other
side also allowed for better chiral induction ability (∼3-fold e.r. increase) and higher relative reactivity (increase
to 20:1). A catalyst with a syn-configuration between
the NHC core Ph and the bulkier N-aryl o-substituent,
which is supported by the crystal structures, the DFT calculations,
and nuclear magnetic resonance (NMR), was found to be more effective
than the more regularly hypothesized catalyst with an anti-configuration.
A well-defined chiral NHC-Cu catalyst was then developed for highly
enantioselective B-substituted quaternary center synthesis, which
is effective for both E-/Z-enones
(up to 98% e.e.) and substitution patterns with limited
steric differences at β-positions.