Enantiocontrol by assembled attractive interactions in copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes: OH⋯O/sp³-CH⋯O two-point hydrogen bonding combined with dispersive attractions

Abstract

A chiral copper catalyst selects enantiofaces by assembled attractive interactions.

Copper(I)‐Catalyzed Enantioconvergent Borylation of Racemic Benzyl Chlorides Enabled by Quadrant‐by‐Quadrant Structure Modification of Chiral Bisphosphine Ligands

“…The important factors determining the enantioselectivity were evaluated by structural analysis of the transition states based on noncovalent interactions (NCIPLOT; see Figure S3) . The interaction between the benzylic hydrogen atom and the oxygen atom of the methoxide coordinated to the copper center, which resembles hydrogen bonding, is shown as an “attractive” blue isosurface in both transition states . The boryl group moves toward the sterically less hindered space to avoid steric repulsion with the bulky alkyl substituents of the ligand, thus creating a rigid chiral environment for an enantioselective reaction with the radical species.…”

Copper(I)‐Catalyzed Enantioconvergent Borylation of Racemic Benzyl Chlorides Enabled by Quadrant‐by‐Quadrant Structure Modification of Chiral Bisphosphine Ligands

“…[21] Theinteraction between the benzylic hydrogen atom and the oxygen atom of the methoxide coordinated to the copper center, which resembles hydrogen bonding,i ss hown as an "attractive" blue isosurface in both transition states. [22] The boryl group moves toward the sterically less hindered space to avoid steric repulsion with the bulky alkyl substituents of the ligand, thus creating ar igid chiral environment for an enantioselective reaction with the radical species.F urthermore,astrong CÀH/p interaction between the phenyl ring of the substrate and the methyl groups of the B(pin) was observed, as evident from the large isosurface in the NCIPLOTanalysis of the transition state TS1 for the major enantiomer (S)-3i.C onversely,i nTS2,w hich leads to the minor enantiomer (R)-3i,t he loose contact between the phenyl ring and the pinacol moiety of the B(pin) unit suggests the presence of weak CÀH/p interactions.I na ddition, the steric interaction between the adamantyl moieties of the ligand and the aromatic substituent of the substrate distorts the conformation of the copper(II)-complex, thus destabilizing TS2.T his analysis of the C À H/p interactions is consistent with the experimental results,where larger aryl groups,which should exhibit stronger CÀH/p interactions with the B(pin) moiety than as imple phenyl group,have ap ositive effect on the enantioselectivity [1-naphtyl (S)-3a:86% ee;phenyl (S)-3h:7 1% ee;T able 2].T he adamantyl moieties not only induce repulsive but also attractive interactions,s uch as London dispersion forces,b etween the adamantyl moieties and the methyl group in TS1. [23] This is also in agreement with the experimental results,which show that bulky alkyl groups have ap ositive effect on the enantioselectivity [Me (S)-3i: 67 % ee; i-Bu (S)-3j:8 0% ee;T able 2].T he efficient combination of ar igid conformation and attractive and repulsive interactions in the complex contributes to the realization of this challenging enantioselective recognition of achiral radical species despite the long distance between the substrate radical carbon center and the boron atom compared to that found in typical transition-metal-mediated reactions (TS1:B-C = 2.89 ,Cu-C = 3.30 ; TS2:B-C = 2.93 ,Cu-C = 3.22 ).…”

Theoretical investigations of Rh‐catalyzed asymmetric 1,4‐addition to enones using planar‐chiral phosphine‐olefin ligands

“…Analysis of the atoms in molecules (AIM) showed that there is a bond critical point between a carbonyl oxygen of the enone and a hydrogen atom of a methyl group of the ligand. Therefore, It is considered that there is a nonclassical sp 3 CH…O interaction in all the TSs which lead 1,4‐adducts . As mentioned, s‐cis and s‐trans conformers can interconvert each other.…”