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

Copper-catalyzed asymmetric direct alkynylation of alpha-ketoesters with terminal alkynes with chiral prolinol-phosphine ligands, most preferably (alpha R, 2S)-1-(2-dicyclohexylphosphinobenzyl)-alpha-neopentyl-2-pyrrolidinemethanol, afforded various enantioenriched chiral propargylic tertiary alcohols. Quantumchemical calculations using the BP86 density functional including Grimme's empirical dispersion correction [DF-BP86-D3(BJ)-PCM(tBuOH)/TZVPP//DF-BP86-D3(BJ)/SVP] show the occurrence of OH center dot center dot center dot O/sp(3)-CH center dot center dot center dot O two-point hydrogen bonding between the chiral ligand and the carbonyl group of the ketoester in the stereo-determining transition states. Combined with the hydrogen-bonding interactions orienting the ketoester substrate, dispersive attractions between the chiral ligand (P-cyclohexyl groups) and the ketoester in the favored transition states, rather than steric repulsions in the disfavored transition state explain the enantioselectivity of the asymmetric copper catalysis.