Enantiocontrol by assembled attractive interactions in copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes: OH···O/sp 3 -CH···O two-point hydrogen bonding combined with dispersive attractions

• Published in: Chemical science (Cambridge) Vol. 9; no. 14; pp. 3484 - 3493
• Main Authors: Schwarzer, Martin C, Fujioka, Akane, Ishii, Takaoki, Ohmiya, Hirohisa, Mori, Seiji, Sawamura, Masaya
• Format: Journal Article
• Language: English
• Published: England 14.04.2018
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/C8SC00527C

Copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes with chiral prolinol-phosphine ligands, most preferably (α ,2 )-1-(2-dicyclohexylphosphinobenzyl)-α-neopentyl-2-pyrrolidinemethanol, afforded various enantioenriched chiral propargylic tertiary alcohols. Quantum-chemical calculations using the BP86 density functional including Grimme's empirical dispersion correction [DF-BP86-D3(BJ)-PCM( BuOH)/TZVPP//DF-BP86-D3(BJ)/SVP] show the occurrence of OH···O/sp -CH···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 ( -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.