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 attractionsElectronic supplementary information (ESI) available: Representative experimental procedures, spectroscopic data, and computational details. See DOI: 10.1039/c8sc00527c

• Main Authors: Schwarzer, Martin C, Fujioka, Akane, Ishii, Takaoki, Ohmiya, Hirohisa, Mori, Seiji, Sawamura, Masaya
• Format: Journal Article
• Language: English
• Published: 04.04.2018
• DOI: 10.1039/c8sc00527c
• ISSN: 2041-6520

Copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes with chiral prolinol-phosphine ligands, most preferably (α R ,2 S )-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( t BuOH)/TZVPP//DF-BP86-D3(BJ)/SVP] show the occurrence of OH O/sp 3 -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 ( 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. A chiral copper catalyst selects enantiofaces by assembled attractive interactions.