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?

Chemical Science Pub Date: 2018-02-28 DOI: 10.1039/C8SC00527C

Abstract

Copper-catalyzed asymmetric direct alkynylation of α-ketoesters with terminal alkynes with chiral prolinol–phosphine ligands, most preferably (αR,2S)-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(tBuOH)/TZVPP//DF-BP86-D3(BJ)/SVP] show the occurrence of OH?O/sp3-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.

Graphical abstract: 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
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