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.

Martin C Schwarzer,Seiji Mori,Akane Fujioka,Hirohisa Ohmiya,Takaoki Ishii,Masaya Sawamura

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.

Highlights

Steric strain called steric repulsion between catalysts and substrates plays an important role in enantioselective catalysis, while catalyst design utilizing catalyst–substrate secondary attractive interactions such as electrostatic interactions, hydrogen bondings, p/p stackings and C–H/p interactions may produce advanced concepts.[1]
Density functional theory (DFT) calculations indicated the occurrence of two-point hydrogen bonding comprising OH/O and non-classical sp3CH/O hydrogen bonds,[5,6,7] which orient the carbonyl group of the prochiral aldehyde
Copper-catalyzed asymmetric direct alkynylation of a-ketoesters with terminal alkynes to produce enantioenriched chiral propargylic tertiary alcohols has been developed by employing a chiral prolinol–phosphine ligand

Summary

Introduction

Steric strain called steric repulsion between catalysts and substrates plays an important role in enantioselective catalysis, while catalyst design utilizing catalyst–substrate secondary attractive interactions such as electrostatic interactions, hydrogen bondings, p/p stackings and C–H/p interactions may produce advanced concepts.[1]. We report that the copper-catalyzed asymmetric direct alkynylation of a-ketoesters with chiral prolinol–phosphine ligands occurred with a high level of enantioselectivity through a discrimination of two ketoic carbonyl substituents, R1 and CO2R2, by the chiral catalyst.

Results

Conclusion