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. 2012 Jul 30;17(8):9010-22.
doi: 10.3390/molecules17089010.

Chiral Zn(II)-bisamidine complex as a Lewis-Brønsted combined acid catalyst: application to asymmetric Mukaiyama aldol reactions of α-ketoesters

Ryo Gotoh  1 , Masahiro Yamanaka
Affiliations

Chiral Zn(II)-bisamidine complex as a Lewis-Brønsted combined acid catalyst: application to asymmetric Mukaiyama aldol reactions of α-ketoesters

Ryo Gotoh et al. Molecules. .

Abstract

Focusing on the steric and electronic properties of the resonance-stabilized amidine framework, a cationic metal-bisamidine complex was designed as a conjugated combined Lewis-Brønsted acid catalyst. The chiral Zn(II)-bisamidine catalyst prepared from the 2,2'-bipyridyl derived bisamidine ligand, ZnCl₂, and AgSbF₆ promoted asymmetric Mukaiyama aldol reaction of α-ketoester and α,α-disubstituted silyl enol ether to afford the α-hydroxyester having sequential quarternary carbons in good yield, albeit with low enantioselectivity. Addition of 1.0 equivalent of the fluoroalcohol having suitable acidity and bulkiness dramatically increased the enantioselectivity (up to 68% ee). DFT calculations suggested that this additive effect would be caused by self-assembly of the fluoroalcohol on the Zn(II)-bisamidine catalyst.

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Figures

Figure 1
Figure 1
(a) Schematic concept of Lewis-Brønstedcombined acid catalyst; (b) Double activation by the normal combined acid; (c) Double activation by the conjugated combined acid.
Figure 2
Figure 2
Design of the metal bisamidine complex as a Lewis-Brønstedcombined acid catalyst.
Figure 3
Figure 3
DFT calculations of bisamidine ligand (L), Zn(II)-bisamidine (Zn2+-L), and Zn(II)-bipyridine (Zn2+-Bipy)complexes (B3LYP/LANL2DZ for Zn, 6-31G* for the rest). Bond lengths are shown in Å. NBO charges are shown in italics.
Figure 4
Figure 4
Schematic geometries for the assembled complex models (A–F) of Zn(II)-L3 and α-ketoester with TFE and the relative energies (B3LYP/LANL2DAZ for Zn, 6-31G* for the rest).
Figure 5
Figure 5
DFT calculations for the TFE addition effect in the complex of Zn(II)-L3 and α-ketoester (B3LYP/LANL2DAZ for Zn, 6-31G* for the rest). Bond lengths are shown in Å.
Scheme 1
Scheme 1
Screening of alcohol additives.
Scheme 2
Scheme 2
Zn(II)-L3 catalyzed reaction of 1b and 2 with or without HFIP.
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