Asymmetric construction of tetrahedral chiral zinc with high configurational stability and catalytic activity

Chiral metal complexes show promise as asymmetric catalysts and optical materials. Chiral-at-metal complexes composed of achiral ligands have expanded the versatility and applicability of chiral metal complexes, especially for octahedral and half-sandwich complexes. However, Werner-type tetrahedral complexes with a stereogenic metal centre are rarely used as chiral-at-metal complexes because they are too labile to ensure the absolute configuration of the metal centre. Here we report the asymmetric construction of a tetrahedral chiral-at-zinc complex with high configurational stability, using an unsymmetric tridentate ligand. Coordination/substitution of a chiral auxiliary ligand on zinc followed by crystallisation yields an enantiopure chiral-only-at-zinc complex (> 99% ee). The enantiomer excess remains very high at 99% ee even after heating at 70 °C in benzene for one week. With this configurationally stable zinc complex of the tridentate ligand, the remaining one labile site on the zinc can be used for a highly selective asymmetric oxa-Diels-Alder reaction (98% yield, 87% ee) without substantial racemisation.


Synthesis of H2L
The ligand H2L was synthesised via the route shown in the figure below. Figure 7. Synthetic route to H2L.

2-Bromo-6-isopropylaniline (5)
This compound was prepared in a procedure modified from a report in the literature. 1 N-Bromosuccinimide (NBS) was recrystallised from water in prior to use.
The extracts were washed with water (50 mL) and brine (50 mL) and dehydrated over Na2SO4. The volatiles were removed under a reduced pressure. The crude product was purified by silica gel column chromatography twice, using n-hexane/EtOAc and CH2Cl2/EtOAc, respectively, to give 9 as a yellow solid (1.90 g, 78%).
In the NMR spectra, three isomers were observed in the ratio of 1:0.11:0.067. The second isomer would be a rotamer regarding the slow rotation around the biphenyl and phenyl-enaminone linkages. The last isomer would be an imine tautomer. Most signals of the minor isomers could not be located because of overlapping and low intensity. The major isomer showed broadening and changes in the chemical shifts at high concentrations.
In the NMR spectra, three isomers were observed in a ratio of 1:0.20:0.11. These isomers were presumably rotamers arising from the slow rotation around the biphenyl and phenyl-diketimine linkages and the diketimine moiety. The NMR measurement at 343 K showed coalescence of the second and third isomers, and a different ratio of 1:0.26, supporting that these are interchangeable isomers. Several signals of the minor isomers could not be located because of overlapping and low intensity.

Single-crystal X-ray diffraction analysis of rac-[Zn2L2]
A single crystal suitable for measurement was grown by liquid-liquid diffusion of HMDSO into a C6D6 solution.
Crystal data for rac- Colour code: Zn, blue grey; C, grey; N, blue; O, red; F, yellow green; S, yellow.

Single-crystal X-ray diffraction analysis of (SZn)-[ZnL((S)-dpp)]
A single crystal suitable for measurement was grown by liquid-liquid diffusion of HMDSO into a C6H6 solution.
Crystal data for (

Single-crystal X-ray diffraction analysis of (SZn)-[ZnL(NC t Bu)]
A single crystal suitable for measurement was grown by liquid-liquid diffusion of HMDSO into a solution in t BuCN/C6H6 = 1:3.

Single-crystal X-ray diffraction analysis of rac-[ZnL(2)]
A single crystal suitable for measurement was grown by liquid-liquid diffusion of n-hexane into a C6D6 solution.

Other reaction procedures
A n-hexane solution of ZnEt2 (1.12 M) was diluted with C6D6 to prepare a 40.0 mM solution for these experiments. Molecular Sieves 4A (MS4A) was dried under vacuum at approximately 450 °C for 5 min.

Time-course study of dynamic asymmetric induction for [ZnL((S)-dpp)]
A valved NMR tube was charged with H2L (
The reaction mixture was left at 70 °C for one week. To the mixture was added a C6D6 solution of (R)-mts (800 mM, 27.5 µL, 5.0 equiv.).

Test of configurational stability of (SZn)-[ZnL(NC t Bu)] in other solvents
A valved NMR tube was charged with (SZn)-[ZnL(NC t Bu)] (2.8 mg, 4.0 µmol) and a given solvent (500 µL). The reaction mixture was left at room temperature for 70 days. The volatiles were removed under reduced pressure and the residue was dissolved in C6D6. To the solution was added a C6D6 solution of (R)mts (800 mM, 25.0 µL, 5.0 equiv.). In the case of i PrOH, a triple amount of the (R)-mts solution was used.
Supplementary Figure 50. 1 H NMR spectrum of (R)-3 (CDCl3, 300 K, 500 MHz). Determination of the absolute configuration of the catalysis product (R)-3 The absolute configuration of the catalysis product major enantiomer, (R)-3, was determined by singlecrystal XRD analyses of two derivatives. For one derivative, the use of enantiopure complex (S)-[ZnL(NC t Bu)] synthesised in this study provided high crystallinity as well as high anomalous dispersion and an internal standard for absolute configuration. The correlation of the crystal structure to the major enantiomer in the catalysis was further supported by HPLC analysis of (R)-3 recovered from the crystals.
For the other derivative, (R)-3 was reduced to improve crystallinity without racemisation. The single-crystal XRD result accorded with R configuration.
The mixture was extracted with DCM, and the extract was dried over Na2SO4. The volatiles were removed under a reduced pressure. The residue was purified by PTLC (eluted with n-hexane/EtOAc = 3:1) to give (R,R)-3' (16.4 mg, 81%, 94% ee). For a reference of HPLC analysis, a racemic product was obtained from