One-step templated synthesis of chiral organometallic salicyloxazoline complexes

Background The general approach to the synthesis of metal complexes begins with ligand synthesis, followed by ligand reaction with metal salts to afford organometallic complexes. Our research group first reported a one-pot multicomponent synthesis of chiral oxazolinyl–zinc complexes, in the presence of a large amount of ZnCl2 (0.4–2.6 equiv.), with the yields of some products reaching 90%. Results Our prior strategy was extended to use copper, cobalt, nickel, manganese, palladium or platinum salts as the third component. The one-step method used 1.0 equivalent of a metal salt, such as M(OAc)2·nH2O or MCl2·nH2O (M: Cu, Co, Ni, Pd or Pt, n = 1, 2 or 4), as a reagent to generate chiral salicyloxazoline complexes 1–8 in the reaction of 2-cyanophenol with different d- and l-amino alcohols. Conclusion Complexes 1–8 were obtained using a one-pot method with a sequential strategy. The reaction outcome was demonstrated for three-component reactions between metal salts, amino alcohols and 2-hydroxybenzonitrile to afford organometallic complexes in good yields (65–95%). Electronic supplementary material The online version of this article (10.1186/s13065-019-0565-z) contains supplementary material, which is available to authorized users.


Results and discussion
Chiral bis(oxazoline) copper complex 1, nickel complex 2, cobalt complex 3 and palladium complex 4 were generated as crystals with the chemical formula ML 2 (L = 2-(4-R 1 -4,5-dihydrooxazol-2-yl)phenol, R 1 : d-Ph, M: Cu, Ni, Co; R 1 : l-CH 2 Ph; M: Pd). The syntheses of these complexes are described below. A mixture of 2-hydroxybenzonitrile and d-phenylglycinol or l-phenylalaninol in 50 mL of chlorobenzene was refluxed for 72 h with 1.0 equiv. of the appropriate metal salt. After removal of chlorobenzene, purification was performed by recrystallization or column chromatography separation with petroleum ether and dichloromethane. Natural evaporation of the recrystallization or chromatographic solvent provided single crystals of chiral bisoxazolinyl  Figures S1-S4).

BMC Chemistry
The chiral oxazoline cobalt complexes 5 and 6 were prepared by refluxing a mixture of 2-cyanophenol and d-phenylglycinol in chlorobenzene for 72 h with 1.0 equiv. of cobalt chloride hexahydrate or 1.0 equiv. of cobalt acetate tetrahydrate, respectively (Schemes 2 and 3, respectively). Crystals of complex 5 were obtained by slow evaporation from a 1:1 mixture of ethanol and chloroform ( Fig. 1: right). However, the crystals of complex 6 were obtained after column chromatography with a 4:1 solution of petroleum ether and dichloromethane, followed by evaporation of the volatile components ( Fig. 2: left). Notably, the product complexes 3 and 5 were obtained using CoCl 2 as a reagent with different solvents in the workup procedure. When a nonpolar solvent, such as petroleum ether or n-hexane, was used in the recrystallization medium, crystals of complex 3 were obtained. However, if the recrystallization was carried out with a mixture of two polar solvents, such as ethanol and chloroform, crystals of complex 5 were obtained (Scheme 2). Both crystal structures are shown in Fig. 1 (left: complex 3, right: complex 5).
Similarly, in the synthesis of chiral oxazoline manganese complex 7 by the title method, 2-hydroxybenzonitrile and d-phenylglycinol were dissolved in chlorobenzene and refluxed in the presence of 1.0 equiv. of manganese acetate tetrahydrate for 60 h (Scheme 3). Crystals of complex 7 ( Fig. 2: right) were obtained by slow evaporation from a mixture of absolute ethanol and chloroform.
Interestingly, when 1.0 equiv. of PtCl 2 was employed in the reaction of 2-hydroxybenzonitrile with d-phenylglycinol in chlorobenzene, the crystal structure of the resulting Pt complex was different from those obtained with the previously mentioned metal salts. Complex 8, which contains one unit of (R)-2-(4-phenyl-4,5-dihydrooxazol-2-yl)phenol and one unit of d-phenylglycinol, was obtained after column chromatography with petroleum Scheme 3 One-pot synthesis of tri(oxazoline) metal complexes 6 and 7 ether and dichloromethane (4:1) followed by crystallization via slow evaporation (Scheme 4, Fig. 3).
The proposed mechanism indicates that the excess metal salts can activate the reaction of 2-hydroxybenzonitrile with d-phenylglycinol in chlorobenzene to form the ligand intermediates and then directly afford the corresponding organometallic complexes via a one-step procedure. Table 1 lists the summary of the metal salts used, the products obtained, and the percentage yields in the reactions.
In complexes 1-4, the two oxazoline ligands arrange their donor atoms in a trans-planar configuration, and the structure features a four-coordinate metal center in a slightly distorted arrangement. The metal center is coordinated with the nitrogen atoms of the oxazolines and oxygen atom donated from the phenolate. The average length of the metal-N bond in complexes 1-4 are: Pd-N 2.003(7) Å > Co-N 1.983(5) Å > Cu-N 1.952(1) Å > Ni-N 1.893(3) Å, which are the same order as the average metal-O bond lengths for complexes 1-4 (e.g., Pd-O The crystal packing structure of complex 5 exhibits a sandwich-like structure and consists of three complex 3 (cobalt(II) chelates) connected by three Co(II) atoms, which generate 2D supramolecular networks. The molecular structure is depicted in Fig. 1 (right). The three cobalt (II) atoms in complex 5 form a linear trimer with a Co2-Co1-Co3 bond angle of 180°. In addition, the nonbonded Co···Co distances range from 2.823(3) to 2.832(3) Å, and the coordination sphere is different. The phenyl groups exhibit an all-cis arrangement. The central cobalt ion is at a highly symmetric center and coordinated to six hydroxyl oxygen atoms from the phenolates. The Co (1) The molecular structures of complexes 6 and 7 were determined by single-crystal X-ray diffraction analysis. It is important to note that the entire molecule is in the independent part, occupying the general position of the P21/c symmetry group. In the structures of 6 and 7, the O and N atoms from the three phenoxy ligands are coordinated to Co 3+ or Mn 3+ with distorted square planar geometries, and the three ligands lie in the adjacent positions. All coordinated ligands act as chelate-forming agents and close the rings using the metal cation. Due to the Jahn-Teller effect, the axial and equatorial Co-N bonds (1.956 (2) (Fig. 3, left) showed the presence of discrete mononuclear molecules, which were separated by van der Waals distances. The complex exhibits a nearly square-planar geometry with two equatorial nitrogen atoms, one from the oxazoline ring   resulted in an average C-N value of 1.291 Å (range 1.205-1.349 Å) and an average C-O value of 1.347 Å (range 1.304-1.424 Å). All C-N and C-O distances in the reported complexes fall within these expected ranges, and no systematic relationship was observed between the distance and the ligand torsion angle. Some selected bond lengths and angles for all complexes are presented in Additional file 2: Table S1, and some hydrogen bond lengths and angles for complex 8 are also shown in Additional file 2: Table S2.
The X-ray crystal structures of the complexes were determined and are shown in the Additional file 1. In all cases, a distorted tetrahedral geometry is found at the metal(II) ion, and the C=N double bond character of the oxazoline ligand is largely retained in the metal complexes.

General
Unless otherwise stated, 2-hydroxybenzonitrile, d-phenylglycinol, l-phenylalaninol, Cu(OAc) 2 ·H 2 O, and PdCl 2 , PtCl 2 were purchased from Acros, Aldrich, or Fluka (USA). Flash column chromatography was performed using Merck (Kenilworth, NJ, USA) silica gel (60, particle size 0.02-0.03 mm). The 1 H and 13 C NMR spectra were recorded using Bruker (Billerica, MA, USA) AM-500 or AM-600 spectrometers. The chemical shifts are reported in ppm (δ) with the solvent referenced to tetramethylsilane (TMS) as the internal standard (residual CHCl 3 , δ H 7.26 ppm; CDCl 3 , δ c 77 ppm). The following abbreviations were used to designate multiplicities: s = singlet, d = doublet, t = triplet, and m = multiplet. The infrared spectra were recorded on a Mattson Instruments (Madison, WI, USA) Galaxy Series FTIR 3000 spectrometer, and the peaks are reported in cm −1 . Elemental analyses were obtained on an Elemental Analyzer AE-3000. The high-resolution mass spectra (HRMS) were obtained on a Micro GCT-MS (Waters, Rochester, MN, USA) equipped with an electron ionization (EI) ion source. Optical rotations were measured on a WZZ-1 automatic polarimeter with a 2 cm cell and recorded at the sodium d-line.

Bis(ligand) copper (II) chelate (CuL1 2 )
A dry 100 mL Schlenk flask was purged with N 2 and charged with Cu(OAc) 2 ·H 2 O (2.2198 g, 11.14 mmol) or CuCl 2 ·2H 2 O (2.1199 g, 10.64 mmol), 2-cyanophenol (2.3808 g, 19.99 mmol) and d-phenylglycinol (3.8002-4.2003 g). Then, 40 mL of chlorobenzene was added, and the reaction mixture was refluxed for 72 h. After cooling to room temperature, the solvent was removed under reduced pressure, and the residue was dissolved in 15 mL of H 2 O followed by extraction with CH 2 Cl 2 (3 × 20 mL). The combined organic extracts were evaporated to yield a crude green oil, which was purified by column chromatography (petroleum ether/CH 2 Cl 2 , 4/1) to afford the title compound as colorless crystals 1.9553 g in 65% yield or 2.4422 g in 85% yield; m.

PtL1(d-phenylglycinol)Cl
Prepared using the procedure described for compound 1 by refluxing a mixture of dry PtCl 2 (0.9026 g, 3.39 mmol), 2-cyanophenol (1.1959 g, 10.04 mmol) and d-phenylglycinol (4.3023 g). The three components were combined under water-and oxygen-free conditions in a dry 100 mL Schlenk flask. The components were dissolved in 80 mL of dry chlorobenzene, and the reaction mixture was refluxed for 60 h. The solvent was removed under reduced pressure, and the residue was dissolved in 15 mL of H 2 O followed by extraction with dichloromethane (10 × 3 mL). The solvent was removed under vacuum to afford the crude product as a red oil. Further purification was carried out using silica gel