**3. One-step templated synthesis of chiral organometallic salicyloxazoline complexes**

Chiral oxazolinyl organometallic complexes are very important catalysts in organic chemistry [14–22]. Several organometallic complexes containing 2-(2′-hydroxyphenyl) oxazolines are reported in the literature [23–42]. The general approach to the synthesis of metal complexes begins with ligand synthesis, followed by ligand reaction with metal salts to afford organometallic complexes [43].

In 2017, our research group first reported a one-pot multicomponent synthesis of chiral oxazolinyl-zinc complexes [44] in the presence of a large amount of ZnCl2 (0.4–2.6 eq.); the yields of certain products reached 90%. Herein, the chiral salicyloxazoline metal complexes **16–23** can be obtained by using 1.0 eq. of metal salts such as copper, cobalt, nickel, manganese, palladium, and platinum salts as the third component. The structures of these complexes were characterized by X-ray crystallography. The results prove that organometallic complexes can be assembled with two reactants and different amounts of metal salts.

Chiral bis(oxazoline) copper complex **16**, nickel complex **17**, cobalt complex **18**, and palladium complex **19** were generated as crystals with the chemical formula ML2 (L = 2-(4-R1–4,5-dihydrooxazol-2-yl)phenol, R1: d-Ph, M: Cu, Ni, Co; R1: l-CH2Ph; M: Pd). The syntheses of these complexes can be summarized as follows: A mixture of 2-hydroxybenzonitrile and d-phenylglycinol or l-phenylalaninol in 50 mL of chlorobenzene was refluxed for 72 h with 1.0 eq. of each of the above appropriate metal salts. After removal of the chlorobenzene, single crystals of chiral bis(oxazolinyl) metal complexes **16–19** were present after natural evaporation of the recrystallization or chromatographic solvent with petroleum and dichloromethane (**Figure 22**).

In **Figures 23** and **24**, refluxing a mixture of 2-cyanophenol and d-phenylglycinol in chlorobenzene for 72 h with 1.0 eq. of cobalt chloride hexahydrate or 1.0 eq. of cobalt acetate tetrahydrate, respectively, afforded complexes **20** and **21**. Further, through slow evaporation from a 1:1 mixture of ethanol and chloroform, crystals of complex **20** were obtained. However, the crystals of complex **21** were present after column separation with a 4:1 solution of petroleum ether and dichloromethane, followed by evaporation of the volatile components.

Notably, the product complexes **18** and **20** were obtained using CoCl2·6H2O as a reagent with different solvents in the workup procedure. As seen in **Figure 23**, when a nonpolar solvent, such as petroleum ether or n-hexane, was used in the recrystallization medium, crystals of complex **18** were obtained. However, if the recrystallization was carried out with a mixture of two polar solvents, such as ethanol and chloroform, crystals of complex **20** were obtained.

Similarly, in the synthesis of chiral oxazoline manganese complex **22** by the title method, 2-hydroxybenzonitrile and d-phenylglycinol were refluxed with 1.0 eq. of manganese acetate tetrahydrate in chlorobenzene for 60 h (**Figure 24**). After removal of the chlorobenzene and slow evaporation with a mixture of absolute ethanol and chloroform, crystals of complex **22** were obtained.

Interestingly, in **Figure 25**, when employed by 1.0 eq. of PtCl2 in the reaction of 2-hydroxybenzonitrile with D-phenylglycinol in chlorobenzene, the crystal structure of the resulting Pt complex was different from the aforementioned complexes **16–22** (**Figures 26**–**32**); a complex containing

**37**

**Figure 25.**

**Figure 23.**

**Figure 24.**

*One-Pot Synthesis of Chiral Organometallic Complexes DOI: http://dx.doi.org/10.5772/intechopen.89865*

*Solvent effects on the formation of complexes 18 and 20.*

*One-pot synthesis of tri(oxazoline) metal complexes 21 and 22.*

*One-pot synthesis of oxazoline platinum complex 23.*

**Figure 22.** *Templated synthesis of complexes 16–19.*

*Synthesis Methods and Crystallization*

In 2017, our research group first reported a one-pot multicomponent synthesis of chiral oxazolinyl-zinc complexes [44] in the presence of a large amount of ZnCl2 (0.4–2.6 eq.); the yields of certain products reached 90%. Herein, the chiral salicyloxazoline metal complexes **16–23** can be obtained by using 1.0 eq. of metal salts such as copper, cobalt, nickel, manganese, palladium, and platinum salts as the third component. The structures of these complexes were characterized by X-ray crystallography. The results prove that organometallic complexes can be assembled

Chiral bis(oxazoline) copper complex **16**, nickel complex **17**, cobalt complex **18**, and palladium complex **19** were generated as crystals with the chemical formula ML2 (L = 2-(4-R1–4,5-dihydrooxazol-2-yl)phenol, R1: d-Ph, M: Cu, Ni, Co; R1: l-CH2Ph; M: Pd). The syntheses of these complexes can be summarized as follows: A mixture of 2-hydroxybenzonitrile and d-phenylglycinol or l-phenylalaninol in 50 mL of chlorobenzene was refluxed for 72 h with 1.0 eq. of each of the above appropriate metal salts. After removal of the chlorobenzene, single crystals of chiral bis(oxazolinyl) metal complexes **16–19** were present after natural evaporation of the recrystallization or chromatographic solvent with petroleum and dichloromethane (**Figure 22**). In **Figures 23** and **24**, refluxing a mixture of 2-cyanophenol and d-phenylglycinol in chlorobenzene for 72 h with 1.0 eq. of cobalt chloride hexahydrate or 1.0 eq. of cobalt acetate tetrahydrate, respectively, afforded complexes **20** and **21**. Further, through slow evaporation from a 1:1 mixture of ethanol and chloroform, crystals of complex **20** were obtained. However, the crystals of complex **21** were present after column separation with a 4:1 solution of petroleum ether and dichloromethane,

Notably, the product complexes **18** and **20** were obtained using CoCl2·6H2O as a reagent with different solvents in the workup procedure. As seen in **Figure 23**, when a nonpolar solvent, such as petroleum ether or n-hexane, was used in the recrystallization medium, crystals of complex **18** were obtained. However, if the recrystallization was carried out with a mixture of two polar solvents, such as ethanol and

Similarly, in the synthesis of chiral oxazoline manganese complex **22** by the title method, 2-hydroxybenzonitrile and d-phenylglycinol were refluxed with 1.0 eq. of manganese acetate tetrahydrate in chlorobenzene for 60 h (**Figure 24**). After removal of the chlorobenzene and slow evaporation with a mixture of absolute

Interestingly, in **Figure 25**, when employed by 1.0 eq. of PtCl2 in the reac-

tion of 2-hydroxybenzonitrile with D-phenylglycinol in chlorobenzene, the crystal structure of the resulting Pt complex was different from the aforementioned complexes **16–22** (**Figures 26**–**32**); a complex containing

with two reactants and different amounts of metal salts.

followed by evaporation of the volatile components.

chloroform, crystals of complex **20** were obtained.

ethanol and chloroform, crystals of complex **22** were obtained.

**36**

**Figure 22.**

*Templated synthesis of complexes 16–19.*

**Figure 23.** *Solvent effects on the formation of complexes 18 and 20.*

#### **Figure 24.** *One-pot synthesis of tri(oxazoline) metal complexes 21 and 22.*

**Figure 25.** *One-pot synthesis of oxazoline platinum complex 23.*

**Figure 26.** *The crystal structure of complex 16.*

**Figure 27.** *The crystal structure of complex 17.*

**39**

**Figure 31.**

*The crystal structure of complex 21.*

**Figure 29.**

**Figure 30.**

*The crystal structure of complex 20.*

*The crystal structure of complex 19.*

*One-Pot Synthesis of Chiral Organometallic Complexes DOI: http://dx.doi.org/10.5772/intechopen.89865*

**Figure 28.** *The crystal structure of complex 18.*

*One-Pot Synthesis of Chiral Organometallic Complexes DOI: http://dx.doi.org/10.5772/intechopen.89865*

#### **Figure 29.** *The crystal structure of complex 19.*

*Synthesis Methods and Crystallization*

**Figure 26.**

**Figure 27.**

*The crystal structure of complex 17.*

*The crystal structure of complex 16.*

**38**

**Figure 28.**

*The crystal structure of complex 18.*

#### **Figure 30.** *The crystal structure of complex 20.*

**Figure 31.** *The crystal structure of complex 21.*

**Figure 32.** *The crystal structure of complex 22.*

**Figure 33.**

*The crystal structure of complex 23.*


**41**

*One-Pot Synthesis of Chiral Organometallic Complexes DOI: http://dx.doi.org/10.5772/intechopen.89865*

plexes via a one-step procedure (**Table 2**).

complexes, mononuclear and mutinuclear complexes, etc.

complexes in medical fields is currently being developed.

The authors declare that they have no competing interests.

**Additional information is provided in the article as follows:**

articles/10.1186/s13065-017-0305-1.

(**Figures 25** and **33**).

**4. Conclusions**

**Acknowledgements**

**Conflicts of interest**

**Appendix**

for providing supports and help.

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 ether and dichloromethane (4:1) followed by crystallization via slow evaporation

The proposed mechanism shows that excess metal salts can activate the reaction of 2-hydroxybenzonitrile with D-phenylglycinol in chlorobenzene to form ligand intermediates and then directly furnish the corresponding organometallic com-

One-pot synthesis of oxazolinyl-zinc(II) complexes **1–23** at yields 25–95% was firstly demonstrated by assembling three-component reactions between metal salts, amino alcohols, and a variety of nitrile precursors. From the crystal structures of the complexes **1–23**, the reaction product is highly dependent on the presence of ligands, the amount of metal salts, and the nature of the substituent at the stereogenic center, giving a variety of coordination modes, such as mono- and bis-chelate

Investigations into other oxazolinyl organometallic complexes and the catalytic properties of these complexes as chiral ligands are currently ongoing. These complexes exhibit bioactivities as anticancer reagents, and the future use of these

This work was supported by the Hefei University of Technology and the University of Science and Technology of China. The authors also thank prof. King Kuok (Mimi) from Imperial College London, prof. Peter J. Stang from the University of Utah and prof. K.H. Lee from the University of Carolina at Chapel Hill

1.The characterization spectra of compounds 1–**15** [44] are available free of charge via the Internet at https://ccj.springeropen.com/. The crystallographic information of compounds **1**–**15** are available from the Cambridge Crystallographic Data Center (CCDC) as supplementary publications CCDC 853709–853,710, 931, 745–931,746, 931,745–931,748, 931,751–931,753, 931,756, 1,014,806–1,014,807, and 1,540,756, deposit@ccdc.cam.ac.uk or http://www. ccdc.cam.ac.uk.

2.Supporting information including the NMR spectra for compounds **1–15** [44] are available free of charge via the Internet at https://ccj.springeropen.com/

#### **Table 2.**

*One-pot synthesis of salicyloxazoline complexes.*

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 ether and dichloromethane (4:1) followed by crystallization via slow evaporation (**Figures 25** and **33**).

The proposed mechanism shows that excess metal salts can activate the reaction of 2-hydroxybenzonitrile with D-phenylglycinol in chlorobenzene to form ligand intermediates and then directly furnish the corresponding organometallic complexes via a one-step procedure (**Table 2**).
