Titanium(IV) Chloride-Zinc

TiCl4-Zn
(TiCl4)

[7550-45-0]  · Cl4Ti  · Titanium(IV) Chloride-Zinc  · (MW 189.68) (Zn)

[7440-66-6]  · Zn  · Titanium(IV) Chloride-Zinc  · (MW 65.39)

(combination of reagents which generates a divalent titanium chloride species: an oxophilic reducing agent used for carbonyl couplings1 and reduction of sulfoxides,2 etc.)

Physical Data: see Titanium(IV) Chloride and Zinc.

Solubility: TiCl4: sol aromatic hydrocarbons, ether, THF, dioxane, chlorohydrocarbons. Zinc: insol organic solvents.

Form Supplied in: TiCl4: colorless liquid, or as a crystalline complex with THF; also supplied as solutions in toluene or dichloromethane. Zinc: metallic grey powder.

Preparative Methods: zinc powder (3 equiv) is added slowly to a mixture of the reagent(s) and TiCl4 (1.5 equiv) in THF at -10 °C under argon. The mixture is then heated to the required temperature for an appropriate time.

Handling, Storage, and Precautions: TiCl4 is corrosive and moisture sensitive. Zinc powder will react with water, liberating flammable gases and may spontaneously ignite in air. TiCl2 is moisture and oxygen-sensitive and all reagents and reaction mixtures should therefore be handled under a dry inert atmosphere. Solvents should be dried before use.

Coupling of Aldehydes and Ketones.

Mukaiyama et al. reported that the reagent can be used to effect pinacol couplings (THF, rt, 2 h) or, under more forcing conditions, to give alkenes (THF or dioxane, reflux, >4 h; McMurry coupling).1 When aldehydes or nonsymmetrical ketones are coupled, the stereochemistry about the new double bond is predominantly (E) (eq 1).

Alicyclic ketones are also coupled in high yields, although longer reaction times are required (eq 2).3

Intramolecular couplings have been used to prepare cembrane-type diterpenes,4,5 e.g. isosarcophytol A (eq 3), thiophenes,6 and 2,5-dihydrothiophenes (eq 4).7

Other Reductive Coupling Reactions.

Ketones have been shown to couple intramolecularly with esters,8 imines,9 and nitro groups.9 Aryl ketones give moderate yields of benzofurans (eq 5); aryl substituents in the 2-position of the furan are advantageous. Coupling with imines is analogous to the pinacol coupling, giving 2-aminoethanols (eq 6). The reaction with nitro groups affords cyclic imines and has been used to effect a reasonable synthesis of some diarylpyrrolines (eq 7).

Benzonitriles are coupled to give 1,2-diarylethanones in moderate yield,10 while alicyclic dinitriles separated by 3-5 atoms gives pyrazolines in modest yield (eq 8).11 Aryl aldoximes and ketoximes give 1,2-diamino compounds in low yields.12

Alkene Synthesis.

The action of TiCl4/Zn/dihaloalkanes is discussed in Titanium(IV) Chloride. As well as converting 1,2-diols to alkenes (see above), b-hydroxy phenyl sulfides (eq 9),13,14 b-hydroxy pyridyl sulfides (eq 10),14 and b-benzoyloxy sulfides (eq 11)15 undergo reductive elimination to give alkenes. To achieve good yields, either pyridine is used as solvent or an amine is added to the reaction mixture. In the latter case, good yields of exo-methylene compounds can be obtained. However, more direct methods, e.g. Wittig or Tebbe, are preferred.

Phenyl vinyl sulfides may be obtained from b-hydroxy thioacetals14 or from a-halo-b-hydroxy sulfoxides,16 while a,a-dichloro sulfoxides give the chloroalkene (eq 12).16

Excellent yields of alkenes are obtained from 1,2-dibromo compounds when treated with zinc and catalytic amounts of TiCl417 via a trans-stereoselective reductive elimination (eqs 13 and 14).

Deoxygenations.

Heteroaromatic amine oxides are reduced to the corresponding nitrogen-containing heteroaromatic system,18 sulfoxides to sulfides (eq 15),2 and triphenylarsine oxide to triphenylarsine,19 all in good to excellent yields. The reduction of sulfoxides proceeds more rapidly and under less extreme conditions than those for Titanium(III) Chloride.

Difluoromethylaldol Condensations.

Zinc and catalytic quantities of TiCl4 react with chlorodifluoromethyl ketones and ketones or aldehydes to give the aldol products (eq 16).20 Yields are moderate to good, but poor when the electrophile is an enone, enal, or aromatic carbonyl.

Simple a-chloro ketones undergo erythro-selective aldol reactions,20 but the yields and selectivities do not reach the levels expected for controlled aldol condensations.


1. Mukaiyama, T.; Sato, T.; Hanna, J. CL 1973, 1041.
2. Drabowicz, J.; Mikolajczyk, M. S 1978, 138.
3. Tolstikov, G. A.; Lerman, B. M.; Belogaeva, T. A. SC 1991, 21, 877.
4. Li, Y.; Li, W.; Li, Y. TL 1992, 33, 1225.
5. Li, Y.; Li, W.; Li, Y. SC 1992, 22, 817.
6. Nakayama, J.; Machida, H.; Saito, R.; Hoshino, M. TL 1985, 26, 1983.
7. Nakayama, J.; Machida, H.; Hoshino, M. TL 1985, 26, 1981.
8. Banerji, A.; Nayak, S. K. CC 1990, 150.
9. Chen, W. X.; Jiang, J. P.; Goa, J.; Chen, J. X.; Shen, W. B. Chin. Chem. Lett. 1991, 2, 439.
10. Chen, W. X.; Chen, J. X.; Jiang, J. P.; Kao, T. Y. Chin. Chem. Lett. 1991, 2, 351.
11. Chen, J. X.; Jiang, J. P.; Chen, W. X.; Kao, T. Y. H 1991, 32, 2339.
12. Hu, M.; Xi, S.; Sheng, W.; Gu, X.; Chen, W. Nanjing Daxue Xuebao Zinan Kexue 1992, 28, 88 (CA 1993, 118, 59 344).
13. Song, S.; Shiono, M.; Mukaiyama, T. CL 1974, 1161.
14. Mukaiyama, T.; Shiono, M.; Sato, T. CL 1974, 37.
15. Mukaiyama, T.; Watanabe, Y.; Shiono, M. CL 1974, 1523.
16. Reutrakul, V.; Poochaivatananon, P. TL 1983, 24, 531.
17. Sato, F.; Akiyama, T.; Iida, K.; Sato, M. S 1982, 1025.
18. Homaidan, F. R.; Issidorides, C. H. H 1981, 16, 411.
19. Xing, Y. D.; Hou, X. L.; Huang, N. Z. TL 1981, 22, 4727.
20. Ishihara, T.; Yamanaka, T.; Ando, T. CL 1984, 1165.

Ian C. Richards

AgrEvo, Saffron Walden, UK



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