Titanium(III) Chloride-Potassium1


[7705-07-9]  · Cl3Ti  · Titanium(III) Chloride-Potassium  · (MW 154.23) (K)

[7440-09-7]  · K  · Titanium(III) Chloride-Potassium  · (MW 39.10)

(combination of reagents used for the in situ generation of highly oxophilic low-valent titanium species2 which are used to effect the reductive coupling of carbonyl groups2 (McMurry coupling) and reductive deoxygenations3)

Physical Data: see Titanium(III) Chloride and Potassium.

Solubility: TiCl3: sol alcohol, hydrochloric acid; v. slightly sol DME, THF. K: insol DME, THF.

Form Supplied in: TiCl3: violet, air-sensitive solid. K: metal under paraffin.

Preparative Methods: potassium metal (3.2 equiv) is washed with hexane and added to a slurry of titanium(III) chloride (1 equiv) in THF at rt under an inert atmosphere. The mixture is heated under reflux for 1 h, during which time the reaction mixture turns black. The mixture is cooled to rt and is then ready for the addition of the reaction substrates.

Handling, Storage, and Precautions: care is required when handling potassium because it reacts violently with water and protic solvents, liberating highly flammable gases which are readily ignited. Titanium(III) chloride should be stored and used under argon, preferably in a glove bag or box. The low-valent titanium reagent is sensitive to air and moisture; therefore to obtain good yields, it must be freshly prepared. All reactions should be performed under argon. If excess reagent is used, it should be quenched prior to workup by the cautious addition of methanol. Alternatively, if the use of methanol is incompatible with the products, the reaction mixture may be filtered carefully through a pad of Celite; care must be taken as the residues collected may be pyrophoric. All solvents must be dried and preferably deoxygenated or degassed before use.

Coupling of Aldehydes and Ketones.

Reduction of TiCl3 with 3 equiv of potassium gives a Ti0 species which is used in the reductive coupling (McMurry coupling) of carbonyl compounds (eq 1). Other less hazardous methods exist for the generation of Ti0, e.g. Titanium(III) Chloride-Zinc/Copper Couple or TiCl3/Li, but the reagent generated from potassium gives the most consistent results and the highest yields when coupling aliphatic aldehydes and ketones.4 When aldehydes or nonsymmetrical ketones are coupled, the (E)-alkene product predominates. Even with the highly hindered 1-methyl-2-adamantanone, coupling could be achieved in 52% yield (eq 2).5 The recently reported generation of Ti0 from the TiCl3(DME)1.5 solvate and Zinc/Copper Couple6 is likely to be the reagent of choice in future. It gives good to excellent yields, while avoiding the hazards associated with the use of potassium.

The mechanism of the McMurry coupling has been studied.7 The reaction proceeds via a pinacol coupling and subsequent deoxygenation. Using the title reagent, it is only possible to isolate good yields of the pinacol product when the formation of the alkene is disfavored, e.g. in compound (1),8 where the double bond would have to be formed at a strained bridgehead (eq 3). A wide range of functionality is compatible with carbonyl coupling,1a although allylic alcohols, epoxides, oximes, sulfoxides, and nitro groups are not.

The reagent has been modified by the use of Potassium-Graphite as the reducing partner,9,10 with the Ti0 being formed on the surface of the graphite. Again, 3 equiv of potassium are generally used, although the cyclization of (2) to (3) was optimized using 2 equiv of potassium (eq 4).11 Formally, this requires a TiI species for the coupling. The reaction was highly specific: no epimerization was noted at C-8a, nor was there any loss of the acetal.

Coupling of Esters and Amides.

The Ti0 on graphite reagent facilitates the intramolecular coupling of ketones to esters,10 yielding enol ethers which subsequently hydrolyze to ketones (eq 5). This type of reaction has also found use in the synthesis of furans and benzofurans by the coupling of O-benzoyl derivatives of 1,3-dicarbonyl compounds (eq 6);12 yields are improved by further aromatic substituents. Indoles may be prepared by analogous methods (eq 7).12


As the McMurry coupling proceeds via the pinacol, it is not surprising that Ti0 is capable of converting 1,2-diols to alkenes in good to excellent yields. In addition to diols, TiCl3/K also converts 1-phenylthio-2-benzoyloxyethanes to alkenes (eq 8).13 Deoxygenation of phenols and enolizable ketones is achieved via the O-phosphate derivative (eqs 9 and 10).3

Miscellaneous Reductions.

The Ti0 produced by the title reagents can be expected to perform the transformations achieved by Ti0 generated from other reagents, e.g. coupling of thiocarbonyls to alkenes or allylic alcohols to 1,5-dienes. However, in these cases the use of potassium is not justified.

1. (a) McMurry, J. E. CRV 1989, 89, 1513. (b) Lenoir, D. S 1989, 883.
2. McMurry, J. E.; Fleming, M. P. JOC 1976, 41, 896.
3. (a) Welch, S. C.; Walters, M. E. JOC 1978, 43, 2715. (b) Welch, S. C.; Walters, M. E. JOC 1978, 43, 4797.
4. McMurry, J. E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. JOC 1978, 43, 3255.
5. Lenoir, D.; Frank, R. TL 1978, 53.
6. McMurry, J. E.; Lectka, T.; Rico, J. G. JOC 1989, 54, 3748.
7. Davis, R.; Malinowski, M.; Westdorp, I.; Geise, H. T. JOC 1982, 47, 248.
8. Corey, E. J.; Danheiser, R. L.; Candrasekaran, S.; Sinet, P.; Keck, G. E.; Gras, J.-L. JACS 1978, 100, 8031.
9. Boldrini, G. P.; Savoia, D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. JOM 1985, 280, 307.
10. Füstner, A.; Weidmann, H. S 1987, 1071.
11. (a) Clive, D. L. J.; Zhang, C.; Murthy, K. S. K.; Hayward, W. D.; Dangneault, S. JOC 1991, 56, 6447. (b) Clive, D. L. J.; Murthy, K. S. K.; Zhang, C.; Hayward, W. D.; Dangneault, S. CC 1990, 509. (c) Clive, D. L. J.; Murthy, K. S. K.; Wee, A. G. H.; Presad, J. S.; de Silva, G. V. J.; Majewski, M.; Anderson, P. C.; Haugen, R. D.; Heerze, L. D. JACS 1988, 110, 6914.
12. Fürstner, A.; Jumbam, D. N.; Weidmann, H. TL 1991, 32, 6695.
13. Welch, S. C.; Loh, J.-P. JOC 1981, 46, 4073.

Ian C. Richards

AgrEvo, Saffron Walden, UK

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