Titanium(III) Chloride-Zinc/Copper Couple1


[7705-07-9]  · Cl3Ti  · Titanium(III) Chloride-Zinc/Copper Couple  · (MW 154.23) (Zn)

[7440-66-6]  · Zn  · Titanium(III) Chloride-Zinc/Copper Couple  · (MW 65.39)

(reagent combination for the production of low-valent titanium which is used for the inter- and intramolecular reductive coupling of carbonyl and dicarbonyl compounds)

Physical Data: see Titanium(III) Chloride and Zinc/Copper Couple.

Solubility: unknown but presumably low in most organic solvents. THF and DME are the favored solvents for reactions involving this reagent combination.

Handling, Storage, and Precautions: the low-valent titanium species produced by reacting TiCl3 with zinc/copper couple is generally made under an argon atmosphere immediately prior to use. The reagent may be pyrophoric and is certainly moisture sensitive.

Reductive Coupling Reactions.1-12

Among the numerous sources of low-valent Titanium used for the reductive couplings of carbonyl compounds, the Ti0 reagent produced by reacting TiCl3 with freshly prepared zinc/copper couple2 is considered the most effective for many intramolecular coupling reactions of dicarbonyls (see, however, Titanium(III) Chloride-Lithium Aluminum Hydride). Up to 22-membered cycloalkenes have been formed by coupling the appropriate open-chain dicarbonyl precursor with this reagent. The reagent has been employed by its originator, McMurry,2 in the key steps of a number of natural product syntheses. For example, such reductive cyclizations have been used in the preparation of humulene (eq 1),3 as well as a 45:55 mixture of helminthogermacrene and b-elemene (eq 2).4 The reagent has also been exploited in the preparation of compactin and mevinolin analogs,5 flexibilene,3a,c some zizaene sesquiterpenes including (±)-isokhusimone,6 as well as verticillene.7

Under thermally mild conditions (<=25 °C), a,o-dials react with a 1:9 mixture of TiCl3:Zn(Cu) in DME to give 6- to 14-membered cyclic pinacols. cis-Pinacols are the major products when 6- to 8-membered rings are produced while trans-pinacols predominate in rings of 10 or more members.8 This type of cyclization has been employed in the synthesis of the 14-membered ring associated with sarcophytol B (eq 3).8b

A range of structurally novel hydrocarbons1 have been prepared using the title reagent, including optically active doubly bridged allenes,9 betweenanenes,10 in-out bicycloalkanes,11 and intracyclic p-systems (eq 4),12 some of which are capable of forming stable metal complexes.

The intermolecular coupling of two molecules of retinal to yield b-carotene (94%) has been effected with the title reagent and, by virtue of the product's use as a yellow food-coloring agent and a source of vitamin A, this efficient titanium-based synthesis is now licensed for use in commercial production.13 Aromatic aldehydes and ketones possessing other potentially reducible groups (such as the acyloxy, methoxy carbonyl, and tosyloxy moieties) give Ti0-induced carbonyl reductive coupling products in high yields when the TiCl3/Zn(Cu) reagent is employed.14

McMurry has now developed15 an optimized procedure for the reductive coupling of dicarbonyls which employs a combination of the solvate TiCl3(DME)1.5 and a Zn(Cu) couple to form the low-valent titanium reagent.

1. (a) Robertson, G. M. COS 1991, 3, 583. (b) Betschart, C.; Seebach, D. C 1989, 43, 39. (c) McMurry, J. E. CRV 1989, 89, 1513. (d) Lenoir, D. S 1989, 883. (e) Pons, J.-M.; Santelli, M. T 1988, 44, 4295. (f) McMurry, J. E. ACR 1983, 16, 405.
2. (a) McMurry, J. E.; Kees, K. L. JOC 1977, 42, 2655. (b) McMurry, J. E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. JOC 1978, 43, 3255.
3. (a) McMurry, J. E.; Matz, J. R.; Kees, K. L. T 1987, 43, 5489. (b) McMurry, J. E.; Matz, J. R. TL 1982, 23, 2723. (c) McMurry, J. E.; Matz, J. R.; Kees, K. L.; Bock, P. A. TL 1982, 23, 1777.
4. McMurry, J. E.; Kocovsky, P. TL 1985, 26, 2171.
5. Anderson, P. C.; Clive, D. L. J.; Evans, C. F. TL 1983, 24, 1373.
6. Wu, Y.-J.; Burnell, D. J. TL 1988, 29, 4369.
7. Jackson, C. B.; Pattenden, G. TL 1985, 26, 3393.
8. (a) McMurry, J. E.; Rico, J. G. TL 1989, 30, 1169. (b) McMurry, J. E.; Rico, J. G.; Shih, Y. TL 1989, 30, 1173.
9. Nakazaki, M.; Yamamoto, K.; Maeda, M.; Sato, O.; Tsutsui, T. JOC 1982, 47, 1435.
10. (a) Marshall, J. A.; Bierenbaum, R. E.; Chung, K.-H. TL 1979, 2081. (b) Marshall, J. A.; Black, T. H.; Shone, R. L. TL 1979, 4737. (c) Marshall, J. A.; Constantino, M.; Black, T. H. SC 1980, 10, 689. (d) Marshall, J. A.; Black, T. H. JACS 1980, 102, 7581.
11. McMurry, J. E.; Hodge, C. N. JACS 1984, 106, 6450.
12. (a) McMurry, J. E.; Haley, G. J.; Matz, J. R.; Clardy, J. C.; Van Duyne, G.; Gleiter, R.; Schäfer, W.; White, D. H. JACS 1986, 108, 2932. (b) McMurry, J. E.; Haley, G. J.; Matz, J. R.; Clardy, J. C.; Mitchell, J. JACS 1986, 108, 515. (c) McMurry, J. E.; Swenson, R. TL 1987, 28, 3209.
13. McMurry, J. E. U.S. Patent 4 225 734 (CA 1976, 85, 63 205w).
14. Castedo, L.; Saá, J. M.; Suau, R.; Tojo, G. JOC 1981, 46, 4292.
15. McMurry, J. E.; Leckta, T.; Rico, J. G. JOC 1989, 54, 3748.

Martin G. Banwell

University of Melbourne, Parkville, Victoria, Australia

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