Titanium1

Ti

[7440-32-6]  · Ti  · Titanium  · (MW 47.88)

(low-valent titanium, i.e. Ti0/TiI, can be generated from a variety of sources and is used for the inter- and intramolecular reductive coupling of carbonyl and dicarbonyl compounds, imines, and iminium species, and for reductive elimination reactions and reductions)

Physical Data: mp 1677 °C; d (a-form) 4.506 g cm-3.

Solubility: unknown but presumably low in most organic solvents. THF and DME appear to be the favored solvents for reactions involving low-valent titanium.

Form Supplied in: a 4:1 ball-milled mixture of TiCl3 and LiAlH4 is available commercially and serves as a precursor to the McMurry reagent (see Titanium(III) Chloride-Lithium Aluminum Hydride). Low-valent titanium can be generated in situ from a variety of other sources as discussed below.

Preparative Methods: low-valent titanium reagents, including Ti0, can be generated by in situ reduction of TiI-TiIV chlorides. At least a dozen commonly used procedures have been reported including those involving TiCl3/Zn,2 TiCl3/Mg,3 TiCl3/LiAlH4,4 TiCl3/K,5 TiCl3/Li,6 TiCl3/Zn(Cu),5 TiCl3/C8K,7 CpTiCl3/LiAlH4,8 TiCl4/Zn,9 TiCl4/Al/AlCl3,8 and TiCl4/Mg(Hg).8,10 Whether a Ti0 or a TiI species is generated is dependent upon various factors, including the particular reagent combination used and the titanium chloride to reductant ratio employed.

Handling, Storage, and Precautions: most commonly, low-valent titanium species are prepared under an inert atmosphere (nitrogen or argon) immediately prior to use. Presumably, the reagent is pyrophoric although this property may be due to the residual reducing agent used in the preparation process and may not be an inherent property of Ti0/TiI itself. The reagent is moisture sensitive.

Inter- and Intramolecular Coupling of Carbonyl and Dicarbonyl Compounds.

The capacity of low-valent titanium species to effect reductive couplings was reported in 1973-1974 by several independent groups,1,3,9 but McMurry and his co-workers have exploited such processes most extensively. A number of excellent reviews1 are available on this and related topics. McMurry has now developed11 an optimized procedure involving a combination of the TiCl3/dimethoxyethane solvate TiCl3(DME)1.5 and Zinc/Copper Couple. Thus coupling of diisopropyl ketone with the TiCl3(DME)1.5/Zn(Cu) reagent gives an 87% yield of the expected alkene (eq 1). A 4:1 ratio of TiCl3(DME)1.5 to carbonyl compound appears to give the best results. When the same conversion is effected using TiCl3/LiAlH4 and TiCl3/Zn(Cu), yields of 12% and 37%, respectively, are obtained. Cross coupling of different carbonyl compounds to produce unsymmetrical alkenes can be effected in acceptable yield if one of the components, often acetone, is used in excess.10 The coupling conditions have proven to be compatible with a variety of other potentially reducible functional groups including carboxylate and sulfonate esters,12 as well as halides.13

Intramolecular couplings of dicarbonyl compounds (including diketones, dialdehydes and keto esters) can be effected very efficiently with low-valent titanium (eq 2) and such processes have been exploited extensively in the synthesis of a number of natural products1 and various novel hydrocarbons1 (see Titanium(III) Chloride-Zinc/Copper Couple for examples).

The geometry (E or Z) about the alkene double bond being formed in these so-called McMurry reactions is apparently controlled by thermodynamic factors. When the energy difference between the (E)- and (Z)-alkenes exceeds 4-5 kcal mol-1 the former isomer is formed preferentially.14 However, coupling of alkyl aryl ketones affords the (Z)-alkene preferentially, perhaps because of p-complexation between the phenyl rings and Ti0.15 The mechanism proposed (eq 3)1,16 to account for these conversions involves initial pinacolic-type coupling followed by successive elimination of 2 equiv of Ti=O to produce the observed products. When short reaction times and low temperatures are used, pinacols can be isolated. If such species are resubjected to the normal coupling conditions, deoxygenation occurs and the expected alkene results. Interestingly, when stereochemically pure pinacols are subjected to reaction with low-valent titanium reagents, then mixtures of (E)- and (Z)-alkenes are produced although some stereochemistry is preserved.1a

The reductive coupling of imines and related iminium species to give vic-diamines can be effected by low-valent titanium species.17-19 In those cases where it is relevant, low to modest diastereoselectivities are observed (eq 4). Allylic alcohols, benzylic alcohols, and benzylic halides all undergo reductive coupling in the presence of certain low-valent titanium reagents (see Titanium(III) Chloride-Lithium Aluminum Hydride).

Reductive Eliminations.

vic-Dibromides,20,21 bromohydrins,22,23 epoxides,22,24-27 hydroxy sulfides,28-30 and allylic diols,31-34 as well as 1,2-diols (pinacols), undergo reductive elimination on exposure to various low-valent titanium species, resulting in the formation of the corresponding alkene or 1,3-alkadiene. The dithioacetals of various acyloins also suffer reductive elimination upon treatment with Ti0, thereby affording vinyl sulfides.35

Reductions.

Various reductions can be effected with Ti0/TiI species. Thus enol phosphates are converted into the corresponding alkenes36 while analogous reduction of aryl phosphates37 provides a useful protocol for the deoxygenation of phenols. Acyl, vinyl, and alkyl halides, as well as dithioacetals, can all be converted into the corresponding hydrocarbon on exposure to various sources of low-valent titanium,38-41 while both nitriles42 and isocyanides43 suffer reductive removal of the -CN and -NC groups, respectively. Reduction (net addition of the elements of H2) of both isolated44-46 and conjugated47,48 double bonds can also be accomplished with low-valent titanium.


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. Lenoir, D. S 1977, 553.
3. Tyrlik, S.; Wolochowicz, I. BSF(2) 1973, 2147.
4. McMurry, J. E.; Fleming, M. P. JACS 1974, 96, 4708.
5. McMurry, J. E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. JOC 1978, 43, 3255.
6. (a) McMurry, J. E.; Fleming, M. P. JOC 1976, 41, 896. (b) Nishida, S.; Kataoka, F. JOC 1978, 43, 1612.
7. (a) Fürstner, A.; Weidmann, H. S 1987, 1071. (b) Fürstner, A.; Csuk, R.; Rohrer, C; Weidmann, H. JCS(P1) 1988, 1729.
8. Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S. JOC 1976, 41, 260.
9. Mukaiyama, T.; Sato, T.; Hanna, J. CL 1973, 1041.
10. Carroll, A. R.; Taylor, W. C. AJC 1990, 43, 1439.
11. McMurry, J. E.; Lectka, T.; Rico, J. G. JOC 1989, 54, 3748.
12. Castedo, L.; Saá, J. M.; Suau, R.; Tojo, G. JOC 1981, 46, 4292.
13. Richardson, W. H. SC 1981, 11, 895. (b) Coe, P. L.; Scriven, C. E. JCS(P1) 1986, 475.
14. Lenoir, D.; Burghard, H. JCR(S) 1980, 396.
15. Leimner, J.; Weyerstahl, P. CB 1982, 115, 3697.
16. Dams, R.; Malinowski, M.; Westdorp, I.; Geise, H. Y. JOC 1982, 47, 248.
17. Betschart, C.; Schmidt, B.; Seebach, D. HCA 1988, 71, 1999.
18. Mangeney, P.; Tejero, T.; Alexakis, A.; Grosjean, F.; Normant, J. F. S 1988, 255.
19. Mangeney, P.; Grosjean, F.; Alexakis, A.; Normant, J. F. TL 1988, 29, 2675.
20. Davies, S. G.; Thomas, S. E. S 1984, 1027.
21. Olah, G. A.; Prakash, G. K. S. S 1976, 607.
22. McMurry, J. E.; Silvestri, M. G.; Fleming, M. P.; Hoz, T.; Grayston, M. W. JOC 1978, 43, 3249.
23. McMurry, J. E.; Hoz, T. JOC 1975, 40, 3797.
24. Schobert, R. AG(E) 1988, 27, 855.
25. Ledon, H.; Tkatchenko, I.; Young, D. TL 1979, 173.
26. McMurry, J. E.; Fleming, M. P. JOC 1975, 40, 2555.
27. Mukaiyama, T.; Saigo, K.; Takazawa, O. CL 1976, 1033.
28. Song, S.; Shiono, M.; Mukaiyama, T. CL 1974, 1161.
29. Mukaiyama, T.; Watanabe, Y.; Shiono, M. CL 1974, 1523.
30. Watanabe, Y.; Shiono, M.; Mukaiyama, T. CL 1975, 871.
31. Solladié, G.; Girardin, A. TL 1988, 29, 213.
32. Solladié, G.; Hamdouchi, C. SL 1989, 66.
33. Walborsky, H. M.; Wüst, H. H. JACS 1982, 104, 5807.
34. (a) Solladié, G.; Girardin, A.; Métra, P. TL 1988, 29, 209. (b) Solladié, G.; Hutt, J. JOC 1987, 52, 3560.
35. Mukaiyama, T.; Shiono, M.; Sato, T. CL 1974, 37.
36. Welch, S. E.,; Walters, M. E. JOC 1978, 43, 2715.
37. Welch, S. E.; Walters, M. E. JOC 1978, 43, 4797.
38. Nelsen, T. R.; Tufariello, J. JOC 1975, 40, 3159.
39. Tyrlik, S.; Wolochowicz, I. CC 1975, 781.
40. Ashby, E. C.; Lin, J. J. JOC 1978, 43, 1263.
41. Mukaiyama, T.; Hayashi, M.; Narasaka, K. CL 1973, 291.
42. van Tamelen, E. E.; Rudler, H.; Bjorklund, C. JACS 1971, 93, 7113.
43. van Tamelen, E. E.; Rudler, H.; Bjorklund, C. JACS 1971, 93, 3526.
44. Ashby, E. C.; Lin, J. J. TL 1977, 4481.
45. van Tamelen, E. E.; Cretney, W.; Klaentschi, N.; Miller, J. S. CC 1972, 481.
46. Chum, P. W.; Wilson, S. E. TL 1976, 15.
47. Blaszczak, L. C.; McMurry, J. E. JOC 1974, 39, 258.
48. Hung, C. W.; Wong, H. N. C. TL 1987, 28, 2393.

Martin G. Banwell

University of Melbourne, Parkville, Victoria, Australia



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