[1271-19-8]  · C10H10Cl2Ti  · Dichlorobis(cyclopentadienyl)titanium  · (MW 248.98)

(used in hydrometalation and reduction; pinacol coupling reagent; carbometalation reagent; deoxygenation reagent; addition to carbonyls; Lewis acid catalyst; alkenation reagent)

Alternate Name: titanocene dichloride.

Physical Data: mp 289 °C; d 1.600 g cm-3.

Solubility: sol toluene, chloroform, alcohol, and other hydroxylic solvents; sparingly sol water, petroleum ether, benzene, ether, carbon disulfide, carbon tetrachloride.

Form Supplied in: purple solid; commercially available.

Preparative Methods: see Wilkinson and Birmingham2a and Clearfield et al.2b

Handling, Storage, and Precautions: moisture sensitive; irritant; combustible.

Hydromagnesiation of Alkenes and Alkynes.3

Hydromagnesiation of alkynes, where metal hydride addition occurs with syn stereochemistry, can be carried out with i-BuMgCl and 1-10 mol % of Cp2TiCl2 (eq 1).4 Eq 2 illustrates the hydromagnesiation product of a silylalkyne formed after equilibration, where the C-Mg bond is formed a to the silyl unit (or aryl group with aryl alkylalkynes)5 and syn to the magnesium alkoxide (presumably because of heteroatom-metal coordination).6 The carbon-metal bond may then be used in reactions with a variety of electrophiles (e.g. ketones, alkyl or allyl halides).7 The synthesis of dihydrojasmone represents one of the applications of titanium-catalyzed hydromagnesiation.7a

Hydromagnesiation of allylic and homoallylic alcohols is catalyzed by Cp2TiCl2 as well; however, this transformation is only operative with monosubstituted alkenes, wherein a primary C-Mg bond is generated (eq 3).8 MgH2 and 5 mol % Cp2TiCl2 have been used in the hydromagnesiation of terminal alkenes (>90% yield).9 In addition, as shown below, Cp2TiCl2 catalyzes the hydrometalation of conjugated dienes to afford allyl Grignard reagents, which may then be utilized for further functionalization (eq 4).10

Hydroalumination of Alkenes.

Cp2TiCl2 is an effective catalyst for hydroalumination of mono- and disubstituted alkenes (representative aluminum hydrides: Bis(diisopropylamino)aluminum Hydride and Lithium Aluminum Hydride).11

Hydrogenation Catalysts.

Titanocene dialkyls (formed by the addition of alkyllithiums to Cp2TiCl2) are effective alkene hydrogenation catalysts. Catalytic activity is enhanced when polymer-supported titanocene is used.12

Reduction of Carbonyls.

As shown in eqs 5 and 6, in the presence of 1-3 mol % of Cp2TiCl2, i-BuMgCl is an effective carbonyl-reducing agent.13 Carboxylic acids and esters are reduced to aldehydes14 and alcohols,15 respectively. When methyl and ethyl Grignard reagents are employed, competing direct alkylation occurs. The proposed reducing agent is Cp2TiH, and the reaction is most effective with saturated carbonyls. Aryl and benzylic acids are suitable substrates, whereas a,b-unsaturated acids are recovered unchanged.

Reduction of Bromides.

Treatment of vicinal dibromides with 2 equiv of Cp2TiCl2 and excess Zinc affords the corresponding alkene in high yield (eq 7).16 Alternatively, Cp2TiCl2 may be used catalytically (20 mol %) but longer reaction times are required. Stoichiometric amounts of Cp2TiCl2 and i-PrMgCl effect coupling of allylic and benzylic bromides (eq 8) and debromination of a-bromo ketones (eq 9).17 In addition, debromination of aryl and vinyl bromides proceeds selectively and quantitatively in the presence of catalytic amounts of Cp2TiCl2 (2-5 mol %) and excess i-PrMgCl (eq 10).18 The proposed mechanism involves insertion of Cp2TiH into the carbon-bromine bond, followed by reductive elimination of the product alkene.

Pinacol Coupling Reactions.

Stereoselective pinacol coupling reactions can be effected by a complex derived from Cp2TiCl2 and s-BuMgCl19 or Magnesium.20 Coupling of aromatic and a,b-unsaturated aldehydes typically provides >90% yield and >50:1 threo:erythro (eq 11), whereas saturated aldehydes are unreactive. Pinacol coupling with diaryl ketones has also been achieved;21 the reaction is stoichiometric in Cp2TiCl2 and the active organometallic agent is believed to be a TiIII species.

Carbometalation Reactions.

As shown in eq 12, reaction of syn-1,2-dimethyltitanacyclobutane with I2 affords the corresponding alkyl iodide; subsequent intramolecular carbometalation affords syn-1,2-dimethylcyclopropane stereoselectively.22 Reaction of Cp2TiCl2 with Trimethylaluminum, Dimethylaluminum Chloride, or Diethylaluminum Chloride and silyl alkynes23 proceeds smoothly (25 °C, 2 h) to afford a carbon-metal bond a to the silyl group (eq 13).24 Similar reactions with terminal alkenes afford 1,1-disubstituted alkenes (eq 14).25 As shown in eq 15, selective formation of five- and six-membered ring carbocycles may be accomplished through an alkene or alkyne insertion into a carbon-titanium bond.26

Cyclization of diynes and enynes to five- and six-membered rings has been effected by dibutyltitanocene (eq 16).27 Such cyclization reactions are stoichiometric in Ti and may not be extended to dienes. As shown in eq 17, treatment of an epoxide with Cp2TiCl (from Cp2TiCl2 and Zn powder) in the presence of an alkene results in alkene alkylation. This reaction has been carried out inter-28 and intramolecularly.29 The levels of stereocontrol for the intermolecular reactions are generally low (~2:1). Cp2TiCl2 and i-PrMgBr catalyze the intramolecular cyclization reaction of 1,5-dienes (eq 18;30 these transformations proceed only when the two alkenes are monosubstituted.

Deoxygenation Reactions.

As shown in eqs 19 and 20, treatment of aldehydes, esters, and epoxides with Cp2TiCl2 (10 equiv, pretreated with Na sand) affords deoxygenated adducts in good yields.31 The titanocene reagent is ineffective when alcohols, alkoxides, or acyclic ethers are employed as substrates. A complementary reductive deoxygenation for diaryl and aryl alkyl ketones and alcohols has also been reported (eq 21).32

Cp2TiCl cleaves epoxides by a radical mechanism, affording the regiochemistry opposite to that obtained from the corresponding nucleophilic epoxide opening. In addition, as illustrated in eq 22, depending on the reaction conditions, various epoxides may either be regioselectively converted to the alcohol, or reduced to the derived alkenes.33

Addition of Alkyl Titanocenes to Carbonyls.

Alkylation of aldehydes and ketones with p-allyltitanium complexes (stoichiometric, eq 23) formed from Cp2TiCl2 and various dienes (see eq 4) affords anti homoallylic alcohols selectively.34 Such p-allyltitanium reagents do not react with esters or alkyl halides. Similar alkylation reactions have been carried out with trimethylsilyl35 and 1,3-disubstituted allyl anions.36 Addition to aldehydes (eq 24) followed by hydroxy-silyl elimination yields cis,trans or trans,trans alkenes (basic or acidic conditions, respectively).

Lewis Acid Catalysis with Titanocene Derivatives.37

[Cp*2Ti(H2O)2](CF3SO3)2, a readily made derivative of Cp*2TiCl2,38 is an effective catalyst (1%) for Diels-Alder cycloadditions (eq 25); these cycloadditions may be carried out in the presence of water. Cp2Ti(CF3SO3)2 (made from Cp2TiCl2 and Silver(I) Trifluoromethanesulfonate catalyzes aldol reactions as well.39

Alkenation Reactions.

Me3Al addition to Cp2TiCl2 affords an Al-Ti bimetallic complex (Tebbe's reagent, see m-Chlorobis(cyclopentadienyl)(dimethylaluminum)-m-methylenetitanium) which has been used for methylenation of ketones, esters (eq 26), and alkenes.40 A variety of alkyl groups have been used on titanium to achieve similar alkenations.41

Titanocene dichloride reacts with CH2(MgBr)2 to yield a magnesium analog of Tebbe's reagent; the Mg complex is used to convert alkenes and alkynes to the derived titanacyclobutanes and -butenes, respectively.42 The combination of alkenation of carbonyls and formation of titanacyclobutanes leads to the synthesis of substituted allenes (eq 27), where stoichiometric amounts of the titanacyclobutane are utilized.43 Titanacyclobutane has been shown to serve as a catalyst for ring opening metathesis polymerization reactions.44

Nitrogen fixation reactions have been accomplished with various titanocene systems. For example, titanocene-benzyne complexes react with molecular nitrogen to provide aniline and NH3, albeit in low yield.45

1. For a recent discussion of chemistry of chiral titanocene complexes, see: (a) Halterman, R. L. CRV 1992, 92, 965. For a discussion of chemistry of noncyclopentadienyl Ti complexes, see: (b) Duthaler, R. O.; Hafner, A. CRV 1992, 92, 807. For a review of low valent Ti complexes (carbonyl coupling), see: (c) McMurry, J. E. CRV 1989, 89, 1513. For Cp2TiCl2 and Et2AlCl catalysis of Ziegler-Natta type polymerizations, see: (d) Benedek, I. Stud. Cercet. Chim. 1973, 21, 263. For general references to Ti-mediated or -catalyzed reactions, see: (e) Sato, F. Fundamental Research in Homogeneous Catalysis; Plenum: New York, 1978, vol. 2, p 81. (f) Pearson, A. J. Metallo-Organic Chemistry; Wiley: Chichester, 1985. (g) Wailes, P. C.; Coutts, R. S. P.; Weigold, H. Organometallic Chemistry of Titanium, Zirconium and Hafnium; Academic: New York, 1974.
2. (a) Wilkinson, G.; Birmingham, J. M. JACS 1954, 76, 4281. (b) Clearfield, A.; Warner, D. K.; Molina, C. H. S.; Ropal, R.; Bernal, I. CJC 1975, 53, 1622.
3. For a review on hydromagnesiation reaction, see: Sato, F. JOM 1985, 285, 53.
4. (a) Sato, F.; Ishikawa, H.; Watanabe, H.; Miyake, T.; Sato, M. CC 1981, 718. (b) Dzhemilev, U. M.; Vostrikova, O. S.; Sultanov, R. M.; Gimaeva, A. R. IZV 1988, 9, 2156; BAU 1988, 1936.
5. Sato, F.; Ishikawa, H.; Sato, M. TL 1981, 22, 85.
6. Sato, F.; Watanabe, H.; Tanaka, Y.; Sato, M. CC 1982, 1126.
7. (a) Ito, T.; Okamoto, S.; Sato, F. TL 1990, 31, 6399. (b) Sato, F.; Watanabe, H.; Tanaka, Y.; Yamaji, T.; Sato, M. TL 1983, 24, 1041. (c) Sato, F.; Katsuno, H. TL 1983, 24, 1809. (d) Sato, F.; Kanbara, H.; Tanaka, Y. TL 1984, 25, 5063.
8. Eisch, J. J.; Galle, J. E. JOM 1978, 160, C8.
9. Ashby, E. C.; Smith, T. CC 1978, 30.
10. (a) Sato, F.; Ishikawa, H.; Sato, M. TL 1980, 21, 365. (b) Martin, H. A.; Jellinek, F. JOM 1968, 12, 149. (c) Akutagawa, S.; Otsuka, S. JACS 1975, 97, 6870.
11. (a) Ashby, E. C.; Noding, S. A. TL 1977, 4579. (b) Ashby, E. C.; Noding, S. A. JOC 1979, 44, 4364. (c) Ashby, E. C.; Noding, S. A. JOC 1980, 45, 1035. (d) Attempts to hydrometallate alkenes with other metal hydrides such as LiH and NaH were less successful: Ashby, E. C.; Noding, S. A. JOC 1980, 45, 1041.
12. Bonds, Jr.; W. D.; Brubacker, Jr.; C. H.; Chandrasekaran, E. S.; Gibbons, C.; Grubbs, R. H.; Kroll, L. C. JACS 1975, 97, 2128.
13. Sato, F.; Jinbo, T.; Sato, M. TL 1980, 21, 2171.
14. (a) Sato, F.; Jinbo, T.; Sato, M. S 1981, 871. (b) Berk, S. C.; Kreutzer, K. A.; Buchwald, S. L. JACS 1991, 113, 5093.
15. Sato, F.; Jinbo, T.; Sato, M. TL 1980, 21, 2175.
16. Davies, S. G.; Thomas, S. E. S 1984, 1027.
17. Yanlong, Q.; Guisheng, L.; Huang, Y.-Z. JOM 1990, 381, 29.
18. Colomer, E.; Corriu, R. JOM 1974, 82, 367.
19. Handa, Y.; Inanaga, J. TL 1987, 28, 5717.
20. Schobert, R. AG(E) 1988, 27, 855.
21. Zhang, Y.; Liu, T. SC 1988, 18, 2173.
22. Ho, S. C. H.; Straus, D. A.; Grubbs, R. H. JACS 1984, 106, 1533.
23. (a) Eisch, J. J.; Manfre, R. J.; Komar, D. A. JOM 1978, 159, C13. (b) Van Horn, D. E.; Valente, L. F.; Idacavage, M. J.; Negishi, E.-I. JOM 1978, 156, C20. (c) Snider, B. B.; Karras, M. JOM 1979, 179, C37.
24. Brown, D. C.; Nichols, S. A.; Gilpin, A. B.; Thompson, D. W. JOC 1979, 44, 3457.
25. Barber, J. J.; Willis, C.; Whitesides, G. M. JOC 1979, 44, 3603.
26. (a) Rigollier, P.; Young, J. R.; Fowley, L. A.; Stille, J. R. JACS 1990, 112, 9441. (b) Young, J. R.; Stille, J. R. JACS 1992, 114, 4936. (c) Harms, A. E.; Stille, J. R. TL 1992, 33, 6565. (d) Young, J. R.; Stille, J. R. OM 1990, 9, 3022.
27. (a) Nugent, W. A.; Calabrese, J. C. JACS 1984, 106, 6422. (b) Nugent, W. A.; Thorn, D. L.; Harlow, R. L. JACS 1987, 109, 2788. (c) RajanBabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan, P. J. JACS 1988, 110, 7128. (d) Grossman, R. B.; Buchwald, S. L. JOC 1992, 57, 5803.
28. Nugent, W. A.; RajanBabu, T. V. JACS 1988, 110, 8561.
29. RajanBabu, T. V.; Nugent, W. A. JACS 1989, 111, 4525.
30. Lehmkuhl, H.; Tsien, Y.-L. CB 1983, 116, 2437.
31. van Tamelen, E. E.; Gladysz, J. A. JACS 1974, 96, 5290.
32. Eisch, J. J.; Liu, Z.-R.; Boleslawski, M. P. JOC 1992, 57, 2143.
33. (a) RajanBabu, T. V.; Nugent, W. A.; Beattie, M. S. JACS 1990, 112, 6408. (b) Schobert, R. AG(E) 1988, 27, 855.
34. (a) Sato, F.; Iijima, S.; Sato, M. TL 1981, 22, 243. (b) Sato, F.; Iida, K.; Iijima, S.; Moriya, H.; Sato, M. CC 1981, 1140. (c) Kobayashi, Y.; Umeyama, K.; Sato, F. CC 1984, 621.
35. Sato, F.; Suzuki, Y.; Sato, M. TL 1982, 23, 4589.
36. Sato, F.; Uchiyama, H.; Iida, K.; Kobayashi, Y.; Sato, M. CC 1983, 921.
37. (a) Hollis, T. K.; Odenkirk, W.; Robinson, N. R.; Whelan, J.; Bosnich, B. T 1993, 49, 5415. (b) Hollis, T. K.; Robinson, N. P.; Whelan, J.; Bosnich, B. TL 1993, 34, 4309.
38. Thewalt, U.; Honold, B. JOM 1988, 348, 291.
39. Hollis, T. K.; Robinson, N. P.; Bosnich, B. TL 1992, 33, 6423, and references therein.
40. (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. JACS 1978, 100, 3611. (b) Tebbe, F. N.; Parshall, G. W.; Ovenall, D. W. JACS 1979, 101, 5074. (c) Tebbe, F. N.; Harlow, R. L. JACS 1980, 102, 6149. (d) Pine, S. H.; Zahler, R.; Evans, D. A.; Grubbs, R. H. JACS 1980, 102, 3270. (e) Howard, T. R.; Lee, J. B.; Grubbs, R. H. JACS 1980, 102, 6876. (f) Cannizzo, L. F.; Grubbs, R. H. JOC 1985, 50, 2386. (g) Eisch, J. J.; Piotrowski, A. TL 1983, 24, 2043. (h) Stevenson, J. W. S.; Bryson, T. A. TL 1982, 23, 3143.
41. (a) Petasis, N. A.; Bzowej, E. I. JOC 1992, 57, 1327. (b) Petasis, N. A.; Bzowej, E. I. TL 1993, 34, 943.
42. Bruin, J. W.; Schat, G.; Akkerman, O. S.; Bickelhaupt, F. TL 1983, 24, 3935.
43. (a) Buchwald, S. L.; Grubbs, R. H. JACS 1983, 105, 5490. For reactions with acyl chlorides, see (b) Stille, J. R.; Grubbs, R. H. JACS 1983, 105, 1664. (c) Chou, T.-S.; Huang, S.-B. TL 1983, 24, 2169.
44. Grubbs, R. H.; Tumas, W. Science 1989, 243, 907.
45. Shur, V. B.; Berkovitch, E. G.; Vasiljeva, L. B.; Kudryavtsev, R. V.; Vol'pin, M. E. JOM 1974, 78, 127.

Ahmad F. Houri & Amir H. Hoveyda

Boston College, Chestnut Hill, MA, USA

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