Dichlorotitanium Diisopropoxide1

[762-99-2]  · C6H14Cl2O2Ti  · Dichlorotitanium Diisopropoxide  · (MW 236.962)

(a Lewis acid commonly used for the preparation of chiral titanium complexes;2-5 a highly effective catalyst for Diels-Alder reactions,4 [2 + 2] cycloadditions,4 and carbonyl-ene reactions,5 including asymmetric versions of these processes; reagent for the formation of titanium enolates;6,7 component of catalysts used for the stereoselective additions of cyanide3,8 and allyltin9 nucleophiles to aldehydes2)

Alternate Name: dichlorodiisopropoxytitanium.

Physical Data: crystalline solid.

Solubility: sol CH2Cl2, toluene, and other solvents.

Preparative Method: prepared by adding slowly at rt an equimolar amount of Titanium(IV) Chloride to a hexane solution of Titanium Tetraisopropoxide; following mixing, during which heat is evolved, the mixture is allowed to stand at rt for 6 h and the precipitate is collected and washed with hexane; dibromotitanium diisopropoxide is prepared similarly.10

Purification: recrystallization from hexane, followed by drying under vacuum.11,12

Handling, Storage, and Precautions: corrosive; moisture sensitive; use in a fume hood; can be stored under nitrogen in pure form or in solution.

Preparation of Chiral Titanium Complexes.2-5

A variety of Lewis acid promoted transformations which are mediated by titanium complexes can take place with significant enantiocontrol by incorporating chiral nonracemic alkoxy ligands on titanium. One of the most common titanium sources for the synthesis of these derivatives is the title reagent (1), although Chlorotitanium Triisopropoxide and Titanium Tetraisopropoxide are also used. Usually, the two isopropoxy groups are replaced with a chiral diol either by the azeotropic removal of isopropyl alcohol or by simply mixing (1) and the chiral diol in the presence of 4Å molecular sieves. The latter method has been used successfully in several catalytic asymmetric reactions. Among the most effective catalysts for this purpose are the titanium complexes derived from (1) and (S)- or (R)-1,1-Bi-2,2-naphthol (BINOL) (eq 1)5,12 and TADDOL, a bulky tartrate-derived diol (eq 2).3,4,13

[4 + 2] Cycloadditions.

Even when they are generated in situ, the above titanium complexes are very effective catalysts for the asymmetric Diels-Alder reactions of certain dienes and dienophiles, such as acyloxyoxazolidinones (eq 3).13

Very high enantioselectivity is observed in the Diels-Alder reactions of some chiral dienophiles in the presence of (1) (eq 4).14

The reagent derived from (1) and BINOL is an excellent catalyst for the hetero Diels-Alder reactions of glyoxylates (eq 5).5,15

[2 + 2] Cycloadditions.3,4

The chiral titanium derivative in eq 2 is an efficient catalyst for the asymmetric [2 + 2] cycloadditions of alkynyl,16 allenyl,17 and alkenyl sulfides (eq 6).18

Carbonyl-Ene Reaction.5

The combination of (1) with BINOL (eq 1) is a very effective catalyst for the asymmetric carbonyl-ene reaction of glyoxylates (eq 7).11 The bromo analog of (1) is also effective in this process.11,12 The kinetic resolution of racemic alkenes, the desymmetrization of symmetrical dialkenes, as well as certain intramolecular variants of this reaction,19 proceed with equally high diastereo- and enantioselectivity.5 Similar ene-type products are also obtained during the addition of silyl enol ethers to glyoxylates.20

Titanation of Enolates.

The enolates derived from the imines of a-amino esters in the presence of (1) or Chlorotitanium Triisopropoxide react with a,b-unsaturated carbonyl compounds to form pyrrolidine derivatives.6,21 They also react with aldehydes to form anti-amino alcohol products upon hydrolysis of the intermediate oxazolidines (eq 8).7

Enantioselective Additions to Aldehydes.

The chiral titanium complexes formed in situ from (1) can efficiently catalyze the asymmetric addition of cyanide,3,8 as well as allyltin nucleophiles to aldehydes (eq 9).9

Related Reagents.

(R)-1,1-Bi-2,2-naphthotitanium Diisopropoxide; Chlorotitanium Triisopropoxide.

1. Reviews of organotitanium reagents: (a) Bottrill, M.; Gavens, P. D.; Kelland, J. W.; McMeeking, J. In Comprehensive Organometallic Chemistry; Wilkinson, G., Ed; Pergamon: Oxford, 1982; Vol. 3, p 433. (b) Reetz, M. T. Top. Curr. Chem. 1982, 106, 1. (c) Seebach, D.; Weidmann, B.; Widler, L. In Modern Synthetic Methods; Scheffold, R., Ed.; Wiley: New York, 1983; Vol. 3, pp 217-353. (d) Weidmann, B.; Seebach, D. AG(E) 1983, 22, 31. (e) Reetz, M. T. Organotitanium Reagents in Organic Synthesis; Springer: Berlin, 1986. (f) Ferreri, C.; Palumbo, G.; Caputo, R. COS 1991, 1, 139.
2. Duthaler, R. O.; Hafner, A. CRV 1992, 92, 807.
3. Narasaka, K. S 1991, 1.
4. Narasaka, K. PAC 1992, 64, 1889.
5. Mikami, K.; Terada, M.; Narisawa, S.; Nakai, T. SL 1992, 255.
6. Kanemasa, S.; Uchida, O.; Wada, E.; Yamamoto, H. CL 1990, 105.
7. Kanemasa, S.; Mori, T.; Wada, E.; Tatsukawa, A. TL 1993, 34, 677.
8. Minamikawa, H.; Hayakawa, S.; Yamada, T.; Iwasawa, N.; Narasaka, K. BCJ 1988, 61, 4379.
9. Costa, A. L.; Piazza, M. G.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. JACS 1993, 115, 7001.
10. Dijkgraaf, C.; Rousseau, J. P. G. Spectrochim. Acta, Part A 1968, 24, 1213.
11. Mikami, K.; Terada, M.; Nakai, T. JACS 1990, 112, 3949.
12. Mikami, K.; Terada, M.; Narisawa, S.; Nakai, T. OS 1993, 71, 14.
13. Narasaka, K.; Iwasawa, N.; Inoue, M.; Yamada, T.; Nakashima, M.; Sugimori, J. JACS 1989, 111, 5340.
14. Oppolzer, W.; Chapuis, C. TL 1983, 24, 4665.
15. Terada, M.; Mikami, K.; Nakai, T. TL 1991, 32, 935.
16. Hayashi, Y.; Narasaka, K. CL 1990, 1295.
17. Hayashi, Y.; Niihata, S.; Narasaka, K. CL 1990, 2091.
18. Hayashi, Y.; Narasaka, K. CL 1989, 793.
19. Narasaka, K.; Hayashi, Y.; Shimada, S. CL 1988, 1609.
20. Mikami, K.; Matsukawa, S. JACS 1993, 115, 7039.
21. Barr, D. A.; Grigg, R.; Sridharan, V. TL 1989, 30, 4727.

Nicos A. Petasis

University of Southern California, Los Angeles, CA, USA

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