(R,R)-[Ethylene-1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)]titanium (R)-1,1-Bi-2,2-naphtholate


[143063-72-3]  · C40H36O2Ti  · (R,R)-[Ethylene-1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)]titanium (R)-1,1-Bi-2,2-naphtholate  · (MW 596.64) (S,S,S)


(precursor to a catalyst for the asymmetric reduction of unsaturated organic molecules1)

Physical Data: mp 274.5-277 °C (dec); [a]578, -3700° (c = 0.45 mg cm-3 in CHCl3).

Solubility: sol THF, benzene, toluene; slightly sol ether; very slightly sol hexane.

Preparative Methods: originally prepared and characterized by Brintzinger et al. from the corresponding dichloride derivative and (R)-1,1-Bi-2,2-naphthol.2 The dichloride is synthesized by reacting the dilithium salt of 1,2-bis(3-indenyl)ethane with Titanium(IV) Chloride followed by hydrogenation over Platinum(IV) Oxide.2 Since the original report, two improved procedures for its preparation have appeared.3,1b

Handling, Storage, and Precautions: the complex is air and moisture stable and can be stored indefinitely.

Catalyst Generation and Handling.

When complex (1) is allowed to react with 2 equiv of n-Butyllithium and 2.5-3 equiv of phenylsilane in THF under an inert atmosphere, an active reduction catalyst, complex (2), is formed (eq 1).

Complex (2) is believed to be a titanium(III) hydride and has not been isolated or characterized (no 1H NMR signals for any titanium species are observable, probably as a result of the paramagnetic nature of the complex). This complex is extremely air sensitive and must be handled under rigorously oxygen-free conditions. Solutions of complex (2) are stable under inert atmosphere for at least 24 h and exhibit no sensitivity to light. For synthetic purposes it is most convenient to generate the active catalyst from complex (1) immediately prior to use.

Reduction of Unfunctionalized Alkenes.

The asymmetric reduction of trisubstituted alkenes with this system has recently been investigated.4 It was shown that high ee's could be achieved in this reaction, although high pressures and long reaction times were necessary. As an example, trans-methylstilbene can be reduced at 2000 psi of hydrogen and 65 °C with excellent chemical and optical yield (eq 2). This represents the first catalyst system for the reduction of unfunctionalized, trisubstituted alkenes with good to excellent enantioselectivity.

Reduction of Imines.

This catalyst system is very effective for the asymmetric hydrogenation of imines.1b For example, N-(1-cyclohexyl)ethylidenebenzylamine (as a mixture of anti and syn isomers) can be reduced in excellent yield and good enantiomeric excess (eq 3). The reaction must be conducted at high pressures in order to achieve maximum enantioselectivity. This effect was found for several acyclic imines.

The reduction of cyclic imines with this system was found to proceed under much milder conditions.5 For example, 2-phenylpyrroline was reduced at 80 psi of hydrogen to afford 2-phenylpyrrolidine in good yield and excellent enantiomeric excess (eq 4).

This reaction was found to be applicable to ring sizes of 5 to 7 (although more forcing conditions were required for six-membered rings) and was compatible with several functional groups. In all cases studied, ee's greater than 95% were observed. Among the functional groups investigated were acetals, silyl ethers, trisubstituted alkenes, and alcohols. Monosubstituted alkenes were completely reduced and disubstituted alkenes were partially reduced and isomerized under the standard conditions. The reaction has the practical advantage that the active catalyst can be generated in a Fisher-Porter bottle and the reaction can then be conducted in the same vessel. Thus no transfer of air-sensitive materials is necessary.

Related Reagents.

(-)-[Ethylene-1,2-bis(h5-4,5,6,7-tetrahydro-1-indenyl)]zirconium (R)-1,1-Bi-2,2-naphtholate; (±)-1,1-Ethylenebis(4,5,6,7-tetrahydro-1-indenyl)zirconium Dichloride.

1. (a) Buchwald, S. L.; Kreutzer, K. A.; Willoughby, C. A.; Grossman, R. B.; Berk, S. C.; Spaltenstein, E.; Gutierrez, A. PCT Int. Appl. 92 09 545. (b) Willoughby, C. A.; Buchwald, S. L. JACS 1992, 114, 7562.
2. Wild, F. R. W. P.; Zsolnai, L.; Huttner, G.; Brintzinger, H. H. JOM 1982, 232, 233.
3. (a) Collins, S.; Kuntz, B. A.; Taylor, N. J.; Ward, D. G. JOM 1988, 342, 21. (b) Collins, S.; Kuntz, B. A.; Hong, Y. JOC 1989, 54, 4154.
4. Broene, R. D.; Buchwald, S. L. JACS 1993, 115, 12569.
5. Willoughby, C. A.; Buchwald, S. L. JOC 1993, 58, 7627.

Christopher A. Willoughby

Massachusetts Institute of Technology, Cambridge, MA, USA

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