Lithium Aluminum Hydride-Copper(I) Iodide

AlH2I

[58602-50-9]  · AlH2I  · Lithium Aluminum Hydride-Copper(I) Iodide  · (MW 155.90)

(in situ prepared hydridoaluminum reagent; 1,4-reduction of enones1,2)

Alternate Name: aluminum hydride iodide.

Physical Data: (.2THF): mp 165-166 °C.3

Preparative Methods: an anhydrous THF solution of Lithium Aluminum Hydride (1 mmol) is added dropwise to a suspension of dry Copper(I) Iodide (4 or 2 mmol)1 in THF maintained at 0 °C under an inert atmosphere. A deep black color is immediately produced with hydrogen gas evolution. After stirring for 3-20 min at 0 °C, the substrate (1 mmol) is added and stirring is continued for 15-60 min. The reaction is quenched with water and treated with a saturated aqueous ammonium chloride solution. Ether is added and the organic layer is dried.4

Modifications.

An important modification of the method utilizes HMPA as the co-solvent and a reaction temperature of -78 °C. In this case, the reactive agent is thought to be LiHCuI.2 Copper(I) iodide can be replaced with Copper(I) Bromide,5-7 Copper(I) t-Butoxide, or Mesitylcopper(I).8

The alane HAl[N(i-Pr)2]2 as well as the boron derivative HBI2 are effective at conjugate reduction of a,b-unsaturated ketones.9

Enones.

The reagent prepared in THF at 0 °C is AlH2I and not CuH or CuAlH4.1 This reagent reduces a- and b-substituted ketones in high yield (eqs 1-4). The cis analog of (1) is reduced to (2), albeit at a much slower rate. Cyclohexen-2-one is not reduced to cyclohexanone in THF at 0 °C;4 however, the enone is readily reduced at -78 °C when HMPA is added.2 This method is used to reduce trans-hex-2-enal to hexanal in 63% yield, along with 12% of the 1,2-reduced product.

The HMPA-THF method was used to reduce a,b-unsaturated ester (3),10 the unsaturated ketone (4),11 and the bicyclic enone (5) (eq 5).12 This method was used for other 1,4-reductions of enones.13-16 Interestingly, the cyclohexenone (6) was reduced by the LiAlH4-CuI-THF method. This reduction required 6 equiv of LiAlH4 and 24 equiv of CuI to produce ketone (7) in 40% yield (eq 6). The corresponding triene diols were also isolated.17

Limitation.

Treatment of enone (8) with LiAlH4-CuI-THF produced only the alcohol (9), whereas the Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride method produced the desired ketone (10) (eq 7).18

Alternative Methods.

For a discussion on alternative methods of 1,4-reduction of enones, see Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride.


1. Ashby, E. C.; Lin, J. J.; Kovar, R. JOC 1976, 41, 1939.
2. Tsuda, T.; Fujii, T.; Kawasaki, K.; Saegusa, T. CC 1980, 1013.
3. Schmidt, D. L.; Flagg, E. E. IC 1967, 6, 1262.
4. Ashby, E. C.; Lin, J. J. TL 1975, 4453.
5. Delbecq, F.; Baudouy, R.; Goré, J. JCR(S) 1980, 88.
6. Ishihara, T.; Kuroboshi, M. JFC 1987, 37, 113.
7. Ishihara, T.; Kuroboshi, M.; Yamaguchi, K.; Okada, Y. JOC 1990, 55, 3107.
8. Tsuda, T.; Yazawa, T.; Watanabe, K.; Fujii, T.; Saegusa, T. JOC 1981, 46, 192.
9. Ashby, E. C.; Lin, J. J. TL 1976, 3865.
10. Xia, X. B.; Munsey, M. S.; Du, H.; Wai, C. M.; Natale, N. R. H 1991, 32, 711.
11. Takano, S.; Inomata, K.; Ogasawara, K. CC 1990, 1544.
12. Takano, S.; Inomata, K.; Ogasawara, K. CC 1992, 169.
13. Goering, H. L.; Kantner, S. S. JOC 1981, 46, 4605.
14. Takano, S.; Sato, T.; Inomata, K.; Ogasawara, K. CC 1991, 462.
15. Honda, T.; Hoshi, M.; Tsubuki, M. H 1992, 34, 1515.
16. Aoki, K.; Nakajima, M.; Tomioka, K.; Koga, K. CPB 1993, 41, 994.
17. Muckensturm, B.; Pflieger, D. JCR(S) 1986, 376.
18. Kato, T.; Kondo, H. BCJ 1981, 54, 1573.

Ronald K. Russell

The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA



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