Copper(I) Iodide-Lithium Trimethoxyaluminum Hydride1


[7681-65-4]  · CuI  · Copper(I) Iodide-Lithium Trimethoxyaluminum Hydride  · (MW 190.45)

[12076-93-6]  · C3H10AlLiO3  · Copper(I) Iodide-Lithium Trimethoxyaluminum Hydride  · (MW 128.05)

(in situ prepared hydridocopper reagent; reductive removal of halogen or mesyloxy groups; reduction of epoxides to alcohols2)

Preparative Method: 2 an anhydrous THF solution of lithium trimethoxyaluminum hydride (2.0 mmol) is added dropwise to an ice-cold suspension of Copper(I) Iodide (dried at 100 °C in vacuo prior to use; 1 mmol) in THF under an inert atmosphere. After 30 min, the resulting brown mixture is treated with substrate (1 mmol). The cooling bath is removed after 15 min and the mixture is stirred vigorously for 2 h at room temperature. Additional THF may be added to effect efficient stirring. The reaction mixture is quenched with methanol, diluted with ether, and filtered through Celite. This filtrate is washed with saturated aqueous ammonium chloride and dried.

Handling, Storage, and Precautions: use in a fume hood.

General Discussion.

This reagent was first reported for the reductive removal of primary, secondary, tertiary, allyl, vinyl, aryl, and neopentyl bromides. In all cases the halide was removed in excellent yield (85-100%) (Table 1). Simple primary and secondary mesylates and cyclohexene oxide were reductively cleaved by the conditions stated. However, the use of additional reagent and a longer reaction time (15 h) was required for the reduction of 1-chlorooctane to n-octane (96% yield).2 This reagent was used to prepare allocyathin B3 methyl acetal from a vinyl bromide (eq 1)4 and (+)-cyclohex-2-en-1-ol from its corresponding vinyl iodide (1).5 The reduction of either exo- or endo-2-bromonorbornane with CuD (prepared from LiAlD(OMe)3 and CuI) proceeds with 100% retention, whereas the corresponding mesylates are reduced with complete inversion of stereochemistry.2 This retention of stereochemistry is also observed for an adamantane ring system.6


There are examples where mesylate reductions have produced only recovered starting material (e.g. 2 and 3),7,8 a mixture of reduced product and the corresponding alkene,9 or alcohols from O-S cleavage (e.g. 4).10

Alternative Methods.

Potassium Tri-s-butylborohydride has been used as the hydride source.3 The reductive removal of halogen, hydroxy, or mesyloxy groups can be accomplished by a number of different methods, such as hydrogenolysis,11 TiCl3.3THF-Mg,12 Bu3SnH-thiocarbonate,13,14 NaI-Zn,15 trialkylSiH-AlCl3,16 LiAlH4-transition metal,17-19 LiEt3BH,20,21 NaBH4,22 NaBH4-Ni023 and i-PrMgBr-titanocene dichloride.24 See also Lithium n-Butyl(hydrido)cuprate and Lithium Tri-t-butoxyaluminum Hydride. Other hydridocopper reagents include Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride and Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride.

1. Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J. A. T 1984, 40, 5005.
2. Masamune, S.; Rossy, P. A.; Bates, G. S. JACS 1973, 95, 6452.
3. Yoshida, T.; Negishi, E. CC 1974, 762.
4. Ayer, W. A.; Browne, L. M.; Mercer, J. R.; Taylor, D. R.; Ward, D. E. CJC 1978, 56, 717.
5. Mori, K.; Tamada, S.; Uchida, M.; Mizumachi, N.; Tachibana, Y.; Matsui, M. T 1978, 34, 1901.
6. Chang, T. C.; Gadberry, J. F.; Lightner, D. A. SC 1984, 14, 1321.
7. Eyley, S. C.; Williams, D. H. JCS(P1) 1976, 731.
8. Mervic, M.; Ghera, E. JACS 1977, 99, 7673.
9. Baldwin, S. W.; Tomesch, J. C. JOC 1980, 45, 1455.
10. Baldwin, J. E.; Bonacorsi, S., Jr.; Carlson, R. G.; Graber, F. D. JOC 1993, 58, 981.
11. Pinder, A. R. S 1980, 425.
12. Tyrlik, S.; Wolochowicz, I. CC 1975, 781.
13. Barton, D. H. R.; McCombie, S. W. JCS(P1) 1975, 1574.
14. Hartwig, W. T 1983, 39, 2609.
15. Fujimoto, Y.; Tatsuno, T. TL 1976, 3325.
16. Doyle, M. P.; McOsker, C. C.; West, C. T. JOC 1976, 41, 1393.
17. Shimizu, N.; Watanabe, K.; Tsuno, Y. CL 1983, 1877.
18. Ashby, E. C.; Lin, J. J. JOC 1978, 43, 1263.
19. Obafemi, C. A.; Lee, C. C. CJC 1990, 68, 1998.
20. Holder, R. W.; Matturro, M. G. JOC 1977, 42, 2166.
21. Krishnamurthy, S.; Brown, H. C. JOC 1983, 48, 3085.
22. Hutchins, R. O.; Kandasamy, D.; Dux, F., III; Maryanoff, C. A.; Rotstein, D.; Goldsmith, B.; Burgoyne, W.; Cistone, F.; Dalessandro, J.; Puglis, J. JOC 1978, 43, 2259.
23. Lin, S. T.; Roth, J. A. JOC 1979, 44, 309.
24. Rilatt, J. A.; Kitching, W. OM 1982, 1, 1089.

Ronald K. Russell

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

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