Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride1,2


[7787-70-4]  · BrCu  · Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride  · (MW 143.45) (LiAlH(OMe)3)

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

(in situ prepared hydridocopper reagent; reduces 1-alkynyl sulfides to cis-1-alkenyl sulfides;3 1,4-reduction of enones2,4)

Preparative Methods: 4 an anhydrous THF solution of lithium trimethoxyaluminum hydride (1.9 mmol) is added dropwise to a suspension of dry5 Copper(I) Bromide (1 mmol) in THF maintained at -5 to 0 °C under an inert atmosphere. After 30 min, the resulting dark brown suspension is cooled to -78 °C and treated with the substrate (1.1 mmol) via syringe. After a 50 min stirring time at -20 °C, methanol is added and the mixture is poured into a saturated aqueous ammonium chloride solution. The organic layer is removed from the blue (copper) layer and dried. A modification of this procedure has been reported where CuBr.Me2S was used as the copper source and HMPA was used as a cosolvent.6 In another procedure, CuBr.Me2S-lithium dimethoxyaluminum hydride-boron tribromide was used to prepare 2,6-dialkyl-2,3-dihydro-4-pyridones.7 Lithium Tri-t-butoxyaluminum Hydride-copper(I) bromide was used to regiospecifically reduce 1-acylpyridinium salts to the desired 1-acyl-1,4-dihydropyridines.8


The use of this reagent was first reported for the reduction of 1-alkynyl sulfides to cis-1-alkenyl sulfides (eq 1).3 Reduction of these compounds with Lithium Aluminum Hydride in THF produced the corresponding trans-1-alkenyl sulfides (eq 2). The reduction of 1-alkynyl phenyl sulfones also proceeds to give the cis-alkene.9 However, the reduction of alkynic esters showed a great tendency to oligomerize.4


This reagent reduces acyclic2,4,10 and bicyclic11,12 a,b-unsaturated ketones to ketones and 2-cyclohexenones to cyclohexanones.2,4 This reagent reduces cyclohexenones better than Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride.4 The deuterated copper reagent (copper(I) bromide-lithium trimethoxyaluminum deuteride) reacts with (1) to afford the deuterium label at the b-position (eq 3). The reduction of a,b-unsaturated esters tends to give high molecular weight materials.4


Although the exact structure of this reagent has not been determined, it is clearly different from other hydridocopper reagents4 and has been shown to be superior to the Lithium Aluminum Hydride-Copper(I) Iodide reagent13 for the preparation of (2) (eq 4).10 Substitution of Copper(I) Iodide for copper(I) bromide affords a much less selective reagent (Copper(I) Iodide-Lithium Trimethoxyaluminum Hydride).4 Additional limitations are discussed for the Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride reagent.

Alternative Methods.

For a discussion on alternative methods of alkyne reduction to cis-alkenes, see Magnesium Hydride-Copper(I) Iodide. For a discussion on alternative methods of 1,4-reduction of enones, see Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride. See also Copper(I) Iodide-Lithium Trimethoxyaluminum Hydride.

1. Lipshutz, B. H.; Wilhelm, R. S.; Kozlowski, J. A. T 1984, 40, 5005.
2. Semmelhack, M. F.; Stauffer, R. D. JOC 1975, 40, 3619.
3. Vermeer, P.; Meijer, J.; Eylander, C.; Brandsma, L. RTC 1976, 95, 25.
4. Semmelhack, M. F.; Stauffer, R. D.; Yamashita, A. JOC 1977, 42, 3180.
5. Kauffman, G. B.; Teter, L. A. Inorg. Synth. 1963, 7, 9.
6. Oehlschlager, A. C.; Singh, S. M.; Sharma, S. JOC 1991, 56, 3856.
7. Comins, D. L.; LaMunyon, D. H. TL 1989, 30, 5053.
8. Comins, D. L.; Abdullah, A. H. JOC 1984, 49, 3392.
9. Kleijn, H.; Vermeer, P. JOM 1986, 302, 1.
10. Kato, T.; Kondo, H. BCJ 1981, 54, 1573.
11. Rigby, J. H.; Sage, J.-M.; Raggon, J. JOC 1982, 47, 4815.
12. Schuda, P. F.; Ammon, H. L.; Heimann, M. R.; Bhattacharjee, S. JOC 1982, 47, 3434.
13. Ashby, E. C.; Lin, J. J. TL 1975, 4453.

Ronald K. Russell

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

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