[58602-50-9] · AlH2I · Lithium Aluminum Hydride-Copper(I) Iodide · (MW 155.90)
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
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
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
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
For a discussion on alternative methods of 1,4-reduction of enones, see Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride.
Ronald K. Russell
The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ, USA