Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride1,2

NaCuHBr.AlH(OCH2CH2OMe)2
(CuBr)

[7787-70-4]  · BrCu  · Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride  · (MW 143.45) (NaAlH2(OCH2CH2OMe)2)

[22722-98-1]  · C6H16AlNaO4  · Copper(I) Bromide-Sodium Bis(2-methoxyethoxy)aluminum Hydride  · (MW 202.19)

(in situ prepared hydridocopper reagent; 1,4-reduction of a,b-unsaturated ketones,2 esters,2 lactones,3 nitriles4 and selected alkynes5)

Preparative Method: 2 a benzene (toluene) solution of Sodium Bis(2-methoxyethoxy)aluminum Hydride (16 mmol of hydride) is added dropwise to a suspension of dry6 Copper(I) Bromide (8 mmol) in anhydrous THF at 0 °C under an inert atmosphere. After 30 min, the black mixture is cooled to -78 °C and anhydrous 2-butanol (18 mmol) is added, followed by a THF solution of substrate (1 mmol). The mixture is stirred at -20 °C for 2 h, quenched with water and poured into saturated aqueous ammonium chloride solution. After ether addition, the organic layer is washed with water and aqueous ammonium chloride solution and dried.

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

Modifications.

Copper(I) Iodide has been used as the copper source for the reduction of a,b-unsaturated esters7 and butenolides.8

a,b-Unsaturated Ketones.

The reagent is used for the 1,4-reduction of a,b-unsaturated ketones (eq 1).2,9-12 This reagent is reported to reduce acyclic enones and enoates (in the presence of 2-butanol) better than the Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride reagent.9 The reagent has been used to reduce 2-cyclopentenone,13 cyclohexenones,9,14,15 and macrocyclic enones.16

Other Enones.

The reagent reduces a,b-unsaturated esters (eq 2),9,17-22 lactones (eqs 3 and 4),3,23-25 and nitriles (eq 5).4

Alkynes.

The reduction of alkynic esters affords unsaturated esters, albeit in poor yield and as a cis/trans mixture (eq 6).9 In contrast to this, the reduction of 1-alkyl-3-(trifluoromethyl)propargyl alcohols affords only the cis alkene (eq 7).5 Deuterium trapping experiments (AcOD) resulted in deuterium incorporation at the CF3 sp2 carbon.

Limitations.

Although the exact structure of this reagent has not been determined, it is clearly different from other hydridocopper reagents.9 The title reagent fails to reduce sterically hindered enones (e.g. 1 and 2).26-29 This reagent also lacks chemoselectivity, such that it will reduce saturated ketones to alcohols and alkyl (aryl) bromides to their corresponding hydrocarbons.30 The reagent [(Ph3P)CuH]6 is reported to reduce a,b-unsaturated carbonyl compounds in the presence of alkyl halides or sulfonates.31

Alternative Methods.

The 1,4-reduction of enones can be accomplished by many other methods, such as catalytic hydrogenation,32,33 dissolving metal reduction,34,35 benzylamine/potassium t-butoxide,36 Pentacarbonyliron/base,37,38 lithium or potassium trialkyl(aryl)borohydrides,39,40 NaHFe2(CO)8,41 Tri-n-butylstannane,42 Diphenylsilane-Tetrakis(triphenylphosphine)palladium(0)-Zinc Chloride,30,43 Selenium/CO/H2O,44 and Sodium Borohydride/CuCl.45 See Copper(I) Bromide-Lithium Trimethoxyaluminum Hydride, Lithium Aluminum Hydride-Copper(I) Iodide, Lithium n-Butyl(hydrido)cuprate. For a discussion on alternative methods of alkyne reduction to cis-alkenes, see Magnesium Hydride-Copper(I) Iodide.


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Ronald K. Russell

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



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