[16903-61-0] · C36H34BCuP2 · Bis(triphenylphosphine)copper(I) Borohydride · (MW 602.97)
Alternate Name: (tetrahydroborato)bis(triphenylphosphine)copper.
Physical Data: mp 172-174 °C (dec) (from CHCl3/ether);2 177 °C (dec) (from CHCl3/ethanol);3 recrystallizing from benzene/ethanol gives a stable 1:1 complex with benzene, mp 187 °C (dec),3 as white needles.
Solubility: sol THF, CHCl3, CH2Cl2, benzene; slightly sol acetone; insol ether, ethanol, and water.
Form Supplied in: commercially available as a white solid, or is easily prepared.
Preparative Method: by adding Copper(I) Chloride to a stirring solution of 2 equiv of Triphenylphosphine in chloroform. Once the copper chloride is dissolved the mixture is treated with a suspension of Sodium Borohydride (1 equiv) in ethanol for at least 15 min to ensure complete reaction. The solution is washed with water and dried over anhydrous magnesium sulfate. Diethyl ether is added to precipitate the reagent as fine white needles (90% yield).2
Purification: can be recrystallized from CHCl3/ether or CHCl3/ethanol mixtures.
Handling, Storage, and Precautions: stable to air and water. It should be handled in a well-ventilated hood; contact with the eyes and skin should be avoided.
Bis(triphenylphosphine)copper(I) borohydride selectively reduces many acid chlorides to aldehydes (eq 1) in good yields (Table 1).2,4a Acetone is the best solvent for these reductions, and addition of 2 equiv of triphenylphosphine to the reaction mixture increases yields. It is thought that 1 equiv binds to the bis(triphenylphosphine)copper(I) chloride byproduct and the second equiv traps the BH3 given off in the reaction.4a Formation of an acylphosphonium salt as an intermediate in the reduction has also been postulated.4c
The reduction of aldehydes and ketones to the corresponding alkanes can be achieved via the p-toluenesulfonylhydrazone derivative using the title reagent.5 Tosylhydrazones of ketones (eq 2) are reduced consistently in good yield and tosylhydrazones of aldehydes are reduced in slightly lower yields (Table 2).5a The p-toluenesulfonylhydrazones derived from aromatic and a,b-unsaturated aldehydes and ketones cannot be reduced by this method. Sterically hindered hydrazones such as camphor tosylhydrazone are also reduced only with difficulty and in low yields.
A typical procedure involves mixing an equimolar ratio of the hydrazone and bis(triphenylphosphine)copper(I) borohydride in refluxing chloroform; benzene, toluene, and acetone may also be used. The reaction is usually complete in 2 h. Excess triphenylphosphine does not improve yields, as is the case for the reduction of acid chlorides to aldehydes. The reductions of 2,4,6-triisopropylbenzene (trisyl) hydrazones proceed in only moderate yields at rt. Increased temperature reduces the yields of trisylhydrazone reductions.
The reduction of a tosylhydrazone using this reagent has been performed in the synthesis of naturally occurring 12-tridecanolide (eq 3).5b The reduction of an aldehyde to the corresponding alkane via the tosylhydrazone, in the presence of other reducible and sensitive functional groups, has been demonstrated in the conversion of the 16-membered macrolide antibiotic tylosin to 20-dihydro-20-deoxytylosin (eq 4).5c
Strong acid-catalyzed reduction of aldehydes and ketones with the title reagent can be carried out with high chemo- and stereoselectivity.6 While aldehydes were not reduced at room temperature in acetone under neutral conditions by using bis(triphenylphosphine)copper(I) borohydride, aromatic aldehydes such as 4-nitrobenzaldehyde containing strong electron-withdrawing groups were reduced quantitatively in chloroform or dichloromethane in the absence of a catalyst. In the presence of a strong acid catalyst, however, aldehydes and ketones are generally reduced (eq 5) in high yield to the corresponding alcohol (Table 3).6
Typical conditions necessary to effect the reduction of aldehydes and ketones is to bubble gaseous hydrogen chloride through a dichloromethane solution of the carbonyl compound and 1 equiv of bis(triphenylphosphine)copper(I) borohydride at room temperature for 10 min. Sterically hindered ketones are not reduced under these conditions. A strong Lewis acid such as Aluminum Chloride, however, will catalyze the high yield reduction of hindered ketones such as camphor and 3,3,5-trimethylcyclohexanone. The steric size of the reductant contributes to its good stereoselectivity in the reduction of ketones. a,b-Unsaturated aldehydes are easily reduced under these conditions to the primary allylic alcohol, but a,b-unsaturated ketones give complex mixtures of products.
Bis(triphenylphosphine)copper(I) borohydride can be used as an alternative reagent to 1,3-Propanedithiol for the selective reduction of aromatic azides to aromatic amines.7 One equiv of the reducing agent in chloroform at rt reduces aromatic azides in good yields (eq 6). Aromatic rings substituted with electron-withdrawing groups are reduced in 30 min, while aromatic rings substituted with electron-donating groups are reduced more slowly (Table 4).7 The rates of these reductions increase in refluxing chloroform or in the presence of an acid catalyst. Aliphatic azides are not affected under the conditions necessary to reduce the more activated aromatic azides.
Lithium Tri-t-butoxyaluminum Hydride;
David A. Barda
Indiana University, Bloomington, IN, USA