Copper hydride unsaturated carbonyl compounds

Conjugate reduction.1 This stable copper(I) hydride cluster can effect conjugate hydride addition to a,p-unsaturated carbonyl compounds, with apparent utilization of all six hydride equivalents per cluster. No 1,2-reduction of carbonyl groups or reduction of isolated double bonds is observed. Undesirable side reactions such as aldol condensation can be suppressed by addition of water. Reactions in the presence of chlorotrimethylsilane result in silyl enol ethers. The reduction is stereoselective, resulting in hydride delivery to the less-hindered face of the substrate. 

There are many examples of the stereoselective addition of nucleophiles to carbonyl groups in which chelation to the titanium center should be critical—reported examples include the stereoselective hydride reduction of a- or /3-hydroxyketones (Eq. 305) [684-686], of a-phosphino ketones [687], of a-sulfonylketones [688], and of an a,/3-unsaturated carbonyl compound in a 1,4-fashion [689]. The stereoselective addition of organometallic compounds such as Grignard [669,690], zinc [691,692], copper [693], and other reagents [11] to carbonyl and related compoimds Ijy taking advantage of titanium chelation is a well established method in the stereoselective... 

The stable, well-characterized copper(I) hydride cluster [(PPh3)CuH]6 is a useful reagent for conjugate reduction of a,p-unsaturated carbonyl compounds. o This hydride donor is chemically compatible with chlorotrimethylsilane, allowing formation of silyl enol ethers via a reductive silation process (Scheme 53). 

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,P-unsaturated carbonyl compounds [42]. Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [PhaPCuH] enabled cych-zation of keto-enone 104 to provide the bicychc diastereomers 105 (66%) and 106 (16%). The reaction also was apphed to the transformation of 107... 

The formal conjugate addition of a hydride to a,f(-unsaturated carbonyl compounds with a subsequent aldol reaction of the in situ formed enolate has been frequently employed in organic synthesis. A broad range of procedures have been developed using various metals (e.g., rhodium, cobalt, iridium, mthenium, copper) and different reductants (typically silanes, boranes, or elemental hydrogen) [37]. 

Hubaut et has studied the liquid phase hydrogenation of polyunsaturated hydrocarbons and carbonyl compounds over mixed copper-chromium oxides. The selectivity of monohydrogenation was almost 100 % for conjugated dienes but much lower for a,p-unsaturated carbonyls. This was due to the adsorption competition between the unsaturated carbonyls and alcohols as primary products. It was suggested that the hydrogenation site was an octahed-rally coordinated Cu ion with two anionic vacancies, and an attached hydride ion. The Cr ion in the same environment was probably the active site for side reactions (hydrodehydroxylation, nucleophilic substitution, bimolecular elimination). 

Catalysts suitable specifically for reduction of carbon-oxygen bonds are based on oxides of copper, zinc and chromium Adkins catalysts). The so-called copper chromite (which is not necessarily a stoichiometric compound) is prepared by thermal decomposition of ammonium chromate and copper nitrate [50]. Its activity and stability is improved if barium nitrate is added before the thermal decomposition [57]. Similarly prepared zinc chromite is suitable for reductions of unsaturated acids and esters to unsaturated alcohols [52]. These catalysts are used specifically for reduction of carbonyl- and carboxyl-containing compounds to alcohols. Aldehydes and ketones are reduced at 150-200° and 100-150 atm, whereas esters and acids require temperatures up to 300° and pressures up to 350 atm. Because such conditions require special equipment and because all reductions achievable with copper chromite catalysts can be accomplished by hydrides and complex hydrides the use of Adkins catalyst in the laboratory is very limited. 

---