Carbonyl compounds unsaturated, reduction

The disadvantages associated with the Clemmensen reduction of carbonyl compounds (see 3 above), viz., (a) the production of small amounts of carbinols and unsaturated compounds as by-products, (h) the poor results obtained with many compounds of high molecular weight, (c) the non-appUcability to furan and pyrrole compounds (owing to their sensitivity to acids), and (d) the sensitivity to steric hindrance, are absent in the modified Wolff-Kishner reduction. 

Addition of dihydrosilane to a, /J-unsaturated carbonyl compounds such as citral (49), followed by hydrolysis, affords saturated citroneJlal (50) directly. The reaction is used for the selective reduction of conjugated double bonds[45,46]. In addition to Pd catalyst, the use of a catalytic amount of... 

Triethylammonium formate is another reducing agent for q, /3-unsaturated carbonyl compounds. Pd on carbon is better catalyst than Pd-phosphine complex, and citral (49) is reduced to citronellal (50) smoothly[55]. However, the trisubstituted butenolide 60 is reduced to the saturated lactone with potassium formate using Pd(OAc)2. Triethylammonium formate is not effective. Enones are also reduced with potassium formate[56]. Sodium hypophosphite (61) is used for the reduction of double bonds catalyzed by Pd on charcoal[57]. 

A particularly useful reaction has been the selective 1,2-reduction of a, P-unsaturated carbonyl compounds to aHyUc alcohols, accompHshed by NaBH ia the presence of lanthanide haUdes, especially cerium chloride. Initially appHed to ketones (33), it has been broadened to aldehydes (34) and acid chlorides (35). NaBH by itself gives mixtures of the saturated and unsaturated alcohols. 

Reduction of unsaturated carbonyl compounds to the saturated carbonyl is achieved readily and in high yield. Over palladium the reduction will come to a near halt except under vigorous conditions (73). If an aryl carbonyl compound, or a vinylogous aryl carbonyl, such as in cinnamaldehyde is employed, some reduction of the carbonyl may occur as well. Carbonyl reduction can be diminished or stopped completely by addition of small amounts of potassium acetate (i5) to palladium catalysts. Other effective inhibitors are ferrous salts, such asferroussulfate, at a level of about one atom of iron per atom of palladium. The ferrous salt can be simply added to the hydrogenation solution (94). Homogeneous catalysts are not very effective in hydrogenation of unsaturated aldehydes because of the tendencies of these catalysts to promote decarbonylation. 

After reduction of the nitro function of the porphyrin, the porphyrinamine intermediate can be reacted with z./l-unsaturated carbonyl compounds to yield porphyrins with a fused pyridine ring, which is formed by Michael addition, imine formation and dehydrogenation. 

D. Caine, Reduction and related reaction of a, ji-unsaturated carbonyl compounds with metals in liquid ammonia. Organic Reaktions, Vol. XXIII, 1 (1976). 

For a review of reductions of a,p-unsaturated carbonyl compounds with metals in liquid NH3, see Caine, D. Org. React., 1976, 23, 1. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

When the conditions are controlled properly, Zn can mediate the reduction of the C-C double bond of a, (3-unsaturated carbonyl compounds in the presence of a nickel catalyst in aqueous ammonium chloride (Eq. 10.7). The use of ultrasonication enhances the rate of the reaction.15 Sodium hydrogen telluride, (NaTeH), prepared in situ from the reaction of... 

Steric factors are also important in hydrodimerizations carried out in acidic media. Excessive steric hindrance about the 0-carbon in an a, 0-unsaturated carbonyl compound can retard tail-to-tail coupling, e.g., 2 130 - 131, and lead to products of head-to-head (and occasionally head-to-tail) coupling. Thus in the reduction of mesityl oxide at pH lg.4 there is also formed a small amount of ketone 140, apparently formed via head-to-head coupling of 130 and subsequent pinacol rearrangement of 139 134) ... 

From the very successful developments of the alcohol dehydrogenase technology for production of secondary alcohols and enzymatic reductive amination of keto-acids for production of amino acids, it is expected that we will also soon see applications for other enzymatic redox chemistries for example, reduction of unsaturated carbonyl compounds with... 

The stereoselective 1,4-addition of lithium diorganocuprates (R2CuLi) to unsaturated carbonyl acceptors is a valuable synthetic tool for creating a new C—C bond.181 As early as in 1972, House and Umen noted that the reactivity of diorganocuprates directly correlates with the reduction potentials of a series of a,/ -unsaturated carbonyl compounds.182 Moreover, the ESR detection of 9-fluorenone anion radical in the reaction with Me2CuLi, coupled with the observation of pinacols as byproducts in equation (40) provides the experimental evidence for an electron-transfer mechanism of the reaction between carbonyl acceptors and organocuprates.183... 

For a example of nickel-catalyze conjugate reduction of a,(3 unsaturated carbonyl compounds affording enol derivatives, seerBourhis, R. Frainnet, E. Moulines, F. J. Organomet. Chem. 1977, 141, 157-171. 

With an operating catalytic cycle for the reductive opening of epoxides at hand, we decided to investigate the preparatively more important formation of carbon—carbon bonds. Inter-molecular addition reactions to a,(3-unsaturated carbonyl compounds have been described for the stoichiometric process of Nugent and RajanBabu [5], The general concept behind the catalytic conditions is outlined in Scheme 12.16. 

The key features of the catalytic cycle are trapping of the radical generated after cycliza-tion by an a,P-unsaturated carbonyl compound, reduction of the enol radical to give an enolate, and subsequent protonation of the titanocene alkoxide and enolate. The diaster-eoselectivity observed is essentially the same as that achieved in the simple cyclization reaction. An important point is that the tandem reactions can be carried out with alkynes as radical acceptors. The trapping of the formed vinyl radical with unsaturated carbonyl compounds occurs with very high stereoselectivity, as shown in Scheme 12.21. 

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