Double bonds, keto conjugated reduction

Unsaturated epoxides are reduced preferentially at the double bonds by catalytic hydrogenation. The rate of hydrogenolysis of the epoxides is much lower than that of the addition of hydrogen across the carbon-carbon double bond. In a, -unsaturated epoxides borane attacks the conjugated double bond at -carbon in a cis direction with respect to the epoxide ring and gives allylic alcohols [660], Similar complex reduction of epoxides occurs in a-keto epoxides (p. 126). 

In an interesting reaction, -santonin was reduced with lithium in liquid ammonia so that the lactone was hydrogenolyzed to an add and one of the double bonds conjugated with the carbonyl was reduced. The other double bond as well as the keto group did not undergo reduction [1091]. 

Reduction of conjugated double bonds. This reagent reduces double bonds conjugated with a keto or carboxyl group in good to excellent yield. It also reduces aryl imines to the corresponding secondary amines. ... 

Treatment of particular fully conjugated heterocyclic enaminediones with NaBH4 resulted in a chemoselective reduction of the keto carbonyl group, followed by a stereoselective reduction of the carbon-carbon double bond (Scheme 100). Catalytic hydrogenation allowed a complete reduction of the second carbonyl group. 

Modification of Ring a.—Some of the modifications mentioned above (Scheme 11) are common to many organisms.The complete structure of A -3-keto-steroid isomerase (EC 5.3.3.1) has been determined. It has three sub-units, each of 125 amino-acids. This enzyme transfers the 4/9-hydrogen atom to the 6j3-position as the A -double bond is moved into conjugation. Starfish convert cholesterol into 5a-cholest-7-enol by a similar process. The A -double bond is introduced only after reduction of the A -3-one. ... 

The reduction of double bonds conjugated with keto groups may be viewed as part of the illustrated equilibrium process, the reverse of which is the dehydrogenation of ketosteroids. The nature of the reagent X, be it protein-bound flavin, quinone. 

Sites of Reaction. Reduction of conjugated double bonds was first observed by Mamoli and Schramm (M-548) with a crude culture of putrefactive bacteria. The pure culture, described as Bacillus putrificus, reduced 3-keto-A -androstenes to 3-keto-5 -androstanes and Sa-hydroxy-S S-androstanes (M-545). This culture is no longer available (E-202), but a modern equivalent is Clostridium paraputrificum, described by Schubert (Ap-71, S-823). The properties of the latter are described in greater detail in the section on reduction of carbonyl groups. 

Addition of deuterium to ergosterol acetate was shown to form the 5a,6a-dideuterio reduction product under mild conditions (Equation 15.4). This result illustrates a number of features of the reactivity of Wilkinson s catalyst. First, the conjugated diene is reduced in preference to the C21-C22 double bond. Second, the diene is reduced from the less-crowded a-face of the steroid. Neither the remaining trisubstituted double bond nor the trans disubstituted A double bond are affected. Finally, no isotopic exchange takes place during this reaction. This selectivity has been used to specifically label prostaglandins with tritium (Equation 15.5). The sensitive 3-keto alcohol is unperturbed. 

These examples illustrate the interest of the method, very short times, high yields, and excellent selectivity, since non-conjugated olefins or keto groups remain intact. Unactivated zinc can be used. Instead of temperatures of ca. 180 C, much milder conditions can be used (r.t. to 50 C). The reductions can be run in a bath for quantities less than 1 g larger amounts require the use of a pulsed probe emitter.Olefins activated by acid, ester, dienone, and quinone groups are reduced quantitatively in a few hours, and in many instances, in only minutes. Non-conjugated double bonds remain intact. Examples of this chemoselectivity applied to ene-diones are shown in Fig. 15. 

Conjugate Addition Reactions. BSA was found to activate 1,4-conjugate addition of bis[(trimethylstannyl)vinyl)] cuprate reagent 27 to a, 8-unsaturated keto-esters without concomitant reduction of the double bond. With the keto ester 26, a near-quantitative yield (92%) of the starmylvinyl adduct 28 was obtained with no trace of the reduction product 29 (eq 37). ... 

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