Reduction of conjugated double bonds

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... 

Since sodium borohydride usually does not reduce the nitrile function it may be used for selective reductions of conjugated double bonds in oc,/l-un-saturated nitriles in fair to good yields [7069,1070]. In addition some special reagents were found effective for reducing carbon-carbon double bonds preferentially copper hydride prepared from cuprous bromide and sodium bis(2-methoxyethoxy)aluminum hydride [7766], magnesium in methanol [7767], zinc and zinc chloride in ethanol or isopropyl alcohol [7765], and triethylam-monium formate in dimethyl formamide [317]. Lithium aluminum hydride reduced 1-cyanocyclohexene at —15° to cyclohexanecarboxaldehyde and under normal conditions to aminomethylcyclohexane, both in 60% yields [777]. 

Another approach to preparing enantiomerically pure carboxylic acids and related compounds is via enanhoselective reduction of conjugated double bonds using NAD(P)H-dependent enoate reductases (EREDs EC 1.3.1.X), members of the so-called Old Yellow Enzyme family [44]. EREDs are ubiquitous in nature and their catalytic mechanism is well documented [45]. They contain a catalytic flavin cofactor and a stoichiometric nicotinamide cofactor which must be regenerated (Scheme 6.23). 

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. ... 

Various diphenylethylenes are reduced in high yield by magnesium in methanol. Expectedly, reductions of conjugated double bonds via one-electron transfer processes can also be carried out electro-chemically. Scheme 87 illustrates both the reduction of a conjugated alkene and partial trapping of the intermediate anion radical to yield a mixed hydrodimerization product. 

Isomerization of allylic sulfones and reduction of conjugated double bonds (Eq. 62), are possible disadvantages of the use of Mg as an electron-transfer agent.117 The occurrence of Julia olefination of 1,2-disulfone derivatives is another important drawback when performing reductive desulfonylation on these kinds of substrates (Eq. 63).118... 

Cleavage of allylic C-O bonds (Eq. 80),135 reduction of conjugated double bonds,136 137 and reductive dehalogenations138 139 occasionally intervene when reducing functionalized sulfones with Na/Hg. These side reactions are dependent on the substrates and reaction conditions, and should not be considered as general limitations. 

Reduction of conjugated double bonds. This selective reduction method is valuable in situations in which other double bonds must be retained. Such a reaction, further facilitated with ultrasound, has been employed during a synthesis of penitrem-D. 

Reduction of conjugated double bonds in a,p-unsaturated aldehydes and ketones proceeds with high selectivity by the use of sodium dithionite under PTC conditions ... 

This type of reaction may be divided into two categories (1) reduction of isolated double bonds and (2) reduction of conjugated double bonds. There are very few examples of the former in the steroid field, all involving the use of unidentified fecal anaerobes to reduce A -compounds to the 5j3-series (C-133, S-914), and there is no adequate basis for the presentation of arguments about mechanism. 

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. 

Azo dye molecules have color due to their azo bond, auxochromes, and system of conjugated double bonds. The azo bond, while resistant to aerobic degradation, can be cleaved under anaerobic or anoxic condition, resulting in decolorization and the production of aromatic amines. Anaerobic reduction of the azo dyes is relatively easy to achieve, but the products have been found to be biorecalcitrant... 

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. 

In systems of conjugated double bonds catalytic hydrogenation usually gives a mixture of all possible products. Conjugated dienes and polyenes can be reduced by metals sodium, potassium, or lithium. The reduction is accomplished by 1,4-addition which results in the formation of a product with only one double bond and products of coupling and polymerization. Isoprene was reduced in 60% yield to 2-methyl-2-butene by sodium in liquid ammonia [357]. Reduction of cyclooctatetraene with sodium in liquid ammonia gave a... 

Double bonds conjugated with benzene rings are reduced electrolytically [344] (p. 23). Where applicable, stereochemistry can be influenced by using either catalytic hydrogenation or dissolving metal reduction [401] (p. 24). Indene was converted to indane by sodium in liquid ammonia in 85% yield [402] and acenaphthylene to acenaphthene in 85% yield by reduction with lithium aluminum hydride in carbitol at 100° [403], Since the benzene ring is not inert toward alkali metals, nuclear reduction may accompany reduction of the double bond. Styrene treated with lithium in methylamine afforded 25% of 1-ethylcyclohexene and 18% of ethylcyclohexane [404]. 

The major pathway for the degradation of testosterone in humans occurs in the liver, with the reduction of the double bond and ketone in the A ring, as is seen in other steroids with a A4-ketone configuration in the A ring. This leads to the production of inactive substances such as androsterone and etiocholanolone that are then conjugated and excreted in the urine. 

Most researchers have found 1,2-addition of hydrogen in C=C hydrogenation of conjugated double bonds for example, in the reduction of 1-vinylcyclohexene, 4-methylene-l,2,3-trimethylcyclobutene-3-ol benzoate and some steroid derivatives. 

The reduction of the double bonds conjugated to electron-withdrawing groups is examined later (Section 3.2.9). 

The idea was that the lactone 227 could come from 228 by the sequence (i) stereo- and regioselective a-hydroxylation 229, (ii) Wittig style reaction on the ketone to add the extra two carbon atoms 230, (iii) stereoselective conjugate reduction of the double bond with the OH group directing the reagent to the bottom face of the alkene, and (iv) lactonisation. 

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