Reduction of unsaturated carbonyl compound

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. 

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... 

Two key chiral building blocks used in the total synthesis of a-tocopherol were prepared via microbial reduction of unsaturated carbonyl compounds with baker s yeast and with Geotrichum candidum Similarly, a key intermediate in the total synthesis of optically active natural carotenoids was prepared by microbial reduction of oxoisophorone with baker s yeast. An alternative approach to the synthesis of a-tocopherol employs a chiral building block that was obtained by baker s yeast reduction of 2-methyl-5-phenylpentadienal. ... 

The reduction of unsaturated carbonyl compounds by metal hydrides, and the reaction of organometallic nucleophiles with them, is a complicated story.87 It is more common than not, in each case, to get direct attack at the carbonyl group, but reaction in the conjugate position is well known. Conjugate reduction of a/i-unsaturated ketones by metal hydrides increases88 in the sequences Bu2iAlH < LiAlH4 < LiAlH(OMe)3 < LiAlH(OBu )3 and... 

Selective preparation of unsaturated alcohols from corresponding unsaturated carbonyl compounds is a difficult task to achieve with heterogeneous catalysis. Thermodynamically preferred reduction of double C=C bond can be restricted only with difficulties. Industrial relevance of unsaturated alcohols [1,2] in conjunction with economically expensive methods based on chemical reduction of unsaturated carbonyl compounds calls for the development of new catalysts for highly selective preparation of unsaturated alcohols. 

Posner et al. have applied Y-AI2O3 in the MPV reduction of unsaturated carbonyl compounds by /-PrOH [3]. Dehydrated alumina was able to deprotonate /-PrOH, by which means an aluminium isopropoxide catalyst was formed in situ. However, high temperatures were needed (up to 300°C) and only low yields of alcohol were obtained due to the occurrence of several side-reactions. 

Although the conjugated systems of polyenes and unsaturated carbonyl groups are similar in terms of structure and bonding, their chemical reactivities are significantly different. There is an overwhelmingly greater number of methods available for the partial reduction of unsaturated carbonyl compounds compared to the reduction of polyenes. The earliest procedures em-... 

Another fundamental reaction of >C=0 involves its reactivity as a base. In the Brpnsted sense, >C=0 - may react with a proton donor to produce a neutral ketyl radical (>C(.)OH, Figure 2, reaction 2). This is an important process when the reduction of a carbonyl compound is carried out under acidic conditions or in a protic media (e.g. elec-trochemically, with less reactive reducing reagents such as Mg or Zn, or when >C=0"-is produced via PIET and R3N"+ has available a-protons). The follow-up chemistry of >C(.)OH is that of a neutral free radical (dimerization to form pinacols, addition to unsaturated compounds, fragmentations/ring-openings, etc.), and thus beyond the scope of this chapter. 

Chapter 4 centers on two key transformations in organic synthesis (1) oxidation of alcohols and of unsaturated hydrocarbons (i.e., alkenes and alkynes) to carbonyl compounds (2) reduction of various carbonyl compounds to alcohols. 

The reader is already familiar with the reductions of carbonyl compounds to alcohols, since they were described in Sections 10.2-10.4. (To complete the overall picture in a,fi-unsaturated carbonyl compounds the C=C- instead of the C=0 double bond can also be reduced according to Figure 13.20, through the Birch and L-Selectride reduction of such carbonyl compounds.)... 

Even higher multiplicities of specificity combinations are possible. In Scheme 49, conversion of (115) to (116) involves regiospecific reduction of an enantiotopic carbonyl group concurrently with enantiotopic face specificity. This transformation can also be achieved using Saccharomyces species, with the level of (116) produced being enhanced by the addition of unsaturated carbonyl compounds, such as acrolein. ... 

The reductive cyclization of unsaturated carbonyl compounds can also be achieved by using chemical reducing reagents, such as Al-amalgam, MgTiCl4, and NaNH3, but in general not only chemical yields of cyclized products but also stereoselectivity are lower than those of the electroreductive cyclizations. 

In connection with hydride ion transfers, it will be observed that addition should occur at a positive center. Since olefin additions are usually initiated by attack at a negative center, the Meerwein-Ponndorf-Verlcy reduction should occur preferentially at the carbonyl group of unsaturated carbonyl compounds. This is actually the case both in this reaction and in reductions carried out with lithium aluminum hydride.42... 

The catalytic processes, which operate via mechanisms that cycle between Rh(I) and Rh(III) intermediates, include (1) hydrogenation (the activation of H2 for the reduction of unsaturated organic compounds), (2) hydroformylation (the activation of H2 and CO for their addition to olefins to generate aldehydes or alcohols) and (3) carbonylation (the activation of CO for its addition to organics). Some of the processes have been developed commercially. 

Carbonyl group reduction. With LiBH4 as catalyst the reduction prevails over hydroboration of unsaturated carbonyl compounds. Conjugated alkenones give allylic alcohols. 

Titanium(ii)-chloride-induced reductive cyclization of one of the photo-adducts (43) of isoprene and methyl 2,4-dioxopentanoate produced a mixture of diastereo-meric diols (44), which are useful precursors in the synthesis of iridoids. The Lewis-acid-catalysed reaction of unsaturated carbonyl compounds such as (45) shows a strong dependence on the strength and quantity of Lewis acid used. 

Due to the low oxidation state of the metal in carbonyliron complexes and ferrates, these species can be applied for the reduction of various carbonyl compounds. Initially, these reagents have been applied in stoichiometric amounts. First examples describe the hydrogenation of a,p-unsaturated carbonyl compounds by carbonyl(hydrido)ferrate complexes to give saturated carbonyl compounds or saturated alcohols. Low valent iron species for the reduction of carbonyl compounds and imines can also be generated in situ from iron(II) chloride and lithium powder in the presence of 4,4 -di-rert-butylbiphenyl. Catalytic versions have been developed subsequently. Thus, pentacarbonyliron functions as a precatalyst for the hydrogenation of aldehydes and ketones in the presence of a tertiary amine as solvent (Scheme 4-322). The catalytically active system probably consists of (tetracarbonyl)(hydrido)ferrate and the protonated amine. ... 

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. 

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