Reduction of a ketone

The reduction of a ketone by a metal hydride involves the formation of two bonds the linking of the carbonyl carbon to a hydride and the formation of a metal oxygen bond (4). 

Sometimes reduction of a ketone by NaBH4 is accompanied by hydrolysis of an ester elsewhere in the molecule. Norymberski found that a 20-keto-21-acetoxy compound with NaBH4 in methanol at 0° for 1 hour gives the 20/ ,21-diol. 50 % aqueous dimethylformamide has been used as the solvent in an attempt to prevent acetate hydrolysis, but sometimes under these conditions the 21-acetoxy group migrates to the 20-position. The rearrangement is favored by addition of the 20-acetate as seeds or by addition of... 

Identify the target alcohol as primary, secondary, or tertiary. A primary alcohol can be prepared by reduction of an aldehyde, an ester, or a carboxylic acid a secondary alcohol can be prepared by reduction of a ketone and a tertiary alcohol can t be prepared by reduction. 

The Mecrwein-Ponndoi f-Verlev reaction involves reduction of a ketone by treatment with an excess of aluminum triisopropoxide. The mechanism of the process is closely related to the Cannizzaro reaction in that a hydride ion acts as a leaving group. Propose a mechanism. 

An IL solvent system is applicable to not only lipase but also other enzymes, though examples are still limited for hpase-catalyzed reaction in a pure IL solvent. But several types of enzymatic reaction or microhe-mediated reaction have been reported in a mixed solvent of IL with water. Howarth reported Baker s yeast reduction of a ketone in a mixed solvent of [hmim] [PFg] with water (10 1) (Fig. 16). Enhanced enantioselectivity was obtained compared to the reaction in a buffer solution, while the chemical yield dropped. 

Crocq et al. (1997) have synthesized trimegestone through Bakers yeast mediated reduction of a ketone (this material is a new progestomimetic molecule for the treatment of postmenopausal diseases). The key step of the multistep synthesis is the chemo-, regio- and almost stereospecific bioreduction of a triketone to the desired alcohol. 

Aluminum ethoxide, 21, 9 Aluminum isopropoxide, 21, 9 Amalgamated zinc, 20, 57 23, 86 Amide, 20, 37, 62, 66 preparation by ammonolysis, 20, 62 Amination, by reduction of a ketone in the presence of ammonia, 23, 68 of bromoacetal with use of high-pressure hydrogenation bomb, 24, 3 of a-bromoisocaproic acid, 21, 75 of a -bromo-/3-methylvaleric acid, 21, 62... 

Dicyclohexyl Ether [Brpnsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether].313 Cyclohexanone (3.92 g, 40 mmol) and tri(n-butyl) silane (1.78 g, 20 mmol) were placed in a round-bottomed flask. TFA (75 mmol) was added slowly over a one-hour period to the reaction mixture, which was held at —35°. After complete addition, the reaction flask was placed in a freezer at —15° for 70 hours. Direct distillation gave dicyclohexyl ether 2.91 g (16 mmol, 80%) bp 119-121718 Torr. 

Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound].423 A... 

Hydroxy esters have been obtained successfully with baker s yeast (Sac-charomyces cerevisidae), and this has shown a wide scope of application. The facial selectivity in the reduction of both isolated ketones and //-keto esters can be reliably determined by using Prelog s rule,8 which predicts that the hydrogen addition by the yeast will occur from the front face (Scheme 8-2). Anti-Prelog microbial reduction of a-ketones with Geotrichum sp. 38 (G38) has been introduced by Gu et al.9... 

In 1969, Fiaud and Kagan[U1 tested ephedrine boranes but achieved only 3.6-5% enantiomeric excess in the reduction of acetophenone. Itsuno et a/.[121 reported in 1981 an interesting enantioselective reduction of a ketone using an amino alcohol-borane complex as a catalyst. Buono[131 investigated and developed the reactivity of phosphorus compounds as ligands in borane complexes for asymmetric hydrogenation. 

Scheme 19. Corey s utilization of B-methyl CBS catalyst in the asymmetric reduction of a ketone en route to wodeshiol (1999), and Nicolaou s application of the Corey technology to a total synthesis of rapa-mycin (1993).

The aforementioned deuterated derivatives were prepared by way of reduction of a ketone, aldehyde, or ester with sodium borodeu-teride, or by deuteroboration of an alkene. An interesting reaction, perhaps eventually applicable to direct deuteration of polysaccharides, was reported by Koch and Stuart413 and by them and their coworkers,41b who found that treatment of methyl a-D-glucopyranoside with Raney nickel catalyst in deuterium oxide results in exchange of protons attached to C-2, C-3, C-4, and C-6. In other compounds, some protons of CHOH groups are not replaced, but the spectra may nevertheless be interpreted with the aid of a- and /3-deuterium effects. 

A powerful method to convert non-conjugated keto olefins into cyclic alcohols [46,47] utilizes the cathodic reduction of a ketone to afford a ketyl, which subsequently undergoes cyclization onto the pendant alkene. As illustrated in Eqs. (27H30), the process provides access to mono-, bi-, and heterocyclic systems from very simple starting materials. It is especially well-suited to the construction of five-membered rings, less so for six-, and is not effective in producing seven-membered rings. 

The use of water-miscible organic solvent-water mixtures is a particularly attractive method for use with cofactor-dependent enzymes due to its simphcity. The high water content can allow dissolution of both enzyme and cofactor, whilst the water-miscible solvent can provide a dual role in both substrate dissolution and as a cosubstrate for cofactor recycling (substrate-coupled cofactor recycling).The asymmetric reduction of a ketone intermediate of montelukast using an engineered ADH in the presence of 50 % v/v isopropanol offers a powerful demonstration of this methodology (Scheme 1.55). 

In the course of some stereoselective reactions the inducing chiral unit is destroyed. A classical example is the enantioselective Meerwein Ponndorf reduction of a ketone with a chiral Grig-nard compound33 ... 

Selective reduction of ketones. Selective reduction of a ketone in the presence of an aldehyde is possible by selective reaction of the aldehyde with -bulylamine (4 A molecular sieves), reduction of the ketone with lithium tri-(-butoxyaluminum hydride, and, finally, cleavage ol the aidimine to the aldehyde with aqueous HCI. The three-step sequence can be conducted in one pot. The selectivity is high. The method is not applicable to conjugated ketones because of conjugate reduction. 

Directed asymmetric reduction of a ketone has been brought about by the use of an intramolecular homochiral boronate ester250. The latter was readily introduced at a hydroxyl group in the molecule and has allowed the production of the enantiomeric alcohol, from the ketone by use of BH3-complex as the reductant (equation 64). The boronate ester may be readily removed by treatment with hydrogen peroxide-sodium hydroxide, using standard methodology. Other similar reductions have also been reported251-253. 

The simplest method for generation of a ketyl anion is via direct reduction (chemically of electrochemically) of an aldehyde or ketone (Figure 1, reaction 1). Historically, it was via direct reduction of a ketone with an alkali metal that ketyl anions were first discovered. 

Stereoselective reduction of a ketone. The first step in a conversion of the... 

J. Buendia, and D. Prat, Synthesis of trimegestone the first industrial application of bakers yeast mediated reduction of a ketone, Org. Proc. Res. Dev. 1997, 3, 2-13. 

A is correct. Reduction of a ketone produces a secondary alcohol. In this case two ketones were reduced. You might recognize LiAJH4 as a reducing agent but you don t need to. 

In the reactions discussed and exemplified above, reactants, transient species and products are related by linear sequences of elementary reactions. The transient species can be regarded as a kinetic product and, if isolable, subject to the usual tests for stability to the reaction conditions. Multiple products, however, may also occur by a mechanism involving branching. Indeed, the case shown earlier in Fig. 9.5b, where the transient is a cul de sac species, is the one in which the branching to the thermodynamic product P and kinetic product T occurs directly from the reactant. In the absence of reversibility, the scheme becomes as that shown in Scheme 9.8a, where the stable products P and Q are formed as, for example, in the stereoselective reduction of a ketone to give diastereoisomeric alcohols. The reduction of 2-norbornanone to a mixture of exo- and cndo-2-norbornanols by sodium borohydride is a classic case. The product ratio is constant over the course of the reaction and reflects directly the ratio of rate constants for the competing reactions. The pseudo-first-order rate constant for disappearance of R is the sum of the component rate constants. 

The next step is reduction of a ketone to a secondary alcohol. Lithium aluminum hydride is suitable it reduces carbonyl groups but leaves the double bond intact. 

Reduction of substituted glycosuloses has been valuable in synthetic schemes identihcation of the two epimers obtained by reduction of a ketone has been used to locate the position of the ketone group. Steric factors influence various reducing reagents differently. A good example of stereoselectivity is found in the reduction of l,2 5,6-di-0-isopropylidene-a-i)-r/7)o-hexofuranos-3-ulose (218), which is reduced by... 

Reduction of ketones. Merck chemists3 have used oxazaborolidine-catalyzed reduction of a ketone for introduction of chirality in a synthesis of MK-927 (4), a carbonic anhydrase inhibitor. They found that even traces of water decreases the enantioselectivity in reductions of 2. Highest enantioselectivity (98 2) is obtained by... 

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