Ketone cyanohydrins from

This process presents a typical procedure applicable to preparation of cyanohydrins from ketones and aldehydes of low reactivity. l-Cyano-6-methoxy-3,4-dihydronaphthalene is useful as an intermediate for synthesis of polycyclic compounds. 

As mentioned above, the synthesis of cyanohydrins from ketones is difficult due to the unfavorable equilibrium. However, it can be achieved. When methyl ketones were treated with only 1.5 equivalents of HCN in an emulsion of citrate buffer (pH 4.0) and MTBE, the S-selective Manihot esculenta HNL catalyzed the synthesis of the corresponding cyanohydrins with good yields (85-97%) and en-antioselectivities (69-98%). The corresponding esters were then used in a second carbon-carbon bond forming reaction. Since cyanohydrins from ketones cannot be deprotonated adjacent to the nitrile group, the esters could be selectively deprotonated and then a ring closing attack on the nitrile function yielded the unsaturated lactones (Scheme 5.6). When the nitrile function was first con-... 

Scheme 5.6 HNL-catalyzed formation of cyanohydrins from ketones and their application in synthesis.

Methyl nitroacetate sodium cyanide Epimeric cyanohydrins from ketones Carbohydrate derivs. 

A new two-step procedure for the preparation of cyanohydrins from ketones is particularly useful for the synthesis of highly hindered cyanohydrins [equation (38)]. Note that potassium cyanide and trimethylsilyl chloride can be used in place of trimethylsilyl cyanide in the above reaction. ... 

In a German patent issued in 1929, Bergs described a synthesis of some 5-substituted hydantoins by treatment of aldehydes or ketones (1) with potassium cyanide, ammonium carbonate, and carbon dioxide under several atmospheres of pressure at 80°C. In 1934, Bucherer et al. isolated a hydantoin derivative as a by-product in their preparation of cyanohydrin from cyclohexanone. They subsequently discovered that hydantoins could also be formed from the reaction of cyanohydrins (e.g. 3) and ammonium carbonate at room temperature or 60-70°C either in water or in benzene. The use of carbon dioxide under pressure was not necessary for the reaction to take place. Bucherer and Lieb later found that the reaction proceeded in 50% aqueous ethanol in excellent yields for ketones and good yields for aldehydes. ... 

Very few optically active cyanohydrins, derived from ketones, are described in the literature. High diastcrcosclectivity is observed for the substrate-controlled addition of hydrocyanic acid to 17-oxosteroids27 and for the addition of trimethyl(2-propenyl)silane to optically active acyl cyanides28. The enantioselective hydrolysis of racemic ketone cyanohydrin esters with yeast cells of Pichia miso occurs with only moderate chemical yields20. 

A general method for preparing (/ )-cyanohydrins, derived from ketones, is the (/ )-oxyni-trilase-catalyzed addition of hydrocyanic acid to ketones in an organic solvent30. The (R)-cyanohydrins are obtained with good chemical yields and in high optical purity (Table 3)30. 

Table 3. (R)-Cyanohydrins by Enzymatic Formation from Ketones and Hydrocvamic Acid as well as (7 )-a-Hydroxy-a-methyl Carboxylic Acids by Hydrolysis...

The endo-spiro-OZT could be prepared through a reaction sequence similar to that applied for the exo-epimer, with spiro-aziridine intermediates replacing the key spiro-epoxides (Scheme 18). Cyanohydrin formation from ketones was tried under kinetic or thermodynamic conditions, and only reaction with the d-gluco derived keto sugar offered efficient stereoselectivity, while no selectivity was observed for reaction with the keto sugar obtained from protected D-fructose. The (R) -cyanohydrin was prepared in excellent yield under kinetic conditions (KCN, NaHC03, 0 °C, 10 min) a modified thermodynamic procedure was applied to produce the (S)-epimer in 85% yield (Scheme 18). 

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

Roberge, C., Fleitz, F., Pollard, D. and Devine, P., Synthesis of optically active cyanohydrins from aromatic ketones evidence of an increased substrate range and inverted stereoselectivity for the hydroxynitrile lyase from Linum usitatissimum. Tetrahedron Asymm., 2007,18, 208. 

The preparation of (S)-ketone cyanohydrins has also been achieved in a one-pot procedure, using the PaHnl, by decomposition of the corresponding racemic cyanohydrins followed by stereoselective addition of the HCN that is liberated to m-bromoaldehydes [97]. This tandem reaction process yielded both (S)-ke-tone cyanohydrins (from the decomposition of the racemic cyanohydrin) and (i )-m-bromocyanohydrins (the HCN addition product), the latter being con-... 

Many enzymes are both active and stable in carbon dioxide and have been used to conduct a number of reactions. Several different types of reactions have been examined, including hydrolysis (Lee et al., 1993 Randolph et al., 1985 Zheng and Tsao, 1996), oxidation (Hammond et al., 1985 Randolph et al., 1988), and esterification/transesterification (Kamihira et al., 1987 Nakamura et al., 1986 Rantakyla and Aaltonen, 1994), but there are other types of reactions that would make worthwhile investigations in carbon dioxide. These include preparation of amides, reduction of ketones, preparation of cyanohydrins from aldehydes, aldol reactions, hydroxylation reactions, and Baeyer-Villiger oxidation. 

What procedure is available for preparing an a-hydroxy acid. Answer The hydrolysis of a cyanohydrin from an aldehyde or ketone wili yield an a-hydroxy acid. 

Cyanohydrins from the attack of cyanide on aldehydes and ketones... 

Cyanohydrins are versatile building blocks that are used in both the pharmaceutical and agrochemical industries [2-9]. Consequently their enantioselective synthesis has attracted considerable attention (Scheme 5.1). Their preparation by the addition of HCN to an aldehyde or a ketone is 100% atom efficient. It is, however, an equilibrium reaction. The racemic addition of HCN is base-catalyzed, thus the enantioselective, enzymatic cyanide addition should be performed under mildly acidic conditions to suppress the undesired background reaction. While the formation of cyanohydrins from aldehydes proceeds readily, the equilibrium for ketones lies on the side of the starting materials. The latter reaction can therefore only be performed successfully by either bio- or chemo-cat-... 

Chiral cyanohydrins of ketones are prepared from aldehyde cyanohydrins by reaction with 18 and alkylation of the phosphoryl derivatives. ... 

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