Cyanohydrins epimerization

Steroids possessing an epoxide grouping in the side chain have likewise been converted to fluorohydrins. Thus, 20-cyano-17,20-epoxides of structure (19) furnish the 17a-fluoro-20-ketones (20) after treatment of the intermediate cyanohydrins with boiling collidine. The epimeric 5a,6a 20,21-oxides (21) afford the expected bis-fluorohydrins (22). The reaction of the allylic... 

While both possible epimeric cyanohydrins are formed (with the 17a-cyano-17/9-hydroxy compound predominating) the mixture can be used in the dehydration step, which destroys the asymmetry. 

Cyanoandrost-5-ene-3jS,17-diol 3-Acetate Acetic acid (385 ml) is added during a 40 min period at 10° to a stirred mixture of 60 g of 3) -liydroxy-androst-5-en-17-one acetate and 360 g of potassium cyanide in 2 liters of alcohol. The mixture is stirred for 1 hr at 10° and then for 2 hr at room temperature. After dilution with water the precipitated product is collected by filtration, washed with 3 liters of 2 % acetic acid and dried at room temperature. The yield of epimeric cyanohydrins (mp 124° dec [ajj, —93°) is essentially quantitative. 

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

The synthesis of " C-labelled o-glucose starts with the pentose o-arabinose and " C-labelled potassium cyanide, which react together to form a cyanohydrin (see Section 7.6.1). Since cyanide can attack the planar carbonyl group from either side, the cyanohydrin product will be a mixture of two diastereoisomers that are epimeric at the new chiral centre. The two epimers are usually formed in unequal amounts because of a chiral influence from the rest of the arabinose structure during attack of the nucleophile. 

About one-half of the product-weiglit could not be recovered in chromatograpliy of the reductive-amination mixture, and more work is clearly needed to unravel the complexity of the process. Thus far, 4 minor byproducts were isolated crystalline in yields of 1.5—3%. All possessed one 3-acetamido-3-deoxy-X-D-altro residue, in common with 91, but were not aminated in the second residue. Two of them were epi-meric 3 -carbinols resulting from nonaminative reduction, and the other two were epimeric 3 -cyanohydrins. 

The reaction of 3/3-acetoxy-5a-cholest-8(14)-en-7-one with EtjAlCN was the key reaction in a synthesis of cholestanes containing an oxygenated 14a-substi-tuent. Cholest-4-en-3-one reacted smoothly with KCN-acetone cyanohydrin in benzene or acetonitrile containing 18-crown-6 to give the epimeric 5-cyano-cholestan-3-ones. An 11 -hydroxy-group increased the proportion of a-epox-ide produced in the reaction of 3-oxo-A -steroids with H202-0H . A 9a-fluorine substituent also influenced the stereochemistry of the reaction products and a... 

On applying the Kiliani cyanohydrin synthesis to 2 deoxy-i>-erythro-pentose, Wood and Fletcher127 obtained crystalline 3-deoxy-D-ribo-hexose and 3-deoxy-D-arabino-hexose (as the dithioacetal). Interesting comments concerning the course of the Kiliani synthesis were made by these authors. Condensation127 of 2-deoxy-D-erj/(Aro-pentose with nitromethane gave epimeric 1,3-didcoxy-l-nitrohexitols which, after hydrolysis under Nef... 

S)-proline-catalyzed reactions using unmodified aldehydes as nucleophiles retain the aldehyde group, and the aldehyde group of the products can be used for further transformations in the same reaction vessel. For example, one-pot Mannich-oxime formation [71b], Mannich-allylation [71c], and Mannich-cyanation [80] reactions have been demonstrated (Scheme 2.18). Mannich-type reaction products that possess an aldehyde functionality are easily epimerized during work-up and silica gel column purification. In the one-pot Mannich-cyanation reaction sequence, the cyanohydrin was obtained without epimerization at the a-position of the original aldehyde Mannich products. Thus, this one-pot sequence minimizes potential epimerization of the Mannich products. 

The aldehyde carbon atom is made asymmetric in the first step with the formation of the cyanohydrin. Two epimeric cyanohydrins result. For example, D-arabinose reacts with HCN to give the following cyanohydrins. 

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