O-Hydroxynitriles

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 12311.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to o-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The a-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Reactions of diazo compounds with nickel carbonyl s. 16, 847 Nickel sulfatejpotassium cyanide o-Hydroxynitriles from diazo oxides... 

Nickel sulfate potassium cyanide o-Hydroxynitriles from diazo oxides... 

Condensation of the anion obtained on reaction of acetonitrile with sodium amide, with o-chlorobenzophenone (36), affords the hydroxynitrile, 37. Catalytic reduction leads to the corresponding amino alcohol (note that the benzhydryl alcohol is not hydrogenolyzed). Reductive alkylation with formaldehyde and hydrogen in the presence of Raney nickel gives the antitussive a-gent, chlorphedianol (39). °... 

The different steric hindrance of hydroxyl groups in (3R)- and (3S)-cyanohydrins was revealed by activation of a-hydroxynitriles through O-tosylation to afford the (R)-tosylate in 85% yield and the (S)-tosylate in... 

In a second approach hydrocyanic acid was added to hydroxypivaldehyde by use of (R)-selective hydroxynitrile lyase from almonds (PaHNL) [11]. (R)-Cyanohydrin was obtained in 84% yield and 89% ee, and was directly cydized to give crude D-pantolactone by acid-catalyzed hydrolysis. Unfortunately, in contrast with O-protected hydroxy and halogenated pivalaldehydes, the technically available starting compound hydroxypivaldehyde requires use of purified enzyme (and high enzyme loading). 

In the introduction to Chapter 9, it was mentioned that cyanide ions behave towards carbonyl compounds like the majority of O-, S- and Nnucleophiles. They add to the C=0 double bond. By taking up a proton the carbonyl oxygen is transformed into the OH group of a so-called cyanohydrin, i.e., a hydroxynitrile with geminal OH- and C=N groups. The classical transformation of this type is is effected by treatment of a carbonyl compound with both sodium... 

The bienzymatic approach described above could also be advantageously applied to the synthesis of (R)-2-hydroxycarboxylic acids in cases where no satisfactorily enantioselective nitrilase is available (Figure 16.5). The best enantioselectivity in the hydrolysis of lb, for example, was 92% ee. The enantioselectivity of the hydroxynitrile lyase from ahnonds (PaHnL) in the synthesis of lb is also less then perfect [13], but we found that a combiCLEA of PaHnL and NIT-106 quantitatively converted 2b (O.IM starting concentration) into 3b with ee>99% R (reaction in 90 10 DlPE-buffer pH 5.5, as before) with very little (>3%) amide formation. 

An electrocatalytic method for the reductive N-O bond cleavage of 3-methoxyisoxazoline in the presence of Ni bpy was studied. The nickel complex, generated in situ, acts as the actual electron source. Under these conditions, isoxazoline 59 afforded a mixture of p-hydroxyester 60 and p-hydroxynitrile 61 in high overall yields, and in different ratios depending on the amount of Ni°bpy used <03TL8217>. 

The use of the An diene participation of vinyinitroso compounds in Diels-Alder reactions in the preparation of aryl pyruvate oximes, amino acids, y-hydroxynitriles,y-lactones, pyridine N-o -ides, and pyrroles is summarized in Scheme 9-III. The intramolecular Diels-AIder reactions of in situ generated and unactivated vinyinitroso compounds have been shown to proceed readily employing electron-rich olefins, and the course of the reaction has been shown to proceed preferentially through an endo transition state [Eq. (36)]. ... 

Aminoacid (o-threonine, L-aspartic) and hydroxyacid (L-tartaric, L-lactic) derivatives were repeatedly employed in the past as chiral substrates in the synthesis of daunosamine. More recently, protected L-lactaldehyde was used for the same purpose. Stereospecific synthesis of intermediate diol 95 was achieved with help of the enzyme (R)-hydroxynitrile lyase, which... 

Ethylenenitriles. POCI3 added to a soln. of the startg. hydroxynitrile in methylene diloride, and heated 20 min. rranj-/5-ferrocenyl-o-cyanostyrene. Y ca. 100%. Also a,/5-ethylenenitriles s. A. A. Koridze and S. P. Gubin, J. Organometal. Chem. 22, 157 (1970) without solvent, franj-stilbenes, s. C. G. Joshi, J. L. Bose, and R. C. Shah, Indian J. Chem. 8, 141 (1970). 

New or improved syntheses of a-aminonitriles, jS-aminonitriles, optically active O-acetylcyanohydrins, syn-/3-hydroxynitriles, and y-hydroxynitriles have also been reported. 

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