Hydrocyanation, asymmetric

As early as 1908, Rosenthaler found in the ferment mixture of emulsin a u-oxynitrilase , which directed the addition of hydrocyanic acid (hydrogen cyanide) to benzaldehyde asymmetrically to give x-hydroxybenzeneacetonitrilc (mandelonitrile)9. This result was confirmed1 °, however, it was not until 1963 that Pfeil ct al. first isolated and characterized the enzyme (R)-oxyni-trilase [EC 4.1.2.101 from bitter almonds (Prunus amygdalus)1 12. The yellow-colored enzyme contains a flavin-adenine dinucleotide (FAD)11 and loses its activity by splitting off this prosthet-... 

Table 6 The effect of substituents in carbohydrate phosphine (28) on the asymmetric hydrocyanation of 2-methoxy-6-vinylnaphthalene.

RajanBabu, T. V. Casalnuovo, A. L. Hydrocyanation of Carbon-Carbon Double Bonds. In Comprehensive Asymmetric Catalysis Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds. Springer-Verlag Berlin, 1999 pp 367-378. 

Nitrations Green sources of electophlllc nitrogen (not TsNj, nitroso, or dllmide) Asymmetric hydrocyanation... 

Chen, P., Han, S., Lin, G., Huang, H. and Li, Z., A study of asymmetric hydrocyanation of heteroaryl carboxaldehydes catalyzed by (i )-oxynitrilase under micro-aqueous conditions. Tetrahedron Asymm., 2001,12, 3273. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

The asymmetric catalytic Pauson-Khand reaction met success in the late 1990s. Not only the conventional Co catalyst but also other metal complexes, such as Ti, Rh, and Ir, are applicable to the reaction. Asymmetric hydrocyanation of vinylar-enes is accomplished using Ni complex of chiral diphosphite. Further studies on the scope and limitation are expected. 

Recently, Kunz et al. reported a new organocatalyst for the asymmetric Strecker reaction [132]. The paracyclophane-derived imine catalyst (280) promotes the hydrocyanation of various imines, both aromatic and aliphatic (Scheme 79). 

Fig. 11 Kunz s hypothesized pre-transition state for the asymmetric hydrocyanation of imines promoted by a novel paracyclophane imine catalyst...

Firstly, we examined the asymmetric hydrocyanation of 3-phenylpropanal. When 3-phenylpropanal was treated with cyanotrimethylsilane using the chiral titanium alkoxide prepared from dichlorodiisopropoxytitanium and the chiral 1,4-diol 17b in toluene at room temperature, only a trace amount of the... 

Table 8. Asymmetric Hydrocyanation of Aldehydes with Cyanotrimethylsilane...

In other work, Rueping has described the asymmetric hydrocyanation of a variety of aromahc aldimines mediated by phosphoric acid Iq (Scheme 5.22) [37]. 

While all of the aryl imine substrates examined for this Strecker methodology existed predominantly or exclusively as the E-isomers, this did not appear to be a requirement for high enantioselectivity as demonstrated in the asymmetric 42-cat-alyzed (2 mol% loading) hydrocyanation of the cyclic Z-imine 3,4-dihydroisoquino-line, which was converted to the corresponding adduct (88% yield, 91% cc) with the same sense of stereoinduction with respect to the benzylic stereogenic center as the examined acyclic E-imines (Schemes 6.41 and 6.42) [196]. 

When an aldehyde is allowed to react with an optically active amine and hydrocyanic acid, one of the two diastereomeric amino nitriles, (124a) or (124b), may be formed in excess. To prepare the chiral amino acids (125a) or (125b), the nitriles (124a) and (124b), respectively, are hydrolyzed with mineral acids, whereupon R is split off. However, this asymmetric synthesis of amino acids has no industrial significance. 

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