Aromatic cyanohydrin acetates

Table 11.1-20). A very good illustration for the potential of enantiomer-differentiating acylation catalyzed by lipases is provided by the high-yield synthesis of a series of aromatic cyanohydrin acetates (la-g) from aldehydes, acetone cyanohydrin and vinyl acetate in the presence of Pseudomonas cepacia lipase and a basic anion-exchange resin in diisopropyl ether which proceeds under kinetic resolution coupled with in situ formation and racemization of the cyanohydrin representing a dynamic kinetic resolution. For further examples see Table 11.1-24. 

Cyanohydrins eliminate HCN under basic conditions, giving the corresponding planar aldehyde or ketone. When combined with an asymmetric reaction, the equilibrium can be used for an efficient in situ racemization of cyanohydrins, leading to a DKR process. For example, chiral secondary cyanohydrins can be acylated by isopropenyl acetate in the presence of lipase and solid base such as anion-exchange resin (OH" form) [8a,b] or silica-supported ammonium hydroxide [8c] (Scheme 5.31). A range of aromatic cyanohydrin acetates can be obtained in high chemical and optical yields, although the efficiency is lower for aliphatic precursors [8a]. The success of DKR is ascribable not only to the stereochemical... 

This methodology was employed to prepare many heterocyclic cyanohydrin acetates in high yields and with excellent enantioselectivities, Candida antarctica lipase A (CAL-A) being the lipase of choice (Scheme 5.7) [23]. A recent detailed study of the reaction conditions revealed that the carrier on which the lipase is immobilised is important generally Celite should be used for aromatic substrates. With Celite R-633 as support for Candida antarctica lipase B (CAL-B)... 

The immobilized lipase from Pseudomonas cepacia (Amano) afforded good en-antioselectivities for the formation of a range of cyanohydrin acetates derived from aromatic aldehydes (Fig. 9-5). Polymer-supported quinidine could also be employed... 

A series of cyanohydrin acetates with an e.e. up to 98% has been prepared by enzymatic hydrolysis of their racemic acetates in the presence of an esterase from Pseudomonas spJ137]. Lipoprotein lipase from Pseudomonas sp. catalysed irreversible transesterification using enol esters was applied to the resolution of different aromatic cyanohydrins[138> 139). 

Lipases were used in organic medium for the resolution of several aliphatic and aromatic cyanohydrins (Scheme 4.8). The study demonstrated the impact of molecular sieves, different acyl donors, temperature and variable organic solvents. High enantioselectivities (E > 200) were obtained using lipase PS-30 in the presence of 4 A molecular sieves, diethyl ether as solvent at 15 °C and vinyl acetate as acyl donor [13]. 

P-Cyclodextrin is also an enantioselective catalyst for HCN-additions on some aromatic aldehydes, but not in the case of 3-phenoxy benzaldehyde [651]. Recently the enzymatic enantioselective cleavage of S-cyanohydrine acetate by lipases from bacteria or Candida cylindrica [652] has [653] been claimed in a patent. Similarly, the optically active S-3-phenoxy-4-fluorobenzaldehyde cyanohydrine 301 can also be prepared by these esteratic methods, preferentially at a pn between 3.5 and 6.0 [654, 655]. Optically active cyanohydrines must be stabilized e.g. by alkanephosphonic acids [646], to inhibit slow racemization, even in the absence of bases. 

When allylic compounds are treated with Pd(0) catalyst in the absence of any nucleophile, 1,4-elimination is a sole reaction path, as shown by 492, and conjugated dienes are formed as a mixture of E and Z isomers[329]. From terminal allylic compounds, terminal conjugated dienes are formed. The reaction has been applied to the syntheses of a pheromone, 12-acetoxy-1,3-dode-cadiene (493)[330], ambergris fragrance[331], and aklavinone[332]. Selective elimination of the acetate of the cyanohydrin 494 derived from 2-nonenal is a key reaction for the formation of the 1,3-diene unit in pellitorine (495)[333], Facile aromatization occurs by bis-elimination of the l,4-diacetoxy-2-cyclohex-ene 496[334],... 

A synthesis of nitriles from the cyanohydrins of aromatic aldehydes via the reduction of the corresponding a-halo cyanides has been proposed. As an example, benzaldehyde cyanohydrin is converted by the action of thionyl chloride to phenylchloroacetonitrile (80%). This substance is reduced with zinc in acetic acid to phenylacetonitrile (70%). ... 

A variety of aldehydes—aliphatic, aromatic, and heterocyclic—have been condensed with hydantoin. Sodium acetate in a mixture of acetic acid and acetic anhydride as well as pyridine containing traces of piperidine serves as condensing agent. Reduction of the double bond is accomplished with phosphorus and hydriodic acid, ammonium sulfide, or stannous chloride, In a more recent modification, the hydantoins are synthesized from aldehyde or ketone cyanohydrins and ammonium... 

When certain cyclodipeptides are used as catalysts for the enantioselective formation of cyanohydrins, an autocatalytic improvement of selectivity is observed in the presence of chiral hydrocyanation products [80]. A commercial process for the manufacture of a pyrethroid insecticide involving asymmetric addition of HCN to an aromatic aldehyde in the presence of a cyclic dipeptide has been described [80]. Besides HCN itself, acetone cyanohydrin is also used (usually in the literature referred to as the Nazarov method), which can be activated cata-lytically by certain lanthanide complexes [81]. Acetylcyanation of aldehydes is described with samarium-based catalysts in the presence of isopropenyl acetate cyclohexanone oxime acetate is hydrocyanated with acetone cyanohydrin as the HCN source in the presence of these catalytic systems [82]. 

Trimethylsilyl [ C]cyanide is conveniently accessible from trimethylsilyl chloride, Na CN and Nal in the presence of lutidine or pyridine ". In carbon-14 synthesis it is normally generated in situ and used immediately in subsequent Lewis acid catalyzed chemical transformations. It is useful for some reactions in which alkah metal [ " C]cyanides normally fail, such as cyanide addition to acetals and aromatic and heteroaromatic aldehydes and ketones. Examples include the Znl2-catalyzed addition of TMS " CN to 2-furaldehyde followed by hydride reduction of the resultant silylated cyanohydrin to the aminoalcohol 96 " and the SnCLj-catalyzed formation of D-[l- " C]allonitrile 98, obtained from reaction of TMS " CN to the 0-acetylated hemiacetal 97 (Figure 7.26). Subsequent addition of H2Se to the nitrile group, cyclocondensation of the intermediate selenoamide in situ with ethyl bromopymvate and deprotection yielded 99, precursor to [2- " C]CI-935, a compound with... 

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