53279-92-8

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 41, p. 740, 1976 DOI: 10.1021/jo00866a048

Upstream product

• 104-53-0 3-phenyl-propionaldehyde 
• 7677-24-9 trimethylsilyl cyanide 
• 151-50-8 potassium cyanide 
• 121054-03-3 2-hydroxy-4-phenylbutanenitrile 
• 2043-61-0 cyclohexanecarbaldehyde 
• 74-90-8 hydrogen cyanide 
• 119798-23-1 acetic acid 1-cyano-3-phenylpropyl ester 
• 335087-69-9 (S)-(-)-4-phenyl-2-(trimethylsilyloxy)butanenitrile 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 99902-37-1 (3R,5R)-5-carbamoyl-3-methyl-7-phenyl-4-oxaheptansaeure 
• 108-05-4 vinyl acetate 

Downstream Products

• 123356-14-9 (S)-2-acetyloxy-4-phenylbutanenitrile 
• 1050264-88-4 (S)-1-cyano-3-phenylpropyl diisopropylcarbamate 
• 1364488-12-9 (R)-2-cyano-1-ethoxy-1-oxo-4-phenylbutan-2-yl pyrrolidine-1-carboxylate 
• 1364488-16-3 (R)-3-cyano-5,5-dimethyl-4-oxo-1-phenylhexan-3-yl dimethylcarbamate 
• 1364488-15-2 (R)-3-cyano-5-methyl-4-oxo-1-phenylhexan-3-yl dimethylcarbamate 
• 1379661-90-1 (R)-3-cyano-4-oxo-1-phenylheptan-3-yl dimethylcarbamate 
• 1364488-14-1 (R)-2-cyano-1-oxo-1,4-diphenylbutan-2-yl dimethylcarbamate 
• 1364488-11-8 (R)-ethyl 2-cyano-2-((diethylcarbamoyl)oxy)-4-phenylbutanoate 
• 1364488-09-4 (R)-ethyl 2-cyano-2-((diisopropylcarbamoyl)oxy)-4-phenylbutanoate 
• 1364488-10-7 (R)-ethyl 2-cyano-2-((dimethylcarbamoyl)oxy)-4-phenylbutanoate 

Relevant academic research and scientific papers

Metallation–substitution of an α-oxygenated chiral nitrile

Deprotonation of a chiral alpha-oxygenated nitrile with the base 2,2,6,6-tetramethylpiperidylmagnesium chloride, TMPMgCl, gives rise to a chiral magnesiated nitrile, and this anion has sufficient configurational stability at low temperature to allow the formation of highly enantiomerically enriched substituted nitrile products after electrophilic quench.

Improving the properties of bacterial r-selective hydroxynitrile lyases for industrial applications

Hydroxynitrile lyases (HNLs) catalyse the reversible cleavage of cyanohydrins to carbonyl compounds and HCN. The recent discovery of bacterial HNLs with a cupin fold gave rise to a new promising class of these enzymes. They are interesting candidates for the synthesis of cyanohydrins on an industrial scale owing to their high expression levels in Escherichia coli. The activity and enantioselectivity of the manganese-dependent HNL from Granulicella tundricola (GtHNL) were significantly improved by site-saturation mutagenesis of active site amino acids. The combination of beneficial mutations resulted in a variant with 490-fold higher specific activity in comparison to the wild-type enzyme. More importantly, GtHNL-A40H/V42T/Q110H is a highly competitive alternative for the synthesis of chiral cyanohydrins, such as 2-chlorobenzaldehyde cyanohydrin, (R)-2-hydroxy-4-phenylbutyronitrile, and (R)-2-hydroxy-4-phenyl-3-butene nitrile, which serve as intermediates for the synthesis of pharmaceuticals.

(R)-selective hydroxynitrile lyase variants with a cupin fold having improved substrate scope and the use thereof

The present invention relates to an improved recombinant cupin-hydroxynitrile lyase (HNL), which is capable to catalyze the asymmetric cyanohydrin reaction, wherein the recombinant cupin-HNL comprises at least one amino acid substitution, preferably at le

Chemoenzymatic flow cascade for the synthesis of protected mandelonitrile derivatives

A chemoenzymatic two-step cascade process, with both steps having incompatible reaction conditions, was successfully performed in continuous flow. The chemoenzymatic aqueous formation of cyanohydrins was integrated with a subsequent organic phase protection step in a single flow process utilising a membrane-based phase separation module. The wider applicability of our setup was demonstrated with the synthesis of nine protected cyanohydrin derivatives, all obtained in good yields and high to excellent enantioselectivity.

Room-temperature synthesis of enantioenriched non-protected cyanohydrins using vanadium(salalen) catalyst

Room-temperature synthesis of enantioenriched non-protected cyanohydrins using acetone cyanohydrin as the cyanide source was achieved by V(salalen) catalyst. Aliphatic aldehydes underwent the cyanation with 89-95% ee in the presence of only 0.2-0.4 mol% catalyst. Aromatic cyanohydrins were also obtained in high enantiomeric excesses under modified conditions.

Enzymatic kinetic resolution of racemic cyanohydrins via enantioselective acylation

Enzymatic kinetic resolution of a series of aromatic and aliphatic cyanohydrins in organic media has been investigated. The behavior of potential lipases, molecular sieves, acyl reagent, reaction temperature, and organic solvents on the kinetic resolution was studied. The influence of substrate structure, steric, and electronic nature and position of the aryl substituent on the enantioselectivity was discussed. Under the optimized reaction conditions, good enantioselectivity could be achieved for most of the investigated compounds. Specifically, substrates 1a, 1c, 1d, 1f, 1u could be resolved with the kinetic enantiomer ratio (E) higher than 200.

Asymmetric synthesis of a new salen type-titanium complex as the catalyst for asymmetric trimethylsilylcyanation of aldehydes

This work describes the asymmetric synthesis of a new salen-type ligand via a Diels-Alder reaction and Curtius rearrangement. The ligand with a norbornane skeleton was used in the trimethylsilylcyanation of aldehydes, but the enantioselectivity was 55%ee. The norborane skeleton was cleaved to destroy this rigidity, and the eanatioselectivity was thereby increased to 85%ee.

Chirality transfer from epoxide to carbanion: Base-induced alkylation of O-carbamoyl cyanohydrins of β-silyl-α,β-epoxy aldehyde

Enantioselective C-C bond formation at an α-position of a nitrile group with an external electrophile can be realized, although in modest ee, with the aid of both the concerted process of an epoxysilane rearrangement and a carbamoyl group. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

A new strategy for designing non-C2-symmetric monometallic bifunctional catalysts and their application in enantioselective cyanation of aldehydes

A monometallic bifunctional catalyst, in which only one imidazolyl moiety is directly attached at the 3-position of a binaphthol moiety, has been developed. The ligand (R)-1, which lacks C2-symmetry and flexible linkers, in combination with Ti(OiPr)4, has been demonstrated to promote the enantioselective cyanation of aldehydes with trimethylsilylcyanide (TMSCN), giving excellent enantioselectivities of up to 98 % ee and high yields of up to 99%. The use of this bifunctional catalytic system obviates the need for additives and is extremely simple as the reagents are added in one portion at the beginning of the reaction. The protocol has been found to tolerate a relatively wide range of aldehydes when 10 mol% of the (R)-1/Ti(OiPr) 4 complex is deployed in CH2Cl2 at -40°C, the conditions which proved most practical and effective. The asymmetric cyanations also proceeded with lower catalyst loadings (5 mol%, or even 2 mol%), still giving satisfactory enantiomeric excesses and yields. Interestingly, the use of freshly distilled TMSCN dried over CaH2 gave a low enantioselectivity and only a moderate yield of the adduct as compared with direct use of the commercial reagent. The results of 13C NMR spectroscopic studies implicate HCN as the actual reactive nucleophile.

Vanadium-catalyzed asymmetric transcyanation of aliphatic aldehydes with acetone cyanohydrin

The vanadium(V)(salalen) complex prepared in situ from the corresponding vanadium(IV) complex 4 under aerobic conditions was found to be an excellent catalyst for asymmetric transcyanation of aliphatic aldehydes with acetone cyanohydrin as the cyanide sou