123356-14-9

Upstream product

• 108-05-4 vinyl acetate 
• 121054-03-3 2-hydroxy-4-phenylbutanenitrile 
• 108-24-7 acetic anhydride 
• 53279-92-8 (S)-2-hydroxy-4-phenylbutyronitrile 
• 104-53-0 3-phenyl-propionaldehyde 
• 75-86-5 2-hydroxy-2-methylpropanenitrile 
• 75-36-5 acetyl chloride 
• 7677-24-9 trimethylsilyl cyanide 
• 151-50-8 potassium cyanide 
• 773837-37-9 sodium cyanide 
• 335087-69-9 (S)-(-)-4-phenyl-2-(trimethylsilyloxy)butanenitrile 

Relevant academic research and scientific papers

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.

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.

Enantioselective O-acetylcyanation/cyanoformylation of aldehydes using catalysts with built-in crown ether-like motif in chiral macrocyclic V(V) salen complexes

Chiral macrocyclic V(V) salen complexes 1a-f derived from macrocyclic ligands obtained by the reaction of 1R,2R-(-) diaminocyclohexane/(1R,2R)-(+)-1, 2-diphenylethylenediamine with bis-aldehydes 2 and 3 were synthesized and used as efficient catalysts in asymmetric cyanation reactions. The V(V) catalysts demonstrated excellent performance (product yields and ees up to 99%) with potassium cyanide (KCN) and sodium cyanide (NaCN). The catalytic system also performed very well with a safer source of cyanide-ethyl cyanoformate to give cyanohydrin carbonates in excellent yield and ee (up to 97%). The V(V) macrocyclic salen complex 1b retained its performance at multi-gram level and was conveniently recycled for a number of times.

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.

Kinetic resolution of cyanohydrins via enantioselective acylation catalyzed by lipase PS-30

By using lipase PS-30 as catalyst, the kinetic resolution of a series of racemic cyanohydrins has been achieved via enantioselective acylation. The values of kinetic enantiomeric ratio (E) reached up to 314. Substituent effect is also briefly discussed.

A novel chiral (salen)AlIII complex catalyzed asymmetric cyanosilylation of aldehydes

A novel chiral (salen)AlIII complex was synthesized through the reaction of Et2AlCl and salen (R,R)-1 derived from (R,R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene. This complex is an efficient catalyst for the asymmetric trimethylsilylcyanation of aldehydes in the presence of tributylphosphane oxide as an additive. The use of 1 mol-% of the complex led to the corresponding cyanohydrins in high yields (85-94%) with good-to-excellent enantioselectivities (42-92%ee). 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.

Synthesis of the bifunctional BINOL ligands and their applications in the asymmetric additions to carbonyl compounds

Efficient one-step syntheses of the bifunctional BINOL and H8BINOL ligands (S)-6 and (S)-8 have been developed from the reaction of BINOL and H8BINOL with morpholinomethanol, respectively. The X-ray analyses of these compounds have revealed their structural similarity and difference. The bifunctional H8BINOL (S)-8 is found to be highly enantioselective for the reaction of diphenylzinc with many aliphatic and aromatic aldehydes and especially is the most enantioselective catalyst for linear aliphatic aldehydes. Unlike other catalysts developed for the diphenylzinc addition which often require the addition of a significant amount of diethylzinc with cooling (or heating) the reaction mixture in order to achieve high enantioselectivity, using (S)-8 needs no additive and gives excellent results at room temperature. (S)-8 in combination with diethylzinc and Ti(OiPr)4 can catalyze the highly enantioselective phenylacetylene addition to aromatic aldehydes. It can also promote the phenylacetylene addition to acetophenone at room temperature though the enantioselectivity is not very high yet. Without using Ti(OiPr)4 and a Lewis base additive, (S)-8 in combination with diethylzinc can catalyze the reaction of methyl propiolate with an aldehyde to form the highly functional γ-hydroxy-α,β-acetylenic esters except that the enantioselectivity is low at this stage. The bifunctional BINOL ligand (S)-6 in combination with Me2AlCl is found to be a highly enantioselective catalyst for the addition of TMSCN to both aromatic and aliphatic aldehydes.

On-step synthesis of a bifunctional BINOL ligand for the highly enantioselective cyanation of aliphatic aldehydes

(Chemical Equation Presented) An efficient one-step synthesis of the optically active bifunctional BINOL ligand (S)-3 has been developed. It was found that (S)-3 in combination with Me2AlCl is a highly enantioselective catalyst for the addition of TMSCN to aliphatic aldehydes of diverse structures and is also among the most practical ones. A remarkable positive nonlinear effect was found for this chiral ligand.