197852-02-1

Upstream product

• 3446-58-0 3-oxo-3-phenylpropanamide 
• 614-16-4 Benzoylacetonitrile 
• 1191104-09-2 3-phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propanamide 
• 132203-26-0 (S)-3-hydroxy-3-phenylpropanenitrile 

Downstream Products

• 96854-34-1 (S)-3-phenyl-1,3-propanediol 
• 33401-74-0 ethyl (3R)-3-hydroxy-3-phenylpropionate 
• 36567-72-3 (S)-3-hydroxy-3-phenylpropanoic acid 

Relevant academic research and scientific papers

Strengthening the Combination between Enzymes and Metals in Aqueous Medium: Concurrent Ruthenium-Catalyzed Nitrile Hydration - Asymmetric Ketone Bioreduction

A dual ruthenium/ketoreductase catalytic system has been developed for the conversion of β-ketonitriles into optically active β-hydroxyamides through an unprecedented hydration/bioreduction cascade process in aqueous medium working in concurrent mode. The ketoreductase-mediated ketone reduction took place with exquisite stereoselectivity and it was simultaneous to the nitrile hydration promoted by the ruthenium catalyst. The overall transformation occurred: (i) employing commercially and readily available catalytic systems (ii) under mild reaction conditions, (iii) with high degree of conversion and excellent stereoselectivity, and (iv) without the need to isolate intermediates and with high final product yields. This genuine process demonstrates the benefits of combining metal and enzymatic catalysis to tackle the limitations arising from each field.

Heterogeneous versus homogeneous copper(II) catalysis in enantioselective conjugate-addition reactions of boron in water

We have developed CuII-catalyzed enantioselective conjugate-addition reactions of boron to α,β-unsaturated carbonyl compounds and α,β,γ,δ-unsaturated carbonyl compounds in water. In contrast to the previously reported CuI catalysis that required organic solvents, chiral CuII catalysis was found to proceed efficiently in water. Three catalyst systems have been exploited: cat. 1: Cu(OH)2 with chiral ligand L1; cat. 2: Cu(OH)2 and acetic acid with ligand L1; and cat. 3: Cu(OAc)2 with ligand L1. Whereas cat. 1 is a heterogeneous system, cat. 2 and cat. 3 are homogeneous systems. We tested 27 α,β-unsaturated carbonyl compounds and an α,β-unsaturated nitrile compound, including acyclic and cyclic α,β-unsaturated ketones, acyclic and cyclic β,β- disubstituted enones, acyclic and cyclic α,β-unsaturated esters (including their β,β-disubstituted forms), and acyclic α,β-unsaturated amides (including their β,β-disubstituted forms). We found that cat. 2 and cat. 3 showed high yields and enantioselectivities for almost all substrates. Notably, no catalysts that can tolerate all of these substrates with high yields and high enantioselectivities have been reported for the conjugate addition of boron. Heterogeneous cat. 1 also gave high yields and enantioselectivities with some substrates and also gave the highest TOF (43 200 h-1) for an asymmetric conjugate-addition reaction of boron. In addition, the catalyst systems were also applicable to the conjugate addition of boron to α,β,γ, δ-unsaturated carbonyl compounds, although such reactions have previously been very limited in the literature, even in organic solvents. 1,4-Addition products were obtained in high yields and enantioselectivities in the reactions of acyclic α,β,γ,δ-unsaturated carbonyl compounds with diboron 2 by using cat. 1, cat. 2, or cat. 3. On the other hand, in the reactions of cyclic α,β,γ,δ-unsaturated carbonyl compounds with compound 2, whereas 1,4-addition products were exclusively obtained by using cat. 2 or cat. 3, 1,6-addition products were exclusively produced by using cat. 1. Similar unique reactivities and selectivities were also shown in the reactions of cyclic trienones. Finally, the reaction mechanisms of these unique conjugate-addition reactions in water were investigated and we propose stereochemical models that are supported by X-ray crystallography and MS (ESI) analysis. Although the role of water has not been completely revealed, water is expected to be effective in the activation of a borylcopper(II) intermediate and a protonation event subsequent to the nucleophilic addition step, thereby leading to overwhelmingly high catalytic turnover. Copyright

Chiral iridium catalysts bearing spiro pyridine-aminophosphine ligands enable highly efficient asymmetric hydrogenation of β-aryl β-ketoesters

Tons of TONs: Chiral iridium catalysts bearing ligand 1 are highly efficient for the asymmetric hydrogenation of β-substituted β-ketoesters. The product β-hydroxyesters are delivered in high yield with excellent enantioselectivities and high turnover numbers (TONs). cod= 1,5-cyclooctadiene.

Chemoenzymatic synthesis2 of both enantiomers of fluoxetine, tomoxetine and nisoxetine: Lipase-catalyzed resolution of 3-aryl-3-hydroxypropanenitriles

A facile preparation of (±)-3-hydroxy-3-phenylpropanenitrile has been carried out by ring-opening of styrene oxide with NaCN in aqueous ethanol. Subsequent kinetic resolution of this material via lipase-mediated transesterification gave the S-alcohol and R-acetate in excellent yields and high enantioselectivities, particularly with lipase PS-C 'Amano' II. The effect of solvents and immobilization of the lipase has also been investigated. It is interesting to note that the use of immobilized lipase for this transesterification process in hydrophobic solvents (diisopropyl ether, toluene and hexane) enhanced the reaction rate drastically and gave optimal yields with high enantioselectivity (>99%). Moreover, enantiopure 3-hydroxy-3-phenylpropanenitrile products have been converted via enantioconvergent routes into the (R)- and (S)-enantiomers of the important anti-depressants fluoxetine, tomoxetine, nisoxetine and norfluoxetine.

Enantioselective reduction of β-keto amides by the fungus Mortierella isabellina

Incubations of the fungus Mortierella isabellina NRRL 1757 with 3-oxo-3-phenylpropanamide, 3-oxobutanamide and with some of their N-alkyl derivatives afford the corresponding (S)-3-hydroxyamides usually in high chemical yields and enantiomeric excesses.