26164-15-8

Upstream product

• 186581-53-3 diazomethane 
• 4286-15-1 (S)-2-phenylbutyric acid 
• 2294-71-5 methyl 2-phenylbutanoate 
• 74-88-4 methyl iodide 
• 67-56-1 methanol 
• 167476-42-8 1,1-bis(trimethylsilyloxy)-2-phenylbutene 
• 20452-67-9 phenylethylketene 
• 392668-22-3 (+)-(2S,3S)-methyl 2-phenyl-3-(2-trimethylsilylphenylsulfanyl)butanoate 
• 495-40-9 propiophenone 
• 149-73-5 trimethyl orthoformate 
• 938-79-4 (2R)-2-phenylbutanoic acid 
• 75-75-2 methanesulfonic acid 
• 1268613-70-2 C₁₈H₁₇N₃O 
• 1268613-71-3 C₁₂H₁₃N₃O 

Downstream Products

• 4286-15-1 (S)-2-phenylbutyric acid 
• 42307-60-8 (S)-2-methylbutanal 
• 6957-17-1 (S)-4-phenyl-hexan-3-one 
• 40473-35-6 (S)-(+)-2-phenylbutyric acid chloride 

Relevant academic research and scientific papers

Design of Hemilabile N,N,N-Ligands in Copper-Catalyzed Enantioconvergent Radical Cross-Coupling of Benzyl/Propargyl Halides with Alkenylboronate Esters

The enantioconvergent radical C(sp3)-C(sp2) cross-coupling of alkyl halides with alkenylboronate esters is an appealing tool in the assembly of synthetically valuable enantioenriched alkenes owing to the ready availability, low toxicity, and air/moisture stability of alkenylboronate esters. Here, we report a copper/chiral N,N,N-ligand catalytic system for the enantioconvergent cross-coupling of benzyl/propargyl halides with alkenylboronate esters (>80 examples) with good functional group tolerance. The key to the success is the rational design of hemilabile N,N,N-ligands by mounting steric hindrance at the ortho position of one coordinating quinoline ring. Thus, the newly designed ligand could not only promote the radical cross-coupling process in the tridentate form but also deliver enantiocontrol over highly reactive alkyl radicals in the bidentate form. Facile follow-up transformations highlight its potential utility in the synthesis of various enantioenriched building blocks as well as in the late-stage functionalization for drug discovery.

Modeling and optimization of lipase-catalyzed hydrolysis for production of (S)-2-phenylbutyric acid enhanced by hydroxyethyl-β-cyclodextrin

An efficient reactive system was established to produce (S)-2-phenylbutyric acid (2-PBA) through the enzymatic enantioselective hydrolysis of 2-phenylbutyrate ester (2-PBAE) in aqueous medium. Lipase CALA from Canadian antarctica and hexyl 2-phenylbutyrate (2-PBAHE) were identified upon screening as the best enzyme and substrate, respectively. Adding hydroxyethyl-β-cyclodextrin (HE-β-CD) to improve the solubility of the substrate resulted in a 1.5 times increase in substrate conversion while retaining a high enantioselectivity compared with that when HE-β-CD was not added. The effects of lipase concentration, substrate concentration and HE-β-CD concentration, temperature, pH, and reaction time on enantiomeric excess and conversion rate were investigated, and the optimal conditions were identified using response surface methodology (RSM). Under the optimal conditions, namely 50 mg/mL lipase CALA, 30 mmol/L substrate, 60 mmol/L HE-β-CD, pH of 6.5, temperature of 83 °C and reaction time of 18 h, the enantiomeric excess and overall conversion rate were 96.05% and 27.28%, respectively. This work provides an efficient alternative method for improving the conversion of aromatic ester substrates by including β-cyclodextrin in an aqueous hydrolysis reaction system.

Enantioselective Copper-Catalyzed Defluoroalkylation Using Arylboronate-Activated Alkyl Grignard Reagents

A copper-catalyzed system has been introduced for the enantioselective defluoroalkylation of linear 1-(trifluoromethyl)alkenes through C-F activation to synthesize various gem-difluoroalkenes as carbonyl mimics. For the first time, arylboronate-activated alkyl Grignard reagents were uncovered in this cross-coupling reaction. Mechanistic studies confirmed that the tetraorganoborate complexes generated in situ were the key reactive species for this transformation.

Enantioselective Hydrogen Atom Transfer: Discovery of Catalytic Promiscuity in Flavin-Dependent 'Ene'-Reductases

Flavin has long been known to function as a single electron reductant in biological settings, but this reactivity has rarely been observed with flavoproteins used in organic synthesis. Here we describe the discovery of an enantioselective radical dehalogenation pathway for α-bromoesters using flavin-dependent 'ene'-reductases. Mechanistic experiments support the role of flavin hydroquinone as a single electron reductant, flavin semiquinone as the hydrogen atom source, and the enzyme as the source of chirality.

Stereoselective Ketone Rearrangements with Hypervalent Iodine Reagents

The first stereoselective version of an iodine(III)-mediated rearrangement of arylketones in the presence of orthoesters is described. The reaction products, α-arylated esters, are very useful intermediates in the synthesis of bioactive compounds such as ibuprofen. With chiral lactic acid-based iodine(III) reagents product selectivities of up to 73 % ee have been achieved.

Cobalt-bisoxazoline-catalyzed asymmetric kumada cross-coupling of racemic α-bromo esters with aryl grignard reagents

The first cobalt-catalyzed asymmetric Kumada cross-coupling with high enantioselectivity has been developed. The reaction affords a unique strategy for the enantioselective arylation of α-bromo esters catalyzed by a cobalt-bisoxazoline complex. A variety of chiral α-arylalkanoic esters were prepared in excellent enantioselectivity and yield (up to 97% ee and 96% yield). The arylated products were transformed into α-arylcarboxylic acids and primary alcohols without erosion of ee. The new enantioenriched α-arylpropionic esters synthesized herein are potentially useful in the development of nonsteroidal anti-inflammatory drugs. This method was conducted on gram-scale and applied to the synthesis of highly enantioenriched (S)-fenoprofen and (S)-ar-turmerone.

Enantioselective hydrogenation of α-substituted acrylic acids catalyzed by iridium complexes with chiral spiro aminophosphine ligands

Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids (see scheme). The complexes were highly active catalysts, showing turnover frequencies of up to 6000 h-1, and catalyst loadings could be reduced to 0.01 mol %. Copyright

Kinetic resolution of (R,S)-pyrazolides containing substituents in the leaving pyrazole for increased lipase enantioselectivity

With hydrolysis of (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) via Candida antarctica lipase B (CALB) as the model system, (R,S)-pyrazolides containing a leaving 3-, 4- or 3,4-substituted-pyrazole moiety are selected as the best substrates for preparing various optically pure carboxylic acids containing an α-chiral center. Great improvements of enzyme activity for the (R)-enantiomers with excellent enantioselectivity (VR/VS > 100) are obtainable, if (R,S)-pyrazolides containing a leaving 3- or 3,4-substituted-pyrazole moiety are employed for the hydrolysis or alcoholysis by methanol in anhydrous MTBE. A detailed kinetic analysis for (R,S)-N-2-phenylpropionylpyrazoles indicates that a bulky 3-substituent such as 3-(3-bromophenyl) or 3-(2-pyridyl) in the leaving pyrazole moiety has profound effects on decreasing the nucleophilic attack and proton transfer of catalytic serine for the slow-reacting enantiomer in anhydrous MTBE, as well as that and substrate affinity for both enantiomers in water-saturated MTBE. The resolution platform is also successfully applied to the hydrolysis of (R,S)-pyrazolides in water-saturated cyclohexane via Candida rugosa lipase (Lipase MY) having opposite enantioselectivity to CALB.

Highly enantioselective hydrogenation of α-aryl-β-substituted acrylic acids catalyzed by Ir-SpinPHOX

The enantioselective hydrogenation of a series of challenging substrates, α-aryl-β-substituted acrylic acids, was realized with high efficiency and enantioselectivity (up to 96%) under the catalysis of Ir(i) complex of Spiro-based P,N ligand, SpinPHOX.

Asymmetric esterification of ketenes catalyzed by an N-heterocyclic carbene

The chiral N-heterocyclic carbene precursor 2, derived from L-pyroglutamic acid, was found to be an efficient precatalyst for the enantioselective esterification of alkylarylketenes with benzhydrol to give the corresponding esters in good yields with good to high enantioselectivities (up to 95% ee).