852051-16-2

Upstream product

• 1205553-66-7 (S)-3-methyl-4-nitro-5-(3-nitro-2-phenylpropyl)isoxazole 
• 1001058-61-2 (S)-4-nitro-3-phenylbutanal 
• 14371-10-9 (E)-3-phenylpropenal 
• 5153-67-3 nitrostyrene 
• 252338-27-5 ethyl (S)-2-ethoxycarbonyl-4-nitro-3-phenylbutyrate 
• 104-55-2 3-phenyl-propenal 
• 363152-44-7 (S)-4-Nitro-3-phenyl-1-((1R,2R,4R)-1,7,7-trimethyl-2-trimethylsilanyloxy-bicyclo[2.2.1]hept-2-yl)-butan-1-one 
• 102-96-5 (2-nitroethenyl)benzene 
• 34687-03-1 4-nitro-3-phenylbutanoic acid methyl ester 
• 363152-46-9 (S)-1-((1R,2R,4R)-2-Hydroxy-1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-4-nitro-3-phenyl-butan-1-one 

Downstream Products

• 1078-21-3 (S)-Phenibut 
• 62624-45-7 (S)-4-phenyl-1-tosylpyrrolidin-2-one 

Relevant academic research and scientific papers

Metal-Free Deoxygenation of Chiral Nitroalkanes: An Easy Entry to α-Substituted Enantiomerically Enriched Nitriles

A metal-free, mild and chemodivergent transformation involving nitroalkanes has been developed. Under optimized reaction conditions, in the presence of trichlorosilane and a tertiary amine, aliphatic nitroalkanes were selectively converted into amines or nitriles. Furthermore, when chiral β-substituted nitro compounds were reacted, the stereochemical integrity of the stereocenter was maintained and α-functionalized nitriles were obtained with no loss of enantiomeric excess. The methodology was successfully applied to the synthesis of chiral β-cyano esters, α-aryl alkylnitriles, and TBS-protected cyanohydrins, including direct precursors of four active pharmaceutical ingredients (ibuprofen, tembamide, aegeline and denopamine).

Telescoped Continuous Flow Synthesis of Optically Active γ-Nitrobutyric Acids as Key Intermediates of Baclofen, Phenibut, and Fluorophenibut

The two-step flow asymmetric synthesis of chiral γ-nitrobutyric acids as key intermediates of the GABA analogues baclofen, phenibut, and fluorophenibut is reported on a multigram scale. The telescoped process comprises an enantioselective Michael-type add

Oxidative Amidation of Nitroalkanes with Amine Nucleophiles using Molecular Oxygen and Iodine

The formation of amides and peptides often necessitates powerful yet mild reagent systems. The reagents used, however, are often expensive and highly elaborate. New atom-economical and practical methods that achieve such goals are highly desirable. Ideally, the methods should start with substrates that are readily available in both chiral and non-chiral forms and utilize cheap reagents that are compatible with a wide variety of functional groups, steric encumberance, and epimerizable stereocenters. A direct oxidative method was developed to form amide and peptide bonds between amines and primary nitroalkanes simply by using I2 and K2CO3 under O2. Contrary to expectations, a 1:1 halogen-bonded complex forms between the iodonium source and the amine, which reacts with nitronates to form α-iodo nitroalkanes as precursors to the amides.

Chiral ionic liquids bearing O-silylated α,α-diphenyl (S)- Or (R)-prolinol units: Recoverable organocatalysts for asymmetric michael addition of nitroalkanes to α,β-enals

Chiral ionic liquids bearing O-silylated α,α-diphenyl (S)- or (R)-prolinol units tagged to the imidazolium cation were synthesized and their activity as catalysts in the Michael addition of nitroalkanes to α,β-unsaturated aldehydes was evaluated. Respective (S) or (R) adducts were obtained in the reactions in high yields (up to 95 %) and with high enantio-selectivity (up to 99% ee). Remarkably, the immobilized orgariocatalysts could be used five times without any decrease in product: yields or ee values. (R)-Michael adducts could be easily transformed into the most active (R) enantiomers of medications Phenibut, Baclofen, and Rolipram for the treatment of CNS disorders.

Catalytic asymmetric conjugate addition of nitroalkanes to 4-nitro5-styrylisoxazoles

(Chemical equation presented) Nitro versus nitro: 4-Nitro-5- styrylisoxazoles were used as masked α,β-unsaturated carboxylic acids in the titled catalytic asymmetric transformation. The 4-nitroisoxazole core acts as an activator of the conjugated alkene and a latent carboxylate functionality. The reaction proceeded with 5 mol% of a readily prepared phasetransfer catalyst at room temperature with remarkable diastereo- and enantioselectivity (see scheme).

A short and convenient chemoenzymatic synthesis of both enantiomers of 3-phenylGABA and 3-(4-chlorophenyl)GABA(Baclofen)

Both enantiomers of the pharmacologically active GABA analogues 4-amino-3-phenyl and 4-amino-3-(4-chlorophenyl)butyric acid (Baclofen) with high enantiomeric excesses were synthesized by a chemoenzymatic method involving α-chymotrypsin mediated kinetic resolutions of the corresponding 3-phenyl- and 3-(4-chlorophenyl)-4-nitrobutyric acid methyl ester precursors.

Diastereoselective Michael reactions of (1R)-(+)-camphor methyl ketone enolates with nitro olefins

The reaction of the sodium enolate of the methyl ketone 2 with a range of nitro olefins proceeds readily to give the corresponding Michael adducts in good yields and diastereoselectivities. Subsequent oxidative cleavage of the acyloin moiety provides γ-nitroalkanoic acids along with (1R)-(+)-camphor, the chiral auxiliary of the process, which can be recovered and reused.