16725-75-0

Usage

Chemical compound

1-Butanone, 2-methyl-1-phenyl-, (R)-

Class

Phenethylamine

Use

Psychostimulant medication

Treatment for

Attention deficit hyperactivity disorder (ADHD) and narcolepsy

Mechanism of action

Increases dopamine and norepinephrine levels in the brain

Effects

Improves focus, attention, and impulse control

Potential for abuse

High

Dependence risk

High

Legal classification

Schedule II controlled substance in the United States

Upstream product

• 78-76-2 (S)-2-bromobutane 
• 53178-41-9 2-lithio-2-phenyl-1,3-dithiane 
• 4885-02-3 Dichloromethyl methyl ether 
• 109529-28-4 (-1-methylpropyl)(phenyl)(3-(trimethylsiloxy)propoxy)borane 
• 77858-01-6 ((S)-1-Methoxymethyl-2-phenyl-ethyl)-[1-phenyl-but-(E)-ylidene]-amine 
• 74-88-4 methyl iodide 
• 100-58-3 phenylmagnesium bromide 
• 108509-71-3 (R)-1-((1S,5R,7R)-10,10-Dimethyl-3,3-dioxo-3λ⁶-thia-4-aza-tricyclo[5.2.1.0^1,5]dec-4-yl)-2-methyl-butan-1-one 
• 609815-86-3 Trimethyl-((Z)-2-methyl-1-phenyl-but-1-enyloxy)-silane 
• 71-43-2 benzene 
• 32231-50-8 (R)-2-methylbutyric acid 
• 91739-22-9 (2′S)-2-Methoxymethyl-1-((2R)-2-methyl-1-phenylbutylidenamino)pyrrolidine 
• 100-47-0 benzonitrile 
• 177914-33-9 C₁₇H₁₉NOS 

Downstream Products

• 16725-77-2 (1R,2R)-2-methyl-1-phenylbutan-1-ol 
• 16725-79-4 (1S,2R)-2-methyl-1-phenylbutan-1-ol 
• 938-87-4 2-methyl-1-phenyl-butan-1-one 
• 873998-30-2 2-bromo-2-methyl-1-phenylbutan-1-one 

Relevant academic research and scientific papers

Stereocontrol in Preparation of Cyclopalladated Alkylaromatic Oximes and Evaluation of Their Stereoselective Esterase-Type Catalytic Activity

The stereochemistry of 2′-methylbutyrophenone oxime, the rates of ortho-palladation of its E- and Z-isomers, and catalytic activity of the respective Pd complexes were studied. The full stereoisomeric composition of oximes was established for the first time by means of supercritical fluid chromatography on chiral polysaccharide column. It was shown that enantiomeric excesses of both E/Z-isomers of (S)-2′-methylbutyrophenone oxime (1S) and (R)-2′-methylbutyrophenone oxime (1R) were equal to 92 ± 2. The cyclopalladation study revealed that while E-isomer is ortho-palladated very quickly its Z-counterpart does not enter this reaction. However, upon coordination to Pd(II), Z-oxime slowly isomerizes into E-form with fast subsequent cyclopalladation, so it was possible to perform ortho-palladation of E-oxime in kinetic resolution mode with removal of unreacted Z-oxime. Comparatively rare cis-structure of cyclopalladated oxime dimer was proved by means of single-crystal X-ray study. For the first time, it was shown that ortho-palladated chiral oximes behave as enantioselective catalyst in the hydrolysis of chiral esters.

Rearrangement of N- tert-Butanesulfinyl Enamines for Synthesis of Enantioenriched α-Hydroxy Ketone Derivatives

Treating chiral N-tert-butanesulfinyl ketimines with potassium hexamethyldisilazide (or potassium tert-butoxide) and methyl triflate gives N-methylated N-tert-butanesulfinyl enamine intermediates that undergo stereoselective [2,3]-rearrangement to afford α-sulfenyloxy ketones with excellent enantiopurities. This cascade of enamination-N-methylation-rearrangement was even used to generate acyclic tertiary α-hydroxy ketones bearing two α-substituents showing negligible differences in bulkiness, such as methyl and ethyl groups.

Fluoride Anions in Self-Assembled Chiral Cage for the Enantioselective Protonation of Silyl Enol Ethers

The potential of Song's chiral oligoethylene glycols (oligoEGs) as catalysts was explored in the enantioselective protonation of trimethylsilyl enol ethers in combination with alkali metal fluoride (KF and CsF) and in the presence of a proton source. Highly enantioselective protonations of various silyl enol ethers of α-substituted tetralones were achieved, producing chiral α-substituted tetralones in full conversion and with up to 99% ee. The established protocol was successfully extended to the synthesis of biologically relevant chiral α-substituted chromanone and thiochromanone derivatives.

Chiral bronsted acid from a cationic gold(I) complex: Catalytic enantioselective protonation of silyl enol ethers of ketones

A chiral Bronsted acid has been developed from a cationic gold(I) disphosphine complex in the presence of alcoholic solvent and applied to the enantioselective protonation reaction of silyl enol ethers of ketones. Various optically active cyclic ketones were obtained in excellent yields and high enantioselectivities, including cyclic ketones bearing aliphatic substrates at the α-position. Furthermore, the application of this Bronsted acid was extended to the first Bronsted acid-catalyzed enantioselective protonation reaction of silyl enol ethers of acyclic substrates, regardless of their E/Z ratio.

Non-destructive Removal of the Bornanesultam Auxiliary in α-Substituted N-Acylbornane-10,2-sultams under Mild Conditions: An Efficient Synthesis of Enantiomerically Pure Ketones and Aldehydes

α-Substituted N-acylbornane-10,2-sultams 6, 9, and 10 can be converted into enantiomerically pure ketones 5, 13, and 14, respectively, via a two-step procedure involving a known mercaptolysis reaction followed by an -mediated coupling of the resulting S-benzyl thioesters with Grignard reagents.Furthermore, enantiomerically pure aldehydes 23 can be obtained from α-substituted N-acylbornane-10,2-sultams 6 via a one-step reduction with (i-Bu)2AlH.No epimerization at the α-chiral center is observed during the cleavage reaction whereby the chiral auxiliary, bornane-10,2-sultam 1 or ent-1, was recovered.By using this methodology, several natural products or precursors thereof can be prepared.

Regio- and enantioselective substitution of acyclic allylic sulfoximines with butylcopper in the presence of lithium iodide and boron trifluoride

Enantiomerically pure N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(phenyl)cinnamylsulfoximmes as well as the corresponding crotylsulfoximines have been prepared from N-methyl-, N-benzyl-, and N-(methoxyethyl)-S-(lithiomethyl)sulfoximines and carbonyl com

ASYMMETRIC SYNTHESES VIA METALATED CHIRAL HYDRAZONESOVERALL ENANTIOSELECTIVE α-ALKYLATION OF ACYCLIC KETONES

A general method is described, which allows the overall enantioselective α-alkylation of acyclic ketones in good overall yields (44-86percent, 4 steps) and enantioselectivities ranging routinely from >94percent ee up to virtually complete asymmetric induction (99.5percent ee).The acyclic ketones are transformed to their corresponding "SAMP-hydrazones" (S)-2 by reaction with the enantiomerically pure hydrazine (S)-1-amino-2-methoxymethyl-pyrrolidine , readily available from (S)-proline.Metalation to form chiral azaenolates (S)-3 of ECCZCN-configuration and then alkylation to product hydrazones 4, followed by hydrazone cleavage via acidic hydrolysis of methiodides 9 in a two phase system or ozonolysis, leads to α-substituted, enantiomerically enriched, acyclic ketones 5.In special cases, where a phenyl group is directly attached to the newly generated center of chirality (5n,o,p), only low enantiomeric excesses are observed. 17 Examples, including first applications in natural product synthesis (cf 5a,b,e, and h) are summarized.

Asymmetric Induction in the Reduction of Optically Active N-Alkylidenesulphinamides by Metal Hydrides. A New, Efficient Enantioselective Route to Chiral Amines

A series of racemic and optically active N-alkylidenesulphinamides has been prepared and their reduction by metal hydrides studied.The extent of asymmetric synthesis mainly depends on the nature of the reducing species; the best results (up to 92percent of stereoselectivity) are obtained with alkoxy-lithium aluminium hydrides.A new, highly enantioselective synthesis of amines is described.

An Asymmetric Synthesis of Acyclic and Macrocyclic α-Alkyl Ketones. The Role of (E)- and (Z)-Lithioenamines

Metalation and alkylation of chiral imines derived from C10, C12, and C15 cyclic ketones gave, under kinetic metalation conditions, 2-alkylcycloalkanones of absolute configuration opposite to that formed from thermodynamic metalation.Thus, (S)-(-)-2-methylcyclododecanone is formed kinetically in 60percent ee, whereas (R)-(+)-methylcyclododecanone is reached in 80percent ee under thermodynamic conditions.In a similar fashion, acyclic ketones 20, via their chiral imines 17, are alkylated enantioselectively under both kinetic and thermodynamic modes.The kinetic metalation gives exclusively the (Z)-lithioenamines (19), while reflux of this lithio anion gives only the (E)-lithioenamine (19).Chiral α-substituted ketones are produced in 18-97percent ee.

Enolisation baso-catalysee des cetones : 2e partie : Racemisation de methyl-2 phenyl-1 butanones-1 substituees en milieux fortement basiques

The base-catalyzed enolization of a ketone transforms the latter into an enolate ion via an activated complex in which a proton α to the carbonyl is transferred between its original site and the base catalyst.The position of the proton in the activated complex along the reaction pathway between the substrate and the base depends on the basic strengths of these entities.Some authors have suggested a regular variation of the position of the proton with the basicity of the medium, which led us to further investigate this question.We chose to use the Hammett correlation.As a matter of fact, Hammett's slope ρ correlates with the charge density on the substrate in the activated complex, therefore it was reasonable to think that the ρ values would be a function of the distance between the proton and the substrate.The experimental part of this work consists of the determination of enolization rates of substituted aromatic ketones in media of various basicities, in order to plot the correlation log10 k = (?).For practical reasons, we chose to study the racemization rates of five optically active substituted 2-methyl-1-phenyl-butan-1-ones.These ketones were synthesized by Friedel-Crafts reactions, which explains the fact that the substituents on the aromatic ring are essentially electrodonating : p-OCH3, 3',4'-dimethyl, p-CH3, H, p-Cl.The reaction media used are, by increasing basicities : water-dioxane 64/36 v/v + OH-, water-ethanol 1/2 + OH-/C2H5O-, ethanol + C2H5O-, ethanol-DMSO 2/1, 1/1 and 1/2 + C2H5O-, ethanol-HMPA 1/2 + C2H5O-.The ρ values in these solvents are respectively : 1.1, 2.0, 2.1, 2.2, 2.3, 2.4, 2.1.They are all positive.One finds that : 1. in strongly aqueous media, water-dioxane 64/36 and water (see preceding paper), ρ values are close to + 1, whereas in the other (slightly or non aqueous) media, they are of about + 2.This can be due to the nature of the base (OH- in one case and C2H5O- in the other), to the amount of water in the solvent, or to the nature of the organic solvent.One can also contemplate, as some authors did, the possibility of a change in the reaction mechanism according to the nature of the base. 2. if we take into account the experimental error on ρ values, there is only little (if any) change in the latter with the alkalinity of the medium (H functions for the various solvents used vary approximately from 14 to 19, which corresponds to an appreciable alkalinity increase).The conclusion is that the substrate retains the same charge density in the activated complex, the geometry of which consequently is the same in all media.According to the slope of the straight line log10 kobs = (H), which is 0.41 the proton being transferred in the activated complex could be slightly closer to the substrate than to the attacking base.