98611-98-4

Upstream product

• 563-80-4 3-methyl-butan-2-one 
• 100-46-9 benzylamine 
• 31776-80-4 3-methyl-1-phenyl-2-azapent-2-ene 
• 74-88-4 methyl iodide 
• 77390-49-9 (Z)-N-(1-Methylpropylidene)-1-phenyl-methanamine 

Downstream Products

• 144782-47-8 Benzyl-[2-methyl-1-((R)-toluene-4-sulfinylmethyl)-prop-(E)-ylidene]-amine 
• 110871-35-7 Benzyl-((R)-1,2-dimethyl-propyl)-amine 
• 163667-46-7 (R)-N-benzyl-3-methylbutan-2-amine 
• 144782-51-4 (1R,(S)R)-N-benzyl-1-isopropyl-2-(p-tolylsulfinyl)ethylamine 
• 40463-09-0 4-methyl-1-phenylpentan-3-one 

Relevant academic research and scientific papers

Modular Photocatalytic Synthesis of α-Trialkyl-α-Tertiary Amines

Molecules displaying an α-trialkyl-α-tertiary amine motif provide access to an important and versatile area of biologically relevant chemical space but are challenging to access through existing synthetic methods. Here, we report an operationally straightforward, multicomponent protocol for the synthesis of a range of functionally and structurally diverse α-trialkyl-α-tertiary amines, which makes use of three readily available components: dialkyl ketones, benzylamines, and alkenes. The strategy relies on the of use visible-light-mediated photocatalysis with readily available Ir(III) complexes to bring about single-electron reduction of an all-alkyl ketimine species to an α-amino radical intermediate; the α-amino radical undergoes Giese-type addition with a variety of alkenes to forge the α-trialkyl-α-tertiary amine center. The mechanism of this process is believed to proceed through an overall redox neutral pathway that involves photocatalytic redox-relay of the imine, generated from the starting amine-ketone condensation, through to an imine-derived product. This is possible because the presence of a benzylic amine component in the intermediate scaffold drives a 1,5-hydrogen atom transfer step after the Giese addition to form a stable benzylic α-amino radical, which is able to close the photocatalytic cycle. These studies detail the evolution of the reaction platform, an extensive investigation of the substrate scope, and preliminary investigation of some of the mechanistic features of this distinct photocatalytic process. We believe this transformation will provide convenient access to previously unexplored α-trialkyl-α-tertiary amine scaffolds that should be of considerable interest to practitioners of synthetic and medicinal chemistry in academic and industrial institutions.

Regioselective photochemical rearrangement of N-mesyloxylactams

N-Mesyloxylactams can undergo ring contraction either by C-3 (usually observed) or C-5 migration. C-5 migration can occur when the C-3 migration product possesses ring strain, but it does not usually compete with C-3 migration. The greater preference for C-3 migration is due to the carbonyl oxygen atom, which greatly stabilizes the intermediate. Studies of the photochemical rearrangement of N-mesyloxylactams showed that the lone pair of the carbonyl oxygen atom, and not the degree of the substitution atthe migrating carbon atoms, is the governing factor in the regioselectivity of the reaction. Copyright

Asymmetric hydrogenation of N-alkyl and N-aryl ketimines using chiral cationic Ru(diamine) complexes as catalysts: The counteranion and solvent effects, and substrate scope

Asymmetric hydrogenation of N-alkyl and N-aryl ketimines catalyzed by chiral cationic η6-arene-(N-monosulfonylated diamine) Ru(II) complexes has been investigated. Strong counteranion and solvent effects on the enantioselectivity were observed. The ruthenium catalyst bearing non-coordinating BArF- anion was found to be particularly effective for the hydrogenation of acyclic and exocyclic N-alkyl ketimines in the presence of (Boc)2O in dichloromethane or even under solvent-free conditions, providing chiral amines with up to >99% ee and full conversions. Alternatively, the ruthenium catalyst bearing achiral phosphate anion together with corresponding phosphoric acid as the additive was also efficient for the hydrogenation of N-alkyl ketimines in the absence of (Boc)2O with excellent enantioselectivities and full conversions. For N-aryl ketimines lower enantiomeric excesses were observed by using the ruthenium catalyst bearing BArF- anion. This catalytic protocol thus provides a facile and practical access to optically active amines and has been successfully employed in the gram-scale synthesis of enantiomerically pure (+)-sertraline.

Enantioselective hydrogenation of imines with chiral (phosphanodihydrooxazole)iridium catalysts

Cationic iridium(I) complexes of chiral phosphanodihydrooxazoles were used as catalysts for the enantioselective hydrogenation of prochiral N-alkyl and N-aryl imines. The complexes are air-stable crystalline solids that can be readily prepared and are easy to handle. The structures of two complexes were determined by X-ray analysis. For N-alkyl imines of acetophenone, enantiomeric excesses of up to 79% were obtained. Dialkyl ketimines and cyclic imines showed lower reactivity and selectivity. A remarkable dilution effect was observed for the hydrogenation of the N-phenyl imine of acetophenone: decreasing the substrate and catalyst concentration led to a significant improvement of the enantioselectivity. Thus, up to 89% ee could be achieved using 0.1 mol% of catalyst. The highest enantioselectivities were obtained in weakly coordinating solvents such as CH2C12. Additives such as halides, imides, or amines were found to poison the catalyst. Hydrogen pressures of 100 bar were usually employed, but in some cases identical results were achieved with only 1 bar H2.

Catalytic asymmetric hydrogenation of imines with a chiral titanocene catalyst: Scope and limitations

The asymmetric hydrogenation of imines with a chiral titanocene catalyst derived from Brintzinger's ansatitanocene complex 1 proceeds to afford amines with good to excellent enantioselectivity. The catalyst is particularly effective for the reduction of cyclic imines. For these substrates enantiomeric excesses from 95 to 99% were achieved. For acyclic imines lower enantiomeric excesses were observed. The reason for this is likely due to the fact that the acyclic imines are mixtures of anti and syn isomers which interconvert during the reaction. The catalyst was found to be tolerant of many functional groups found in organic synthesis. Thus the reaction represents an effective method for the synthesis of chiral cyclic amines.

α-Benzylation of Ketones by Reaction with Benzylamine. Regioselective Reduction of C-C Double Bonds in Cohjugated Enones

Prolonged reaction of some ketones with benzylamine at reflux converts them into α-benzyl derivatives by a route involving Aldol condensation of the related ketimine with benzaldimine followed by exclusive reduction of the resultant C-C double bond.Reduction does not occur when pure benzylamine is used under oxygen-free nitrogen, however the inclusion of a trace of benzaldehyde restores the efficiency of the reaction.Treatment of several ketones in this manner established the scope of the process.When the reaction was extended to the reduction of α,β-unsaturated enones again using benzylamine, reaction times were shorter and the product yield greater.The possibility that the reductive step was an intramolecular 1,5-hydrogen transfer was studied.

Formation and Isomerization of 2-Azaallyllithium Reagents in Deprotonations of N-Benzyl Ketimines Containing α-Protons

Deprotonation of the N-benzylimine of 3-pentanone by lithium diisopropylamide (LDA) in tetrahydrofuran occurs at the benzylic position to give a 2-azaallyllithium reagent in high yield.On standing, the 2-azaallyllithium reagent isomerizes to a 1-azaallyllithium reagent.The N-benzylimine of 2-butanone can be similarly deprotonated by LDA at the benzylic position in competition with deprotonation at the α-positions to give a 2-azaallyllithium reagent in up to 22percent yield.The N-benzylimine of acetone is not appreciably deprotonated at the benzylic position by LDA.Kinetic studies of the isomerization of 2-azaallyl- to 1-azaallyllithium reagent from the 3-pentanone imine suggest that this reaction proceeds by a protonation-deprotonation sequence.

Factors Controlling Regioselectivity in Deprotonations of Unsymmetrical Ketimines

The regioselectivity of deprotonation of equilibrium E-Z mixtures of the benzyl, n-butyl, cyclohexyl, phenyl, and tert-butyl imines of 2-butanone by lithium diisopropylamide (LDA) in tetrahydrofuran has been shown to be a function of both the nitrogen substituent and the temperature of the deprotonation reaction.High regioselectivity at either the methyl or methylene substituent could be obtained for all imines except the benzyl and n-butyl imines.Pure (Z)-2-butanone imines (R = n-C4H9, c-C6H11, t-C4H9), prepared by LDA deprotonation of acetone imines followed by methylation, were deprotonated by LDA at the methyl position at -78 deg C and at 0 deg C.Studies of the rates of deprotonation of the E and Z isomers of n-butyl, cyclohexyl, and tert-butyl imines of 2-butanone and of the rates and mechanisms of isomerizations of these isomeric ketimines were performed.Temperature dependent deprotonation regioselectivity was also observed in lithium diethylamide deprotonations of the benzyl, cyclohexyl, phenyl, and tert-butyl imines of 2-butanone.A general scheme accounting for these results and other accounts of variable regioselectivity in ketimine deprotonation is presented.