Imines catalytic hydrogenation

What is more interesting is that no one to date has utilized a stereoselective imine catalytic hydrogenation strategy to make (5)-dapoxetine directly according to a four-step reaction sequence such as the one proposed in the following. 

A class of nitrogen-containing compounds that was omitted from the section just discussed includes imines and their- derivatives. Irnines are formed by the reaction of aldehydes and ketones with ammonia. Imines can be reduced to primary amines by catalytic hydrogenation. 

A somewhat more complex application of this notion is represented by the CNS stimulant fencamfine (83). Diels-Alder addition of cyclopentadiene and nitrostyrene affords the norbomene derivative, 80. Catalytic hydrogenation reduces both the remaining double bond and the nitro group (81). ° Condensation with acetaldehyde gives the corresponding imine (82) a second reduction step completes the synthesis of fencamfine (83). ... 

Catalytic hydrogenation of nitriles may result in several products primary, secondary, and tertiary amines imines hydrocarbons aldehydes amides and... 

The catalytic hydrogenation of the C=N bond of imines has attracted considerable attention, and a useful review covering the literature until 1996 has been reported by James.110 Chiral [Pg.91]

Scheme 8.4. Catalytic hydrogenation of imines using cationic iridium catalysts with the C02-philic BARF anion...

Samec and Backvall found that the dinuclear Shvo complex catalyzes the transfer hydrogenation of imines using benzene as solvent and isopropanol as the hydrogen source (Eq. (45)) [76]. These catalytic hydrogenations were typically carried out at 70 °C, and gave >90% yields of the amine in 4 h or less. 

The TEAF system can be used to reduce ketones, certain alkenes and imines. With regard to the latter substrate, during our studies it was realized that 5 2 TEAF in some solvents was sufficiently acidic to protonate the imine (p K, ca. 6 in water). Iminium salts are much more reactive than imines due to inductive effects (cf. the Stacker reaction), and it was thus considered likely that an iminium salt was being reduced to an ammonium salt [54]. This explains why imines are not reduced in the IPA system which is neutral, and not acidic. When an iminium salt was pre-prepared by mixing equal amounts of an imine and acid, and used in the IPA system, the iminium was reduced, albeit with lower rate and moderate enantioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Nevertheless, as other kinetic studies have indicated a pre-equilibrium with imine, it is possible that the proton formally sits on the catalyst and the iminium is formed during the catalytic cycle. It is, of course, possible that the mechanism of imine transfer hydrogenation is different to that of ketone reduction, and a metal-coordinated imine may be involved [55]. 

Dehydrogenation of Imines and Alcohols by Shvo Complexes 191 Catalytic Hydrogenations with Metal-Ligand Bifunctional Catalysis 193... 

Ti-F bond and generate a Ti-H species when 99 was treated with phenylsilane. The chirality transfer may take place through imine insertion into the Ti-H bond, similar to that in the catalytic hydrogenation process.1000 The reaction can be carried out by the subsequent addition of imines. The corresponding silylated amines can be obtained and further converted to enantiomerically enriched amines upon acid treatment. For example, in the presence of 99, N-methylimine 100 undergoes complete hydrosilylation within 12 hours at room temperature, with 97% ee and up to 5000 turnovers.103... 

Scheme 6.18. Three-component Zr-catalyzed asymmetric alkylation of imines by alkylzincs leads to the formation of optically enriched amines not accessible by alternative methods such as catalytic hydrogenation.

Several l,2,3,4-tetrahydronaphthalen-l,4-imines have been prepared by catalytic hydrogenation, e.g., 2 124. Compound 109 was... 

Asymmetric catalytic hydrogenation is unquestionably one of the most significant transformations for academic and industrial-scale synthesis. The development of tunable chiral phosphorous ligands, and of their ability to control enantioselectivity and reactivity, has allowed asymmetric catalytic hydrogenation to become a reaction of unparalleled versatility and synthetic utility. This is exemplified in the ability to prepare en-antiomerically enriched intermediates from prochiral olefins, ketones, and imines through asymmetric hydrogenation, which has been exploited in industry for the synthesis of enantiomerically enriched drugs and fine chemicals. 

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