Imine reduction mechanism

Kejrwords Dynamic kinetic asymmetric transformation (DYKAT) Dynamic kinetic resolution (DKR) Hydrogenation Imine reduction Ketone reduction Mechanism of carbonyl reduction Mechanism of imine reduction Mechanism of dUiydrogen activation Ruthenium catalysis Shvo s catalyst Transfer hydrogenation... 

Reduction of nitrostyrene with aqueous TiCl3 gives a 3,4-diarypyrrole directly in moderate yield (Eq. 10.46).52 The reaction proceeds via dimerization of anion radicals of nitrostyrene and reduction of the nitro function in the dimer to imines. Reduction of dinitrile with diisobutylalu-minum hydride (DIBAL) gives a-free pyrroles (Eq. 10.47) 53 both reactions may proceed in a similar mechanism. These pyrroles are useful intermediates for functionalized porphyrins. 

The Shvo diruthenium catalyst 13 (Fig. 34) has been used in non-asymmetric ketone and imine reduction, and the mechanism has been studied and reported in some detail [5, 111-115]. Catalyst 13 is also able to racemize amines [116], which allows it to be combined in a DKR process with an enzyme to create enantiomerically enriched amides. 

In 1999, Doye disclosed that dimethyltitanocene is a catalyst widely applicable to intermolecular hydroamination of alkynes with primary aryl- and alkylamines [302]. In the case of unsymmetrically substituted alkynes, the reaction occurs with high re-gioselectivity, forming the anti-Markovnikov products exclusively (Scheme 14.127). Kinetic studies suggest that the reaction mechanism involves the formation of a Ti-imido complex as the catalytically active species. Doye further developed a tandem Ti-catalyzed protocol of alkyne hydroamination and imine reduction, affording secondary amines in a fully catalytic one-pot reaction [303]. 

Ujaque and Lledos carried out a more comprehensive theoretical analysis on various mechanisms for reductions by 2 [64, 65]. An inner-sphere mechanism involving initial CO dissociation was readily eliminated based on a computed CO dissociation energy of 46 kcal mol . The energy barrier for the outer-sphere reduction of formaldehyde by 2 was computed as 8 kcal moP, while the lowest energy inner-sphere mechanism had a barrier of 35 kcal moP. The outer-sphere mechanism for imine reduction by 2 was shown to have a lower barrier (9 kcal moP ) than the best inner-sphere ring-slip mechanism ( 26 kcal moP ). 

Their proposed mechanism relies on a hexacoordinated silicon species obtained by a A7,A7-chelation of the activator and an arene-arene interaction between the latter and the substrate. The energy gain of this 7t-7t-stacking was calculated to be 6.3kcal mol and therefore crucial for the formation of the extracoordinate silicon species (Scheme 32.16). Without this hypervalent silicon, no reduction is observed. Thus, the application is limited to aromatic ketones and ketimines. More detailed information about imine reductions can be found in section 3 of this chapter. 

SCHEME 32.18. Mechanism of imine reduction with Hantzsch ester and a chiral Br0nsted acid. 

Active Figure 24.4 MECHANISM Mechanism of reductive amination of a ketone to yield an amine. Details of the imine-forming step were shown in Figure 19.8 on page 711. Sign in afwww.thomsonedu.com to see a simulation based on this figure and to take a short quiz. 

Scheme 2 Mechanism of the electrochemical or metal-promoted reductive coupling of imines in an acidic medium...

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied 686... 

Cyclization of 2-(l-alkynyl)XV-alkylidene anilines is catalyzed by palladium to give indoles (Equation (114)).471 Two mechanisms are proposed the regioselective insersion of an H-Pd-OAc species to the alkyne moiety (formation of a vinylpalladium species) followed by (i) carbopalladation of the imine moiety and /3-hydride elimination or (ii) oxidative addition to the imino C-H bond and reductive coupling. 

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]. 

The [lrCl(cod)]2-catalyzed reductive coupling of acrylates and imines provides trans-P-lactams with high diastereoselectivity (Equation 10.39) [67]. With regards to the reaction mechanism, in situ generated Ir-hydride reacts with acrylate 148 to produce an Ir enolate, which then reacts with the 147 to afford the P-amido ester 149. 

Asymmetric transfer hydrogenation of imines catalyzed by chiral arene-Ru complexes achieves high enantioselectivity (Figure 1.34). Formic acid in aprotic dipolar solvent should be used as a hydride source. The reaction proceeds through the metal-ligand bifunctional mechanism as shown in the carbonyl reduction (Figure 1.24). 

Kinetics and mechanisms of oxidation of amines by Ru porphyrin complexes (particularly TMP species) have been reviewed [42]. rranx-Ru(0)2(TMP)/02/ CgHg/50°C/24h oxidised primary and secondary amines in the oxidation of ben-zylamine frani-Ru(NHj)jCHjPh)2(TMP) was isolated and characterised crystallo-graphically. A mechanism involving a two-electron oxidation of benzylamine to A-benzylideneamine by tra i-Ru(0)2(TMP) was proposed with concomitant reduction of the latter to Ru (0)(TMP). This disproportionates to tranx-Ru "(0)2(TMP) and Ru"(TMP) the latter regenerates Ru" (0)(TMP) with O, while the second two-electron oxidation of the imine to the aldehyde is effected by tranx-Ru(0)2(TMP) [597], (Table 5.1) [598]. 

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