Iminium salt mechanism

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

On the other hand, the known facts point to an alternative interpretation. The stereochemical course of the reaction may be explained in terms of a polar [2s + 2s] cycloaddition15 which is observed in reactions between very electron-poor and very electron-rich alkcnes. Namely, polar [2 + 2] cycloadditions usually proceed with high regioselectivity ( head to head ) and stereoselectivity under mild conditions33 35. This mechanism is also supported by the fact that a closely related reaction (between an ynamine and iminium salts) passes through a cyclic 4-membered intermediate36, which is probably the result of a polar [2 + 2] cycloaddition (see refs 10 and 37). 

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]. 

Goncalves et have compared the amine (V) and the iminium salt (W) for the enantioselective epoxidation of some prochiral olefins in acetonitrile/water and found that the yields and ees are nearly the same for the epoxidation of a selection of olefins. The amines of type (X) are less well developed. Armstrong has summarized the developments in this field and suggested mechanisms based on hydrogen bonded species, one of which is shown in Figure 1.49. Typical yield and ee data for the epoxidation of 1-phenylcyclohexene for these catalysts are also shown in Figure 1.49. 

Two mechanisms have been proposed for the Knoevenagel reaction. In one, the role of the amine is to form an imine or iminium salt (378) which subsequently reacts with the enolate of the active methylene compound. Under normal circumstances elimination of the amine would give the cinnamic acid derivative (379). However, when an o-hydroxy group is present in the aromatic aldehyde intramolecular ring closure to the coumarin can occur. The timing of the various steps may be different from that shown (Scheme 118). 

The reaction mechanism for A-oxidation by performic acid has been studied by AMI calculation methods.174 The iminium salt A-mcthyl-3,4-dihydroisoquinolinium p-toluenesulfonate has been used to catalyse the oxidation of the azo dye calmagite by peracetic acid. The mechanism at pH 10 involves peracid oxidation of the quinolinium ion to form an oxaziridinium salt, which then acts as an oxygen transfer agent for oxidation of cahnagite.175 The presence of lithium salts affects the course of the reaction determining the formation of benzoyl peroxide and benzoic acid as final products in the oxidation of benzaldehyde by perbenzoic acid.176,177... 

The NaBD4 reduction of sulfoxides of thiohemiaminals performed on 6-hydroxythiobinupharidine syn-sulfoxide (24), 6 -hydroxythiobinupharidine syn-sulfoxide (25), and 6,6 -dihydroxythiobinupharidine syn-sulfoxide (26) follows a single steric mode (90% of deuterium incorporation) and introduces axial deuterium at both C-6 and C-6. This reduction may not follow a mechanism with intermediate iminium salt formation (36). The presence of strong hydrogen bonding and the absence of a-iminium salts in the reacting mixture support this conclusion. 

The alkylated iminium salt hydrolyzes to the alkylated ketone. The mechanism of this hydrolysis is similar to the mechanism for acid-catalyzed hydrolysis of an imine (Section 18-15). 

Without looking back, propose a mechanism for the hydrolysis of this iminium salt to the alkylated ketone. The first step is attack by water, followed by loss of a proton to give a carbinolamine. Protonation on nitrogen allows pyrrolidine to leave, giving the protonated ketone. 

The cyclization of O-allyl oximes 1, performed with diphenyl diselenide/ammonium thiosulfate/ trifluorosulfonic acid or phenylselenenyl bromide, gave cyclic iminium salts 2 via an intramolecular antt -addition mechanism. By addition of water to the reaction mixture, 3-substi-tuted isoxazolidines 3 are formed in good yield. When the salts 2 were prepared by using phenylselenenyl bromide, A-alkyl 3-substituted isoxazolidines 4 were afforded in good yield by reduction of 2 with sodium borohydride in methanol247-249. 

The corresponding inter-and intra-raolecular additions of allyl-silanes to iminium salts give rise after desilylation to synthetically useful biradical intermediates. Evidence for the existence of two mechanisms for such reactions, differing only in the timing of carbon-silicon bond cleavage and carbon-carbon bond formation, has been described. Analogous electron transfer... 

Now the enol of acetyl CoA adds to the iminium salt to complete the skeleton of the piperidine alkaloids. Hydrolysis and decarboxylation by the usual cyclic mechanism (p. 678) gives pelletierine. 

The mechanism of the Petasis boronic acid-Mannich reaction is not fully understood. In the first step of the reaction, upon mixing the carbonyl and the amine components, three possible products can form iminium salt A, diamine B, and a-hydroxy amine C. It was shown that preformed iminium salts do not react with boronic acids. This observation suggests that the reaction does not go through intermediate A. Both intermediate B and C can promote the formation of the product. Most likely, the reaction proceeds through intermediate C, where the hydroxyl group attacks the electrophilic boron leading to an ate -complex. Subsequent vinyl transfer provides the allylic amine along with the boronic acid sideproduct. 

Li, Y., Xiao, H., Wu, J. The study on the mechanism of iminium salts as potential Mannich reagents. Part 2. Ethylene as pseudo-acid component. THEOCHEM A995, 333, 165-170. 

Li, Y. M., Xiao, H. M. Studies on the mechanism of Mannich reaction involving iminium salt as potential Mannich reagent. III. Furan as pseudo acid component, tnt. J. Quantum Chem. 1995, 54, 293-297. 

Morphinan derivative 58a, which was synthesized from naltrexone (1) [25, 66, 67], was dehydrated with SOCl2 in pyridine to afford the dehydrated product 60 and an abnormal rearrangement product 59 (iminium salt) (Scheme 25). The reaction mixture was separated by silica gel column chromatography with a CHCl /MeOH eluent to isolate pure iminium ion 59 in 28% yield, together with the dehydrated product 60 in 71% yield. In H NMR analysis, a vinyl proton of iminium chloride 59 was observed at 10.13 ppm this suggested that 59 was an iminium compound, not an ot-chloroamine. In contrast, when 4,5-epoxymorphinan 35 was subjected to the same reaction conditions, only the dehydrated product 61 was obtained (Scheme 25) [22]. We became interested in the abnormal stability of the iminium salt and attempted to improve its yield. A plausible mechanism for the rearrangement reaction that produced the iminium chloride 59 is shown in Scheme 26. 

Scheme 26 A plausible mechanism for the rearrangement of morphinan derivative 58a to produce the iminium salt 59...

Key Words Ethylene oxide, Propylene oxide. Epoxybutene, Market, Isoamylene oxide. Cyclohexene oxide. Styrene oxide, Norbornene oxide. Epichlorohydrin, Epoxy resins, Carbamazepine, Terpenes, Limonene, a-Pinene, Fatty acid epoxides, Allyl epoxides, Sharpless epoxidation. Turnover frequency, Space time yield. Hydrogen peroxide, Polyoxometallates, Phase-transfer reagents, Methyltrioxorhenium (MTO), Fluorinated acetone, Alkylmetaborate esters. Alumina, Iminium salts, Porphyrins, Jacobsen-Katsuki oxidation, Salen, Peroxoacetic acid, P450 BM-3, Escherichia coli, lodosylbenzene, Oxometallacycle, DFT, Lewis acid mechanism, Metalladioxolane, Mimoun complex, Sheldon complex, Michaelis-Menten, Schiff bases. Redox mechanism. Oxygen-rebound mechanism, Spiro structure. 2008 Elsevier B.V. 

P. C. B. Page, D. Barros, B. R. Bucklev, B. A. Marples, Organocatalysis of asymmetric epoxidation mediated by iminium salts Comments on the mechanism. Tetrahedron, Asymmetry 16 (2005) 3488. 

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