Catalysts iminium salts

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]. 

In 1998, Page and coworkers reported a series of dihydroisoquinoline-related iminium salts which can be readily synthesized in three steps from a chiral amine (Scheme 14) [140-143], Among the catalysts tested for asymmetric epoxidation, iminium salts 74 were found to be efficient catalysts (Fig. 24, Table 7, entries 2, 4-6, 17-19). Iminium salts 74a can epoxidize 4-phenyl-1,2-dihydronaphthalene in up to 63% ee (Table 7, entry 17). 

In 1996, Aggarwal and coworkers synthesized binaphthyl-based iminium salt 76 via oxidation and methylation from binaphthylamine (Scheme 15) [147], Catalyst loading of 5 mol% is sufficient to catalyze the epoxidation of a number of olefins in good yield. Up to 71% ee can be obtained for 1-phenylcyclohexene oxide using this catalytic system (Table 7, entry 8). 

In 2001, Yang and coworkers studied the use of in situ generated acyclic iminium salts as epoxidation catalysts [159]. Epoxidations of a number of aUcenes proceed with 20-50 mol% of amine 85 and aldehyde 86 with Oxone as the primary oxidant (Fig. 28.) Methylstilbene can be obtained in 100% conversion and 59% ee. 

The epoxidation of olefins catalyzed by iminium salts and amines (or ammonium salts) is emerging as a new technique for the functionalization of simple aUcenes. These catalysts have relatively simple structures and hence are easily produced at scale they offer potential as green oxidation catalysts. These organic salts are effective oxygen transfer reagents towards electron-rich unfunctionalized olefins. For the iminium salt systems oxone oxidizes an iminium salt to the oxaziridi-nium intermediate, which then transfers oxygen to the olefin and as oxone reacts readily with iminium ions to regenerate the oxaziridinium species catalyti-cally, efficient oxidation is possible. 

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. 

Figure 1.49 Amines and iminium salt epoxidation catalysts.

A cyclic iminium salt was hydrogenated using an Ir catalyst with (S)-(3,5-fBu)-tLANOP, an amidophosphinephosphinite ligand, in the presence of (n-C4H9)4NI under 100 atm of H2 to give the S ammonium salt in 86% ee and in 46% yield, accompanied by 54% of the decahydroisoquinoline derivative (Scheme 10) [23]. 

Another interesting example was reported by Yamaguchi et al. by using a simple L-proline rubidium salt 27 (Scheme 8D. 15) [32], A reversible iminium salt formation, involving the amine moiety of the catalyst and the carbonyl group of an enone, was proposed as the key intermediate. 

Homologous biphenyl and binaphthyl tertiary azepines (4) and quaternary iminium salts, prepared from (+)-(5,5 )-L-acetonamine, behave as effective catalysts for the enantioselective epoxidation of unfunctionalized alkenes with Oxone (ee up to 83%).113... 

Both chiral ketones and chiral iminium salts have proven their potential as metal-free enantioselective catalysts of epoxidation. The enantiomeric excesses currently observed with chiral ketones are higher than those achieved with iminium salts. In terms of practicability, the Shi ketone 10, an inexpensive and readily available... 

Tetraphenylphosphonium monoperoxysulfate can be prepared from Oxone and tetraphenyphosphonium chloride [57]. Synthesis of the iminium salt catalyst is described in the source paper (see [57]). 

Aggarwal and Wang have investigated binaphthyl-based iminium salt 62 (Figure 13) 5 mol% of the catalyst is sufficient to mediate the asymmetric epoxidation of phenylcyclohexene (80% yield, 71% ee), whereas the induction was not as efficient for methylcyclohexene (80% yield, 39% ee) <1996CC191>. 

Another useful variation is the Pictet-Spengler isoquinoline synthesis, also known as the Pictet-Spengler reaction. The reactive intermediate is an iminium ion 49 rather than an oxygen-stabilized cation, but attack at the electrophilic carbon of the C=N unit (see 16-31) leads to an isoquinoline derivative. When a p-aryla-mine reacts with an aldehyde, the product is an iminium salt, which cyclizes with an aromatic ring to complete the reaction and generate a tetrahydroisoquinoline." ° A variety of aldehydes can be used, and substitution on the aromatic ring leads to many derivatives. When the reaction is done in the presence of a chiral thiourea catalyst, good enantioselectivity was observed." ... 

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