Iminium salts synthesis

The reaction of enamines with iminium salts provides an alternative route to Mannich bases which are an attractive class of compounds, since they have found many applications (synthesis of drugs, pesticides, synthetic building blocks, etc.). This methodology has several basic advantages compared to the classic aminomethylation procedure15-18-24 ... 

The Bischler-Napieralski reaction is one of the traditional methods for isoquinoline synthesis, and has been applied to the preparation of fused quinolizidine systems. One simple example is the transformation of compound 246 into a 9 1 mixture of diastereomers 247 and 248 by treatment with phosphorus oxychloride followed by sodium borohydride reduction of a nonisolated iminium salt resulting from the cyclization (Scheme 49) <2000BMC2113>. 

The excellent reducing properties of potassium tetracarbonylhydrido-ferrate have been used to good effect in providing an efficient general piperidine synthesis from alkyl and aryl amines and glutaraldehyde210 (Scheme 138). The reaction probably proceeds via reduction of intermediate Schiff bases and cyclization via the iminium salt. 

Our own research group [11] has been interested in using vinylogous iminium salt derivatives for the preparation of highly functionalized pyrroles, thereby providing another alternative to the synthesis of lukianol A. 

Besides the allylation reactions, imines can also undergo enol silyl ether addition as with carbonyl compounds. Carbon-carbon bond formation involving the addition of resonance-stabilized nucleophiles such as enols and enolates or enol ethers to iminium salt or imine can be referred to as a Mannich reaction, and this is one of the most important classes of reactions in organic synthesis.104... 

After its isolation, the structure of alkaloid deplancheine (7) was unambiguously proved by several total syntheses. In one of the first approaches (14), 1,4-dihydropyridine derivative 161, obtained by sodium dithionite reduction of A-[2-(indol-3-yl)ethyl]pyridinium salt 160, was cyclized in acidic medium to yield quinolizidine derivative 162. Upon refluxing 162 with hydrochloric acid, hydrolysis and decarboxylation took place. In the final step of the synthesis, the conjugated iminium salt 163 was selectively reduced to racemic deplancheine. 

Recently, Malpass et al. reported a synthesis of epibatidine isomers also under reductive Heck conditions [134, 135]. 2-Azabicyclo[2.2.1]heptene 167 was assembled by cycloaddition of an iminium salt with cyclopentadiene. Treatment of 167 with 2-chloro-5-iodopyridine provided a mixture of exo-5-(6-chloro-3-pyridyl) derivative 168 and exo-6-(6-chloro-3-pyridyl) derivative 169. 

The same authors also published the synthesis of two nucleosides 135 and 136 by application of this process <20030L2067>. In these cases, the reagent iminium salts were generated in situ by adding the appropriate sugar and ammonium chloride to the reaction mixture which allowed the intermediate ring closure of the cyclic carbohydrate to an open-chained iminium salt. 

Two new syntheses to fused isoxazoles are worth mentioning. In a study for the synthesis of various related fused [l,3,5]triazinium salts, Okide described <1994JHC535> the conversion of 3-amino-5-methylisoxazole 223 with the iminium salt 224. The quaternary perchlorate salt 225 was obtained in medium yield (44%). A Russian research group <2004KGS592> reported that the isoxazole derivative 226 undergoes thermal cyclization when heated in xylene at higher temperature for an extended time, and the cyclized product 227 can be obtained in 53% yield. 

The iminium salt photoaddition reaction has been applied to the synthesis of N-heterocyclic systems (equation 70)126,127. 

Total synthesis of the representative protoberberines, (+)-xylopinine 151 (equation 71) and (+)-stylopine 152 (equation 72), have been achieved using silylarene-iminium salt photochemistry128. The photochemical routes appear to be superior to alternative ground-state methods involving dipolar cyclizations. 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

In 1976, the synthesis of oxaziridininm salt 66 was reported by Lusinchi and coworkers (Fig. 23) [128-130]. Salt 66 was obtained by either methylation of the corresponding oxaziridine with FSO Me or oxidation of the corresponding iminium salt with peracid. Subsequently, Hanquet and coworkers prepared oxaziridininm salt 67 by methylation of the corresponding oxaziridine with Meerwein s salt (MejO BF ") or oxidation of the A -methyl isoquinoUnium fluoroborate salt with peracid [131, 132],... 

Synthesis of antx-a has been done through a ring expansion of cocaine (20), from 1, 5-cyclooctadiene (21) and by intramolecular cyclization between an iminium salt and a nucleophilic carbon atom (22). The structure of antx-a is given in Fig. 1. 

The synthesis of iminium salt 85 by soda-lime pyrolysis through an intermediate enamine (83CJC2016) is inferior to that of salt 60 (Scheme 16). Cathodic cyclization of l-(E-oxoalkyl)pyridinium salts gives dia-stereomeric hydroxy compounds 86 and 87 in yields of 14-16% each (95AGE2007). 

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