Of iminium salts

The reduction was studied in more detail by Cook and Schulz (52). They demonstrated conclusively that reduction of iminium salts by secondary amines is possible as illustrated in Eqs. (7) and (8). The oxidation... 

The alkylation of imines by an alkyl halide to give an iminium salt will be illustrated by selected reactions over a period of years. A more complete survey is available (88). Decker and Becker (89) prepared a number of iminium salts (91, for example) by mixing methyl iodide and aromatic imines in benzene. 2,5-Dimethyl-2-pyrroline (92) has been alkylated and the... 

For purposes of characterization of enamines the perchlorate salts are preferred, as they crystallize well, and the perchlorate anion has no tendency to add to the iminium cation. Other salts, including hexachlorostannates (13), hexachloroantimonates (13), chlorides, bromides, tetraphenylborates, and nitrates, have also been used. Recently a method for the preparation of iminium salts directly from aldehydes or ketones and the amine perchlorate has been reported (16). 

In most reviews of enamine chemistry the reactions of iminium salts are scattered throughout the review and are consequently not covered in a comprehensive manner. This chapter will be an attempt to look at reactions that, at one stage or another, proceed by nucleophilic addition to the iminium intermediate. The subject of enamines has been reviewed 1-4) and certain aspects of iminium salt chemistry such as reduction of aromatic quaternary salts have been treated in detail (5). Consequently, the reduction of aromatic quaternary salts with complex hydrides will be presented here only briefly. Although the literature (especially 1950-1967) has been checked with care, the author can make no claim to completeness. The... 

II. Structure, Preparation, and Detection of Iminium Salts A. Structure oe Iminium Salts The positively charged carbon-nitrogen double bond... 

The close agreement of the three methods supports the contention that protonation at low temperatures first occurs at nitrogen and is followed by a proton shift to give the iminium salt (M). The rate of this rearrangement is dependent on temperature, the nature of the amine, and the nature of the carbonyl compound from which the enamine was made. Even with this complication the availability of iminium salts is not impaired since the protonation reaction is usually carried out at higher temperatures than —70°. Structurally complicated enamines such as trichlorovinyl amine can be readily protonated (17,18). 

The alkylation of aldimines and ketimines as a method for obtaining iminium salts is now useful only for the preparation of iminium salts not accessible by any of the newer methods. The preparation of and 8 illustrates the conversion of ketimines to iminium salts (9,21). 

The presence of iminium salts can be detected by chemical means or by spectroscopic methods. The chemical means of detecting iminium salts are reactions with nucleophiles and are the subject of this review. The spectroscopic methods are more useful for rapid identification because with the large number of model compounds available now the spectroscopic methods are fast and reliable. The two methods that are used primarily are infrared and nuclear magnetic resonance spectroscopy. Some attempts have been made to determine the presence of iminium salts by ultraviolet spectroscopy, but these are not definitive as yet (14,25). 

Nuclear magnetic resonance has revolutionized structure determination of iminium salts. A compilation of various resonances for acyclic and cyclic iminium salts are given in Tables 3 and 4 for comparison purposes and for determination of trends. It should be noted that the simplest symmetrically... 

Reaction of Iminium Salts with Lithium Reagents... 

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. 

Reduction of iminium salts with diborane and by the Meerwein-Ponndorf method have been reported (89). 

Reduction of Iminium Salts with Complex Hydrides... 

A representative list of aziridinium salts prepared by reaction of iminium salts with diazomethane is given in Table 9. The reactions of aziridinium salts are many and varied, but will not be given here since their synthetic utility has been explored and reported elsewhere 109,112-114). The products from the reaction of iminium chlorides and diazomethane are reported in Table 10. Many more examples are available in the literature 16). 

The reaction of other nucleophiles such as amines 123,124), hydroxyl-amines, various carbanions, and hydroxide 120) have been tried but not examined in detail. Hydrolysis of iminium salts is covered elsewhere 123). 

The reaction of iminium salts such as 66 with salts of trichloroacetic acid has been shown to yield amides such as 84 on hydrolysis 126). It was suggested that the reaction proceeds by addition of dichlorocarbene to give an aziridinium intermediate (85), which was opened by trichloroacetate followed by hydrolysis to give the observed products 126). The observed products from the reaction can be accounted for by formation of CCI3,... 

The previous sections have dealt with stable C=N-I- functionality in aromatic rings as simple salts. Another class of iminium salt reactions can be found where the iminium salt is only an intermediate. The purpose of this section is to point out these reactions even though they do not show any striking differences in their reactivity from stable iminium salts. Such intermediates arise from a-chloroamines (133-135), isomerization of oxazolidines (136), reduction of a-aminoketones by the Clemmensen method (137-139), reductive alkylation by the Leuckart-Wallach (140-141) or Clarke-Eschweiler reaction (142), mercuric acetate oxidation of amines (46,93), and in reactions such as ketene with enamines (143). 

Reactions at the carbon-nitrogen double bond of iminium salts are analogous to nucleophilic reactions at the carbonyl group of aldehydes and ketones. This is why free enamines do not react with nucleophilic reagents, whereas their salts can undergo such reactions. 

The intermediate formation of iminium salts is postulated in the reduction of (x-amino ketones by the Clemmensen method, occurring with concomitant ring enlargement or contraction (244-246). Reduction of l,2,2-trimethyl-3-piperidone (154) in this manner gave l-methyl-2-iso-propylpyrrolidine (155). 

Iminium ions bearing an electron-withdrawing group bonded to the sp carbon of the iminium function are very reactive dienophiles. Thus, iminium ions 26 generated from phenylglyoxal (Scheme 6.15, R = Ph) or pyruvic aldehyde (R = Me) with methylamine hydrochloride, react with cyclopenta-diene in water at room temperature with good diastereoselectivity [25] (Scheme 6.15). If glyoxylic acid is used, the formation of iminium salt requires the free amine rather than the amine hydrochloride. 

Although some examples of C-substitutions of silylated Schiff bases and iminium salts, in particular the formation of / -lactams, have already been mentioned in Sections 5.1.3 and 5.1.5 (cf. also C-substitutions of lactones and amides in Section 4.8) in this section several additional and typical C-substitutions of 0,0- and 0,N-acetals and of iminium salts derived from carbonyl groups are discussed. 

A. Photoinduced Electron Transfer Chemistry of Iminium Salts. 710... 

Quaternary ammonium cyanoborohydrides have been used for the reduction of iminium salts [14] and in the reductive amination of aldehydes and ketones [15]. 

Appropriate activation of carboxyl groups enables reduction of aliphatic carboxylic acids to the corresponding aldehydes. The electroreduction of iminium salts prepared from aliphatic carboxyKc... 

Scheme 87 Alkaloid-type compounds by reductive alkylation of iminium salts.

The electroreduction of iminium salts in the presence of alkyl halides has been applied to the synthesis of alkaloid-type compounds as depicted in Scheme 87 [127,128]. 

Calculations of simple model Mannich reactions have focused on the role of iminium salt as potential Mannich reagent. ... 

Irradiation of matrix-isolated imidazole-2-carboxylic acid gave the 2,3-dihydro-imidazol-2-ylidene-C02 complex (31) characterized by IR spectroscopy and calculated to lie 15.9 kcal mol above the starting material. A series of non-aromatic nucleophilic carbenes (32) were prepared by desulfurization of the corresponding thiones by molten potassium in boiling THF. The most hindered of the series (32 R = Bu) is stable indefinitely under exclusion of air and water and can be distilled without decomposition. The less hindered carbenes slowly dimerize to the corresponding alkenes. Stable aminoxy- and aminothiocarbenes (33 X = O, S) were prepared by deprotonation of iminium salts with lithium amide bases. The carbene carbon resonance appears at 260-297 ppm in the NMR spectrum and an X-ray structure determination of an aminooxycarbene indicated that electron donation from the nitrogen is more important than that from oxygen. These carbenes do not dimerize. 

From the foregoing discussion, it is clear that DPM rearrangements are very general for a variety of 1,4-unsaturated systems, such as, 1,4-dienes, (3,7-unsaturated aldehydes and ketones, and different 1-aza-1,4-diene derivatives. Surprisingly, the literature was devoid of studies describing the photoreactivity of the closely related 2-aza-1,4-diene derivatives. For many years, the only studies in this area were carried out by Mariano and his co-workers [60] on the photochemistry of iminium salts derived from 2-aza-1,4-dienes. The results obtained demonstrated the synthetic utility of the photocyclizations of iminium salts to different heterocycles, in reactions that are initiated by intramolecular single electron transfer [60]. 

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