Subject reaction with iminium salts

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... 

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). 

In the total synthesis of reserpine, Woodward and collaborators (10) have reported that the quaternary iminium salt J8 was reduced with aqueous metha-nolic sodium borohydride to methyl 0-acetyl isoreserpate 09). This is the anticipated product whether the stereochemical sense of the reaction is subject to steric or thermodynamic control as pointed out by Woodward. It is also the expected one on the basis of stereoelectronic control. 

A 4-bond synthesis of pyridines from carbonyl compounds, which were subjected to Vilsmeier-Haack conditions giving the conjugated iminium salts, has been achieved by reaction with ammonium acetate (Scheme 113)... 

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. 

Vilsmeier formylation of 2-benzylisoindole gives the 1-formyl derivative (61%).25 With 1-phenylisoindole reaction occurs at the unsubstituted a-position the intermediate iminium salt on neutralization gives the cross-conjugated enamine system 78, which has been isolated and characterized. X-Ray analysis confirms the assigned structure.95 On hydrolysis, the formyl derivative, which has also been the subject of X-ray crystal analysis (Figs. 4 and 5), is formed. As expected from the analogy with pyrrole chemistry, the aldehyde does not readily form typical carbonyl derivatives. 

A related example disclosed recently by McNulty et al. is a one-pot Wittig reaction of aldehydes with phosphonium salts in the presence of 10 mol% of morpholine, L-proline or p-toluenesulfonamide and 2.0 equiv. of NaHCOs (Scheme 55) [227]. This reaction gives high E selectivity. A rapid and reversible condensation of the aldehyde with the amine (derivative) catalyst has been proposed to form an iminium or an imine intermediate that is subjected to olefination with the in situ generated phosphonium ylides, though a base-catalyzed pathway is not ruled out. It has been confirmed that an N-sulfonyl imine can be formed quantitatively from the corresponding aldehyde and sulfonamide under the reaction conditions. 

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