Reactions of Imines and Iminium Ions

Imines and iminium ions are nitrogen analogs of carbonyl compounds, and they undergo nucleophilic additions like those involved in aldol condensations. The reactivity order is C=NR C=0 [C=NR2] [C=OH]. Because iminium ions are more reactive than imines, condensations involving imines are frequently run under acidic conditions where the imine is protonated. 

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SECTION 2.2. ADDITION REACTIONS OF IMINES AND IMINIUM IONS... 

The direct observation of this reaction is difficult because of the small equilibrium constant for imine formation. This type of reaction is therefore commonly studied by trapping the imine as it is formed with hydroxylamine, which reacts rapidly to form an oxime. Because the equilibrium constant for formation of the imine between methyl amine and acetone is so small, the equilibrium is established very rapidly. (The observed rate constant for a reaction proceeding to an equilibrium position is larger than the first-order rate constant for the forward reaction [7].) Thus the addition of methylamine and acetone to an aqueous solution results in the establishment of an equilibrium concentration of imine (and iminium ion) in several seconds. In several studies described below wherein reactions subsequent to imine formation occur, it is common to find a presumption of rapid imine equilibria prior to the slower o-proton abstraction or decarboxylation events that occur subsequently. 

A -Methyleneamine equivalents can be generated from 1,3,5-trisubstituted hexahydro-1,3,5-triazines in the presence of a Lewis acid (LA) and used for aminomethylation reactions with various nucleophiles at the -position of amines (Scheme 16). A -Methyleneaniline equivalents, as shown by 110 and 111, result from the breaking of all three carbon-nitrogen bonds of l,3,5-triphenylhexahydro-l,3,5-triazine 109. They have characteristics of imine and iminium ions similar to Mannich bases and can be used for various aminomethylation reactions. However, there have been no reports of using A -methyleneamine equivalents as azadienes, which may react with olefins via [47t-F2Jt] cycloaddition to afford 1,2,3,4-tetrahydroquinolines 112 <2000T5259>. 

A variety of double bonds give reactions corresponding to the pattern of the ene reaction. Those that have been studied from a mechanistic and synthetic perspective include alkenes, aldehydes and ketones, imines and iminium ions, triazoline-2,5-diones, nitroso compounds, and singlet oxygen, 10=0. After a mechanistic overview of the reaction, we concentrate on the carbon-carbon bond-forming reactions. The important and well-studied reaction with 10=0 is discussed in Section 12.3.2. 

Reactions of Ally I and Propargyl/Allenic Organometallics with Imines and Iminium Ions... 

Reactions of Allyl and PropargyUAllenic Organometallics with Imines and Iminium ions 989... 

Reactions ofAllyl and Propargyl/Allenic Organometallics with Imines and Iminium Ions 993 Table IS Reaction of Propargyl/Allenyl Organometallic Reagents (59) with Imines (60 Equation 14)... 

R. A. Batey in Boronic acids preparation and applications in organic synthesis and medicine (D. Hall, Ed.). Wiley-VCH Verlag GmhH, Weinheim, Germany, 2005, pp. 279-304. NucleophUic addition reactions of aryl and alkenylboronic acids and their derivatives to imines and iminium ions. 

The Exterior Frontier Orbital Extension (EFOE) model has been applied to predict r-facial selectivity in nucleophilic additions to imines and iminium ions of the cyclohexanone, tropinone, and adamantan-2-one systems." A review of the EFOE model," and other references to its use, are described later under Regio-, Enantio-, and Diastereo-selective Aldol Reactions. 

A direct asymmetric reductive Mannich-type reaction that allows for the formation of three contiguous stereocentres with high chemo-, diastereo-, and enantio-selectivity (10 1 to 50 1 dr, 96-99% ee ) has been presented (Scheme 4). The reaction commences with the formation of the corresponding iminium ion from aldehyde (122) and prolinol (g) catalyst (125), followed by conjugate reduction with Hantzsch ester (123) to generate an enamine, which then undergoes Mannich reaction with imine (124) to produce (126).179... 

A similar approach to the synthesis of tetracyclic indole alkaloid derivatives has been described [182], and the use of reactive chiral iminium ions allows the realisation of stereoselective aza Diels-Alder reactions even in aqueous solution [183,184]. Nevertheless it should be noted that reactions of electron-rich dienes with imines e. g. derived from amino acids do not necessarily proceed via a Diels-Alder mechanism. They may as well undergo a domino-Mannich-Michael sequence which also efficiently leads to useful nitrogen heterocycles [185-188]. 

Instead of alkyl halides other electrophiles, such as imines or iminium ions, are also used for the nucleophilic attack of enolates. Primary amines react with aldehydes and ketones to produce imines °. For example, the reaction of acetophenone with methyl amine gives... 

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