Imine compounds nucleophile reactions

Perfluorinated carbonyl compounds, especially hexafluoroacetone, are highly electron-deficient species and react vigorously with a wide variety of HX nucleophiles The reaction of these ketones and of most polyfluonnated imines toward nucleophiles can be generahzed by the scheme shown m equation 1... 

In spite of the steric and electronic differences, the nucleophilic addition of enolates to imines (aza aldoi reaction) proceeds probably through similar pericyclic transition states as the carbonyl compounds do. 

Aziridines have been synthesized, albeit in low yield, by copper-catalyzed decomposition of ethyl diazoacetate in the presence of an inline 260). It seems that such a carbenoid cyclopropanation reaction has not been realized with other diazo compounds. The recently described preparation of 1,2,3-trisubstituted aziridines by reaction of phenyldiazomethane with N-alkyl aldimines or ketimines in the presence of zinc iodide 261 > most certainly does not proceed through carbenoid intermediates rather, the metal salt serves to activate the imine to nucleophilic attack from the diazo carbon. Replacement of Znl2 by one of the traditional copper catalysts resulted in formation of imidazoline derivatives via an intermediate azomethine ylide261). 

In addition to using amine oxidation products as mediators, anodic oxidation reactions can be used to functionalize amine compounds. These reactions include both - examples that generate imines and nitriles, as well as examples that lead to the addition of nucleophiles to the carbon alpha to the nitrogen. 

The typical behavior of enamines has been mainly observed for compounds possessing a tertiary nitrogen atom.1 The analogous derivatives with a secondary amino group (the a,j8-unsaturated secondary amines) could, in principle, possess either the imino or the tautomeric enamine structure, but the first possibility is preferred practically without exception. In the text, some examples of their properties are quoted for the sake of comparison with those of tertiary enamines on these occasions, the group designation imines is used. Nucleophilic reactions of a limited number of aromatic heterocyclic systems are also included when they are similar to the reactions of enamines and illustrate the specific character of the enamine grouping. 

Nucleophilic Reactions of Aromatic Heterocyclic Bases Heterocyclic aromatic compounds containing a formal imine group (pyridine, quinoline, isoquinoline, and acridine) also react readily with nucleophilic reagents. A dihydro-derivative results, which is readily dehydrogenated to a new heteroaromatic system. Since the nucleophile always attacks the a-carbon atom, the reaction formally constitutes an addition to the C=N double bond. An actual localization of the C=N double bond in aromatic heterocyclic compounds is incompatible with molecular orbital theory. The attack of the nucleophilic reagent occurs at a site of low 77-electron density, which is not... 

Ethyleneimine (aziridine) and carbon-substituted alkyleneimines are relatively weakly basic compounds [43, 44], This is ascribed to 71-electron delocalization in the ring [44]. By protonation of the imine cycle this aromaticity disappears, and iminium rings are much more readily broken than imines [45], Also the N-alkylethyleneimines are only weakly basic, and they are also more resistant to ring-opening nucleophilic reactions [46]. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Recent studies have shown that coordinated ammonia and amine ligands under basic conditions may effect nucleophilic attack at carbonyl centres in organic compounds, " These reactions occur due to formation of deprotonated amido species which can act as nucleophiles. For example, reaction of cobalt(III) and platinum(IV)ammines with ketones gives the corresponding Co and Pt imine complexes. A similar reaction between [Ru(NH3)6] and diones produces the corresponding Ru diimine (108). It has also been found that nitrilepentaammineruthenium(II)... 

The reactivity of hydrazidoyl halides in nucleophilic reactions, as well as the ready elimination of hydrogen halides to afford the highly reactive nitrile imines renders this class of compounds quite useful in organic synthesis. 

Lewis Acid Promoted Addition Reactions of Organometallic Compounds Nucleophilic Addition to Imines and Imine Derivatives Nucleophilic Addition to Carboxylic Acid Derivatives... 

Secondary amines cannot form imines, and dehydration proceeds to give carbon-carbon double bonds bearing amino substituents (enamines). Enamines were mentioned in Chapter 7 as examples of nucleophilic carbon species, and their synthetic utility is discussed in Chapter 1 of Part B. The equilibrium for the reaction between secondary amines and carbonyl compounds ordinarily lies far to the left in aqueous solution, but the reaction can be driven forward by dehydration methods. 

The addition of primary amines to fluoroolefins under anhydrous conditions yields imines The hexafluoropropene dimer, perfluoro-2-methyl-2-pcntcne, and ten butylamine react to yield a mixture of two compounds m a 9 4 ratio [4] (equation 3) rather than just the major keteiiimme-imine, as previously reported [5] It IS claimed that this result is possible by means of isomerization to the terminally unsaturated difluoromethylene isomer prior to nucleophilic attack Secondary amines add to fluoroolefins under anhydrous conditions to give fluonnated ternary amines m good yields If the fluoroolefin is added to the amine without cooling the reaction mixture, or if an excess of the secondary armne is used, there is a tendency toward dehvdrofluonnation of the ternary amine The products... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

The early stages of the reaction of the quaternary salt can be regarded as proceeding in a manner exactly analogous to that by which the isoxazoles themselves are degraded, the j8-oxoketene imine structure (148) being one mesomeric form of a compound which could alternatively be formulated as a nitrilium betaine. However, by contrast with the products from the isoxazoles (i.e., enolates of /3-keto-nitriles), this is electrically neutral and susceptible to further nucleophilic attack. 

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