Salts and Neutral Imines

Cycloadditions of iminium compounds with 1,3-dienes to afford Diels-Alder adducts seems to be a reaction of general applicability. On the other hand, simple electron-rich imino species are less reliable dienophiles. Some electron-rich imines will undergo Diels-Alder reactions under acid catalysis and thus are probably actually reacting as iminium salts. However, inverse electron demand [4 -I- 2] cycloadditions of neutral imines with electron-deficient dienes have been reported, as have additions to exceptionally reactive dienes inde infra). 

Bohme et al. described the initial example of a [4 + 2] cycloaddition of an iminium salt [Eq. (9)].  

In this case, an a-haloamine was used to generate the iminium dienophile in situ. 

In a related series of reactions, Babayan et al. found that aminals, on treatment with acetyl chloride, generated iminium chlorides which could be trapped with isoprene to give Diels-Alder adducts [Eq. (10)]. 

The adducts themselves were not isolated but were fragmented with base to afford amino-substituted dienes in mediocre yields. 

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One possible explanation is provided by considering the probable reactive intermediates involved fragmentation of 25 with effective loss of a benzotriazole anion must necessarily give rise to a reactive, and therefore less selective, iminium salt, while concomitant proton loss from 23 or 24 could give rise to a less reactive neutral imine by similar, but more facile, fragmentation. 

Preparative Methods (i) preparation of racemic DPEN and its optical resolution Reaction of benzil and cyclohexanone in the presence of ammonium acetate and acetic acid at reflux temperature gives a cyclic bis-imine (1) (eq 1). Stereoselective reduction of the bis-imine with lithium in THF-liquid ammonia at —78 °C followed by addition of ethanol, then hydrolysis with hydrochloric acid and neutralization with sodium hydroxide produces the racemic diamine (2). Recrystallization of the l-tartaric acid salt from a 1 1 water-ethanol mixture followed by neutralization with sodium hydroxide, recrystallization from hexane results in (5,5)-DPEN (3) as colorless crystals. 

The ability to reduce compounds under acidic conditions is ideal for the reduction of enamines. Protonation of nitrogen gives an iminium salt in acidic media that is then reduced with cyanoborohydride to an amine.Imines can be reduced in acidic media in the presence of many other functional groups, as shown by Cook s reduction of imine 165 to give 166 in 79% yield in a synthesis of substituted tetrahydro-P-carbolines. 2 This reagent is excellent for the reduction of iminium salts at neutral pH as well,l 3 and it is also useful for the reductive alkylation of amines. Dimethylamino derivatives such as 168 can be prepared from the amine (167 in this case) by treatment with formaldehyde and cyanoborohydride, even in the presence... 

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. 

Similar aza-Diels-Alder reactions of Danishefsky s diene with imines or aldehydes and amines in water took place smoothly under neutral conditions in the presence of a catalytic amount of an alkaline salt such as sodium triflate or sodium tetraphenylborate to afford dihydro-4-pyridones in high yields (Eq. 12.49).117 Antibodies have also been found to catalyze hetero-Diels-Alder reactions.118... 

The TEAF system can be used to reduce ketones, certain alkenes and imines. With regard to the latter substrate, during our studies it was realized that 5 2 TEAF in some solvents was sufficiently acidic to protonate the imine (p K, ca. 6 in water). Iminium salts are much more reactive than imines due to inductive effects (cf. the Stacker reaction), and it was thus considered likely that an iminium salt was being reduced to an ammonium salt [54]. This explains why imines are not reduced in the IPA system which is neutral, and not acidic. When an iminium salt was pre-prepared by mixing equal amounts of an imine and acid, and used in the IPA system, the iminium was reduced, albeit with lower rate and moderate enantioselectivity. Quaternary iminium salts were also reduced to tertiary amines. Nevertheless, as other kinetic studies have indicated a pre-equilibrium with imine, it is possible that the proton formally sits on the catalyst and the iminium is formed during the catalytic cycle. It is, of course, possible that the mechanism of imine transfer hydrogenation is different to that of ketone reduction, and a metal-coordinated imine may be involved [55]. 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

Nitriles having at least one hydrogen on the functional carbon, react with trimethylchlorosilane under electrochemical conditions to provide a mixture of silazanes and enamines of acylsilanes. These enamines have been suggested to be formed from the isomeric ketene imine form of the nitrile. They were obtained as a mixture of Z (major) and E isomers. Treatment of the silazane-enamine mixture with trimethylchloro-silane/methanol and sodium borohydride followed by neutralization of the salt gives the corresponding RSMA.191... 

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