Amines azomethine imines

As the sp nitrogen atom in many heterocycles can be alkylated and aminated, the construction of an azomethine ylide or azomethine imine dipole is readily attainable as shown in Scheme 13. These ylides are very reactive and undergo cycloaddition with a... 

Chen extended the scope of his iminium ion catalysed [3+2] cycloaddition with azomethine imines (see Sect. 2.1.2) to encompass cyclic a,P-unsaturated ketone substrates using primary amine 147 as the catalyst [194]. Interestingly, the presence... 

Similar to those of oxygen and sulfur ylide, ammonium ylide or azomethine ylide can be generated by the interaction of metal carbene and amine or imine, respectively. As is the case of sulfur, nitrogen also has a strong coordinating ability to a metal complex. Consequently, metal complex-catalyzed diazo decomposition in the presence of an amine or imine usually requires high reaction temperatures (Figure 6). 

A convenient one-step transformation of primary and secondary amines into the corresponding unprotected guanidines using 4-benzyl-3,5-dimethyl-l/f-pyrazole-l-carboxamidine 90 and its polymer-bound variant were described <06S461>. 1,3-Dipolar cycloaddition of polymer-bound alkynes to azomethine imines generated in situ from N-aminopyridine iodides followed by aromatization of the cycloadducts gave polymer-bound pyrazolopyridines that were released from the resin as carboxylic acids with trifluoroacetic acid or as methyl esters with sodium methoxide <06JCO344>. 

Amine Ar-imines are derived formally from tertiary amines by replacing the free pair of electrons by an imino group. Aliphatic, aromatic, or heteroaromatic compounds are obtained according to the nature of the amine. Heteroaromatic JV-imines are derived from heterocyclic compounds containing an azomethine nitrogen atom in the molecule. 

The action of ammonia or primary amines and hydroxylamine-(9-sulfonic acid upon ketones also yields diaziridines. Likewise, the amination of imines (azomethines) with hydroxylamine-O-sulfonic acid yields diaziridines ... 

In 2006 Chen et al. [128] reported the first organocatalyzed stereoselective [3 + 2] dipolar cycloaddition of azomethine imines with aliphatic a,p-unsaturated aldehydes using chiral secondary amine catalyst 59. The desired cycloaddition products were obtained with good yields, good diastereoselectivities and good enantioselectivities for both electron-rich and electron-poor aromatic azomethine imines. In contrast, aliphatic azomethine imines (R = -Pr) led to poorer results (40% yield and 77% ee). Investigation of a variety of solvents and additives revealed that tetrahydrofurane/HaO mixture and 10 mol% of trifluoroacetic acid were preferred. No reaction was observed when aromatic a,p-unsaturated aldehydes were used. The authors proposed an iminium ion mechanism that could proceed via the transition states shown in Scheme 11.47. 

A year later, based on the same principle by using primary amine-catalyzed iminium ion activation in combination with external Brpnsted acid additives, Chen et al. [129] were able to achieve the asymmetric 1,3-dipolar cycloaddition of cyclic enones and a variety of azomethine imines in excellent yields and selectivities (Scheme 11.48). In this case, to scavenge the generated H2O during the formation of the enamine nucleophile intermediate, and to overcome the expected hydrogenbonding interaction, a stoichiometric amount of molecular sieves (4 A) was added. Interestingly, when the pseudoenantiomer catalyst 61 was employed, an opposite enantiomer of the product was formed in good yields and selectivities. 

Finally, a direct Mannich-type approach has been developed for the enantioselective synthesis of hydrazines and amines (Scheme 16.40). Thus, by trapping with alkyl diazoacetates some in s/iw-generated acyclic azomethine imines, in the presence of axially chiral dicarboxylic acids, a series of a-diazo-(3-hydrazino esters were obtained with excellent enantioselectivities [86]. 

Although considerable improvements have been made for endo-selective cycloadditions of azomethine imines, methods for exo and enantioselective cycloaddition of azomethine imines were relatively scarce. By employing novel, multifunctional primary amine catalysts 145 derived from cinchona alkaloids in the presence of triisopropylbenzene sulfonic acid (TIPBA) 146 as cocatalyst, Chen and coworkers developed the first organocatalytic, highly exo-selective, and enantioselective 1,3-DC reaction of cyclic enones 142 and azomethine imines 143 in 2007 [53]. The additional and synergistic hydrogen-bonding interaction of catalyst and 1,3-dipole is essential for enantiocontrol, and excellent stereoselectivities were achieved for a broad scope of substrates (dr > 99 1, up to 95% ee) (Scheme 2.37). 

A stereoselective [3+2] dipolar cycloaddition of azomethine imines 141 with ot,P-unsaturated aldehydes catalyzed by ot,a-diarylprolinol salts was also reported by Chen et al. [88]. More important, they extended the strategy to cyclic enones by employing a Cinchona alkaloid-derived bifunctional primary amine catalyst 142 (Scheme 1.52) [89]. The synergistic hydrogen-bonding interaction of the catalyst and 1,3-dipoles 141 plays a critical role in high enantiocontrol (dr >99 1, up to 95% ee). 

A three-component Ugi-type reaction using A/ -alkylbenzohydrazide (instead of amine) has been catalysed by an axially chiral binaphthyl dicarboxylic acid and found to proceed with up to 93% ee with an acyclic azomethine imine. Stereoselectivity of a Ugi reaction starting from an oxanorbornenone / -amino acid, R CHO, and RNC has been improved through solvent selection. ... 

Asymmetric 1, 3-dipolar cycloaddition is a powerful tool for synthesizing chiral heterocyclopentane compounds. Chen group demonstrated that primary amine 143 derived from cinchona-alkaloid was an effective catalyst for the 1,3-dipolar cycloaddition of a,p-enones and azomethine imines (Schane 5.38) [67], It was proposed that multi-hydrogen-bonding, particularly those between the free OH and the substrate are critical for stereocontrol (Scheme 5.38). The reaction went smoothly with a wide range of substrates with up to 99% yield, 99 1 dr and 95% ee. 

A cornucopia of synthetically useful 1,3-dipoles have been exploited for the preparation of azacycles and amines. One elegant example is the intramolecular cycloaddition of azomethine imines [48] reported by Jacobi in a total synthesis of the shellfish toxin saxitoxin (20, Scheme 18.5) [49]. The acid-catalyzed condensation of hydrazines and acetals is a mild method for the generation of azomethine imines [50]. In the key cyclization event, the inter-... 

An azomethine imine cyclization is found in Overman s construction of hexacycle 26 (Scheme 18.6) [51, 52]. The approach involved in situ formation of azamethine imine 23 with the aid of thiosemicarbazide (22), followed by dipolar cycloaddition and condensation. Product 25 was subsequently converted into 26, which served to confirm the revised structure of trans-fused palau amine (27) [52],... 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

The nitrogen analogs of ketones and aldehydes are called imines, azomethines, or Schiff bases, but imine is the preferred name and we use it here. These compounds can be prepared by condensation of primary amines with ketones or aldehydes.102 The equilibrium constants are unfavorable, so the reaction is usually driven forward by removal of water. 

Aryl alkyl amines gave hydroxylamine 0-arylsulfonates when reacted with arylsul-fonyl peroxide. The products were later decomposed to azomethine and further hydrolysis results in the corresponding amine with one less carbon atom. Thus when p-methoxy-benzylamine was treated with p-nitrophenylsulfonyl peroxide at —78 °C in ethyl acetate, p-methoxybenzaldehyde and p-methoxyaniline were obtained . Cyclic amines with p-nitrophenylsulfonyl peroxide were converted to the Al-(p-nitrophenylsulfonyloxy)amine derivatives, which further rearranged to ring-expanded cyclic imines in good yields (equation 9 f. ... 

The individual steps are (a) the anodically formed nickel oxide hydroxide dehydrogenates the amine to an imine (b) the imine is further dehydrogenated to the nitrile (c) competing with the second dehydrogenation are the hydrolysis of the imine to an aldehyde and its further oxidation to an acid or (d) the condensation with the starting amine to form an azomethine. 

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