Aldimines competition reaction

The same catalyst is also effective in three-component reactions between aldehydes, amines, and silylated nucleophiles, leading to amino ketone, amino ester, and amino nitrile derivatives, respectively (Eq. 30) [114]. It is reported that 103 can be recovered and that continuous use is possible without any loss of activity. More interestingly, in competitive reaction of aldehyde, aldimine and silyl enolate, the less reactive aldimine reacted exclusively with silyl enolate in the presence of 103. This unique selectivity was explained by the polymer effect [115]. 

Scheme 10. A competition reaction between an aldehyde and an aldimine...

Table 13.15 Competition reaction of aldehydes and aldimines with TMSCN...

The preparation of optically active analogues of the natural amino acids has proven reasonable using the reaction of tris(trimethylsilyl) phosphite with chiral aldimines prepared from optically active amines.225 The asymmetric induction has been observed to be as high as 80%, a significant competitive process compared to the multistep approaches available.226227 An alternative one-step approach involving asymmetric induction upon addition to an aldimine derived from a chiral N-substituted urea provided a product with less desirable optical purity.228... 

The mechanism for the formation of secondary amine, proposed by von Braun et al., is supported by the fact that the formation of secondary amine decreases with addition of ammonia.11,12 Ammonia may add to the aldimine 1 competitively with primary amine, forming a,a-diamine 6 (eq. 7.12), and thus may suppress the condensation reaction leading to secondary amine formation (eqs. 7.5 and 7.6). Further, in the presence of ammonia, the intermediates 2 and 3 may be decomposed to give one mole of aldimine and one mole of primary amine by the reversal of the reactions in eqs. 7.5 and 7.613,14 and may thus effectively depress the formation of secondary amine. 

Rees and co-workers have carried out an extensive study of the addition of tri-methylsilyloxy phosphorus(lll) derivatives (phosphites, phosphonites, and phos-phinites, generated in situ) to aldimines to yield a-aminoalkyl-phosphonates, phosphinates and phosphine oxides (respectively, the transferred /V-TMS group being lost during work-up). Competition experiments demonstrated that the addition to imines is faster than that to the parent aldehydes. They found that the presence of electron-withdrawing groups in the imine slows the reaction. 

Imines and their derivatives could be used in an analogous way to aldehydes, ketones, or their derivatives this subject has been reviewed [79]. A competition experiment between an aldimine and the corresponding aldehyde in the addition to an enol silyl ether under titanium catalysis revealed that the former is less reactive than the latter (Eq. 14) [80]. In other words, TiCU works as a selective aldehyde activator, enabling chemoselective aldol reaction in the presence of the corresponding imine. (A,0)-Acetals could be considered as the equivalent of imines, because they react with enol silyl ethers in the presence of a titanium salt to give /5-amino carbonyl compounds, as shown in Eqs (15) [81] and (16) [79,82]. 

The addition of organometallic agents to aldimines and ketimines provides a useful route to substituted amines, although this reaction is sensitive to imine/organometallic substitution. Along with addition, competitive enolization, reduction and bimolecular reduction (coupling) reactions are also possible. 

In the final analysis, it appears that the diastereoselectivity of the reactions of imines and crotylboranes (47, 96) depends on the relative rates of crotyl transfer e.g. 95a —> 93) versus imine isomerization that leads to competitive pathways (e.g. 94d - 92). When R is an aryl group, the rate of crotyl transfer is probably faster than competitive imine isomerization. When R is an alkyl group, however, the relative rates are probably inverted. The driving force for imine isomerization is probably that complex (95a) is not very stable owing to the bulky 9-BBN unit positioned syn to R, while the complex of crotyl-9-BBN (47) and a (Z)-aldimine e.g. 94d) is probably much more stable. It is conceivable, therefore, that the overall rate of reaction via (94d) can be much faster than via (95a) even though the (Z)-imine cannot be detected in solution. Additional research is clearly needed to clarify the stereochemical course of these reactions. 

A different situation is observed in the case of M. tuberculosis D-Ala forms the external aldimine, either, but also, slowly, the first quinonoid intermediate. It is claimed that this form reacts with pimeloyl-CoA to give d-AOP. However, the characteristics of the reference synthetic AOP are those of the racemic compound, as already discussed." Thus, this reaction with D-Ala should be reinvestigated. It was also reported that D-Ala inhibits the reaction with L-Ala however, the inhibition is no longer competitive, but of the linear mixed type, which would mean that the two enantiomers bind independently at different sites. 

The possibility of aldimine isomerization before cyclization is consistent with experimental observation when the cyclization is viewed as occurring by nucleophilic attack of the ketene enolate on the aldiminium ion in the zwitterionic intermediate. The effects of electron-donating and electron-withdrawing substituents in the ketene and aldimine as well as steric effects may be understood in terms of this model. Thus the stereochemical outcome of the Staudinger reaction is determined by the competition between direct ring closure of the zwitterion and isomerization of the aldimine. 

Cyclopentanone and cyclohexanone can also be determined in complex mixtures by using the formation of ketimines, from 20 per cent solutions of hexamethylenediamine, at a pH above j2.(4oi>) The aldehydes, when present, give aldimine waves at potentials about 0-2 V more positive than the ketimine waves. However, moderate concentrations of aldehydes do not interfere in the determination of ketones as (at the concentrations of hexamethylenediamine used) a substantial part of the aldimine is converted into a polarographically inactive compound which, during the course of the reaction, is competitive to the aldimine formation. For the determination of aldehydes, a 2 per cent solution of hexamethylenediamine proved to be the most suitable. 

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