Reactivity, of imines

It is well known that aziridination with allylic ylides is difficult, due to the low reactivity of imines - relative to carbonyl compounds - towards ylide attack, although imines do react with highly reactive sulfur ylides such as Me2S+-CH2-. Dai and coworkers found aziridination with allylic ylides to be possible when the activated imines 22 were treated with allylic sulfonium salts 23 under phase-transfer conditions (Scheme 2.8) [15]. Although the stereoselectivities of the reaction were low, this was the first example of efficient preparation of vinylaziridines by an ylide route. Similar results were obtained with use of arsonium or telluronium salts [16]. The stereoselectivity of aziridination was improved by use of imines activated by a phosphinoyl group [17]. The same group also reported a catalytic sulfonium ylide-mediated aziridination to produce (2-phenylvinyl)aziridines, by treatment of arylsulfonylimines with cinnamyl bromide in the presence of solid K2C03 and catalytic dimethyl sulfide in MeCN [18]. Recently, the synthesis of 3-alkyl-2-vinyl-aziridines by extension of Dai s work was reported [19]. 

Another interesting example of metal-directed chemistry involving the stabilisation and reactivity of imines is seen in the reaction of pyridoxal with amino acids. This reaction is at the basis of the biological transamination of amino acids to a-ketoacids, although the involvement of metal ions in the biological systems is not established. The reaction of pyridoxal (5.27) with an amino acid generates an imine (5.28), which is stabilised by co-ordination to a metal ion (Fig. 5-55). 

Thus, a new type of Lewis acid, lanthanide triflates, is quite effective for the catalytic activation of imines, and has achieved imino Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between aldehydes, amines, and dienes or alkenes were successfully carried out by using Ln(OTf)3 as catalysts to afford pyridine and quinoline derivatives in high yields. The triflates were stable and kept their activity even in the presence of water and amines. According to these reactions, many substituted pyridines and quinolines can be prepared directly from aldehydes, amines, and dienes or alkenes. A stepwise reaction mechanism in these reactions was suggested from the experimental results. 

With catalysis of Cu(OTf)2 reactivity of imines toward attack by RZnBr is shown to be enhanced by attaching a 2-pyridinesulfonyl group to the nitrogen atom, as in 1 ... 

Thus, this new type of Lewis acid, the Ln(OTf)3, is quite effective for the catalytic activation of imines, and has achieved aza Diels-Alder reactions of imines with dienes or alkenes. The unique reactivities of imines which work as both dienophiles and azadienes under certain conditions were also revealed. Three-component coupling reactions between... 

The photoreduction of imines is not as well understood as that of carbonyl compounds. Padwa et a/. 9 have suggested that the low reactivity of imines towards hydrogen abstraction may be a result of twisting about the C=N bond, which leads to rapid radiationless decay of excited imine. Such a process cannot be the only factor involved, because the cyclic imine (31),70 where syn-anti isomerization is prohibited, only shows reactivity comparable with that of the acyclic imine iV-benzyl i denecyclohexylamine.69 It is also reported that the cyclic imines (33) and (34) undergo photoreduction in propan-2-ol to... 

The di-imine (287), obtained by base-catalysed ring-contraction of (286) (see p. 271), condenses with o-phenylenediamine, giving the imidazolo-quinoxaline (288) in 95% yield (Scheme 113). This is another example of the greater reactivity of imines over carbonyls in the synthesis of 1,4-diazines, as the analogous trioxoimidazole gives a spiro-compound with o-phenylenediamine. ... 

Yamamoto and coworkers [3], however, have reported that reactions of al-lyl-9-BBN with certain chiral imines give the corresponding allylation products with very high enantiomeric excess, in essentially, the quantitative yields (Eq. 12.2). Table 12.1 summarizes these very high 1,2-asymmetric inductions. The main reason for poor selectivity of imine is the complex reactivity of imines toward other organometallic compounds [4-6]. 

In addition to the above equihbrium considerations, kinetic studies also have been used to elucidate the relative reactivities of imines. The effect of electron withdrawal and donation on the reactivity of the azomethine linkage has been found by investigating the rates of hydrolysis of several meta- and ara-substituted diphenyl ketimines. A plot of the logarithms of the rate constants of hydrolysis versus Hanunett sigma constants gives a p value of 2-00 . The positive p value indicates that the reactivity of the azomethine linkage is increased by electron-withdrawing substituents while substituents capable of electron donation decrease its reactivity. 

The supremacy of MCRs is illustrated by excellent atom economy, step efficiency, and mild reaction conditions. Many of the MCRs utilize the reactivity of imines by in situ condensation of (chiral) amines on carbonyls. Furthermore, frequent use of unconventional isocyanide groups, in, for example, the Ugi MCR, is characteristic. More interesting features of the MCR strategy will be addressed in further detail in due course. 

The next important class comprises non-isocyanide-based MCRs. In contrast to IMCRs, non-isocyanide-based MCRs do not rely on the unique properties of isocyanides, but rather rely in most cases on the reactivity of imines generated in situ from amines and aldehydes. This class includes the Gewald reaction [4], the Hantzsch reaction [6], the Biginelli reaction [3], the Petasis reaction [47 9], the Kabachnik-Fields reaction [8, 9], the Povarov reaction [50], and the Doebner reaction [51]. 

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